What is antacid medicine

Antacids are medicines that counteract (neutralize) the acid in your stomach to relieve indigestion and heartburn. Antacids help to treat heartburn (indigestion). Antacids come as a liquid, powder or chewable tablets. Liquid antacid works faster, but you may like tablets because they are easy to use. You can buy many antacids without a prescription from pharmacies and shops.

All antacids work equally well, but they can cause different side effects. If you use antacids often and have problems with side effects, talk with your health care provider.

Common types of antacids

Many different types of antacid are available. Some are sold under a brand name and others are named after their main ingredient.

Antacid ingredients to look for include:

• Aluminium hydroxide
• Magnesium carbonate
• Magnesium trisilicate
• Magnesium hydroxide
• Calcium carbonate
• Sodium bicarbonate

Some antacids also contain other medicines, such as an alginate (which coats your gullet with a protective layer) and simeticone (which reduces flatulence).

Antacids are made with 3 basic ingredients. You may have side effects from taking antacids. If you have problems, try another brand.

• Brands with magnesium may cause diarrhea.
• Brands with calcium or aluminum may cause constipation.
• Rarely, brands with calcium may cause kidney stones or other problems.
• If you take large amounts of antacids that contain aluminum, you may be at risk for calcium loss, which can lead to weak bones (osteoporosis).

Antacids can change the way your body absorbs the other medicines you are taking. It is best to take any other medicine either 1 hour before or 4 hours after you take antacids.

Sodium bicarbonate

Sodium bicarbonate comes as a tablet and powder to take by mouth. Sodium bicarbonate is taken one to four times a day, depending on the reason you take it. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take sodium bicarbonate exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are using sodium bicarbonate as an antacid, it should be taken 1 to 2 hours after meals, with a full glass of water. If you are using sodium bicarbonate for another reason, it may be taken with or without food. Do not take sodium bicarbonate on an overly full stomach.

Dissolve sodium bicarbonate powder in at least 4 ounces (120 milliliters) of water. Measure powdered doses carefully using a measuring spoon.

• Do not use sodium bicarbonate for longer than 2 weeks unless your doctor tells you to. If sodium bicarbonate does not improve your symptoms, call your doctor.
• Do not give sodium bicarbonate to children under 12 years of age unless your doctor tells you to.

What special precautions should I follow?

Before taking sodium bicarbonate:

• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially other antacids, aspirin or aspirin-like medicines, benzodiazepines, flecainide (Tambocor), iron, ketoconazole (Nizoral), lithium (Eskalith, Lithobid), methenamine (Hiprex, Urex), methotrexate, quinidine, sulfa-containing antibiotics, tetracycline (Sumycin), or vitamins. Take sodium bicarbonate at least 2 hours apart from other medicines.
• tell your doctor if you have or have ever had high blood pressure, congestive heart failure, or kidney disease or if you have recently had bleeding in your stomach or intestine.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking sodium bicarbonate, call your doctor.

What special dietary instructions should I follow?

Sodium bicarbonate increases the amount of sodium in your body. If you are on a sodium-restricted diet, check with your doctor before taking sodium bicarbonate.

What should I do if I forget a dose?

If your doctor has told you to take sodium bicarbonate on a certain schedule, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can sodium bicarbonate cause?

Sodium bicarbonate may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• increased thirst
• stomach cramps
• gas

If you have any of the following symptoms, stop taking sodium bicarbonate and call your doctor immediately:

• severe headache
• nausea
• vomit that resembles coffee grounds
• loss of appetite
• irritability
• weakness
• frequent urge to urinate
• slow breathing
• swelling of feet or lower legs
• bloody, black, or tarry stools
• blood in your urine

Aluminum Hydroxide and Magnesium Hydroxide

Aluminum Hydroxide and Magnesium Hydroxide are antacids used together to relieve heartburn, acid indigestion, and upset stomach. Aluminum Hydroxide and Magnesium Hydroxide may be used to treat these symptoms in patients with peptic ulcer, gastritis, esophagitis, hiatal hernia, or too much acid in the stomach (gastric hyperacidity). Aluminum Hydroxide and Magnesium Hydroxide combine with stomach acid and neutralize it. Aluminum Hydroxide, Magnesium Hydroxide are available without a prescription.

Aluminum Hydroxide and Magnesium Hydroxide comes as a chewable tablet and liquid to take by mouth. Chew tablets thoroughly; do not swallow them whole. Drink a full glass of water after taking the tablets. Shake the oral liquid well before each use to mix the medicine evenly. The liquid may be mixed with water or milk.

Follow the directions on the package label or on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Aluminum Hydroxide, Magnesium Hydroxide antacids exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Do not take antacids for more than 1 to 2 weeks unless prescribed by your doctor.

What special precautions should I follow?

Before taking Aluminum Hydroxide and Magnesium Hydroxide antacids:

• tell your doctor and pharmacist if you are allergic to Aluminum Hydroxide, Magnesium Hydroxide antacids or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially aspirin, cinoxacin (Cinobac), ciprofloxacin (Cipro), digoxin (Lanoxin), diazepam (Valium), enoxacin (Penetrex), ferrous sulfate (iron), fluconazole (Diflucan), indomethacin, isoniazid (INH), itraconazole (Sporanox), ketoconazole (Nizoral), levofloxacin (Levaquin), lomefloxacin (Maxaquin), nalidixic acid (NegGram), norfloxacin (Noroxin), ofloxacin (Floxin), sparfloxacin (Zagam), tetracycline (Achromycin, Sumycin), and vitamins. If your doctor tells you to take antacids while taking these medications, do not take them within 2 hours of taking an antacid.
• tell your doctor if you have or have ever had kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking Aluminum Hydroxide, Magnesium Hydroxide antacids, call your doctor.

What special dietary instructions should I follow?

If you are taking this medication for an ulcer, follow the diet prescribed by your doctor carefully.

What should I do if I forget a dose?

If you are taking scheduled doses of Aluminum Hydroxide and Magnesium Hydroxide, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can aluminum hydroxide and magnesium hydroxide cause?

Side effects from Aluminum Hydroxide, Magnesium Hydroxide are not common. To avoid the chalky taste, take with water or milk. Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• constipation
• loss of appetite
• unusual tiredness
• muscle weakness

When to use antacids

Antacids are a good treatment for heartburn that occurs once in a while. Take antacids about 1 hour after eating or when you have heartburn. If you are taking them for symptoms at night, DO NOT take them with food.

Antacids may help if you have:

• Indigestion
• Heartburn or acid reflux – also known as gastro-esophageal reflux disease (GERD)
• Stomach ulcer
• Gastritis (inflammation of the stomach lining)

They can quickly relieve your symptoms for a few hours. But they don’t treat the underlying cause and long-term use isn’t recommended.

Speak to your doctor if you find you need to take antacids regularly.

Antacids cannot treat more serious problems, such as appendicitis, a stomach ulcer, gallstones, or bowel problems.

Talk to your provider if you have:

• Pain or symptoms that do not get better with antacids
• Symptoms every day or at night
• Nausea and vomiting
• Bleeding in your bowel movements or darkened bowel movements
• Bloating or cramping
• Pain in your lower belly, on your side, or in your back
• Diarrhea that is severe or does not go away
• Fever with your belly pain
• Chest pain or shortness of breath
• Trouble swallowing
• Weight loss that you cannot explain

Call your provider if you need to use antacids on most days.

Who may not be able to take antacids

Antacids are safe for most people to take, although they aren’t suitable for everyone.

Speak to a pharmacist or your doctor for advice first if you:

• are pregnant or breastfeeding – most antacids are considered safe to take while pregnant or breastfeeding, but always get advice first
• are looking for a medicine for a child under 12 years of age – some antacids are not recommended for children
• have liver disease, kidney disease or heart failure – some antacids may not be safe if you have one of these problems
• have an illness that means you need to control how much salt (sodium) is in your diet, such as high blood pressure or cirrhosis (liver scarring) – some antacids contain high levels of sodium, which could make you unwell
• are taking other medicines – antacids can interfere with other medications and may need be avoided or taken at a different time

Antacid and pregnancy

Heartburn occurs in up to 80% of pregnant women by the end of the third trimester ¹. Antacids containing aluminum, calcium, or magnesium are often considered first-line treatment in pregnancy. However, at high doses, antacids containing calcium can cause milk-alkali syndrome ² and antacids with aluminum can cause neurotoxicity. Selective histamine H2 blockers (e.g., cimetidine, famotidine, ranitidine) have been used in all trimesters with no known teratogenic effects. In a meta-analysis of 2,398 women taking H2 blockers, the odds ratio (OR) for congenital malformations was 1.14 ³. An odds ratio (OR) is a measure of association between an exposure and an outcome. The odds ratio (OR) represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratio>1 means the exposure is associated with higher odds of outcome. Odds ratio<1 means the exposure is associated with lower odds of outcome. Odds ratio=1 means the exposure does not affect odds of outcome ⁴.

Proton pump inhibitors recently became available OTC (over-the-counter). Although concerns have been raised about the potential teratogenicity of omeprazole (Prilosec), multiple large cohort studies have demonstrated its safety when taken before conception and during the first trimester ⁵. In a meta-analysis of 1,530 infants exposed to proton pump inhibitors, the odds ratio for congenital malformations was 1.12 overall and 1.17 for omeprazole alone, and there was no increased risk of preterm birth or spontaneous abortion ⁶. In another study of proton pump inhibitor use in the first trimester (n = 5,082), the odds ratio (OR) for birth defects was 1.10. Proton pump inhibitors and H2 blockers are considered safe in pregnancy ⁷.

Diarrhea and constipation are common during pregnancy. Products containing bismuth, mineral oil, and castor oil should be avoided. Bismuth itself is safe, but it has the same risks as aspirin when combined with salicylate ⁸. In a study of 89 women, loperamide (Imodium) did not increase the risk of malformation, but was associated with smaller infants ⁹. However, in a later study of 638 women, loperamide had an odds ratio of 1.43 for congenital malformations. Although the American Gastroenterological Association considers loperamide to be low risk, it should be avoided when possible until further information is available ¹⁰. Saline laxatives may cause electrolyte sodium retention and should be used sparingly ¹¹. Polyethylene glycol 3350 (Miralax) has minimal systemic absorption and is considered the drug of choice for chronic constipation despite a lack of research ¹¹. Table 1 summarizes the safety of OTC antacids, antidiarrheals, and laxatives in pregnancy.

Table 1. Safety of Over-the-Counter Antacids, Antidiarrheals, and Laxatives in Pregnancy

Medication	Drug class	Pregnancy risk category*	Crosses the placenta?	Use in pregnancy
Cimetidine (Tagamet)	Selective histamine H2 antagonist	B	Yes	Potential weak antiandrogenic activity (only observed in animal studies)
Famotidine (Pepcid)	Selective H2 antagonist	B	Yes	Limited human data
Nizatidine (Axid)	Selective H2 antagonist	B	Yes	Limited human data
Ranitidine (Zantac)	Selective H2 antagonist	B	Yes	May be preferable to cimetidine for chronic use
Omeprazole (Prilosec)	Proton pump inhibitor	C†	Yes	Most human data suggest it is safe throughout pregnancy
Aluminum hydroxide	Antacid	Not available	Not known	Considered safe in pregnancy; risk of neurotoxicity with high doses
Calcium carbonate	Antacid	Not available	Yes	Drug of choice; risk of milk-alkali syndrome with high doses
Magnesium hydroxide, magnesium carbonate	Antacid	Not available	Not known	Considered safe in pregnancy; magnesium may cause tocolysis in late pregnancy, but this is not a risk with over-the-counter preparations
Simethicone (available as a single agent and contained in multiple combination antacids)	Antiflatulent	C	No	Limited data; not absorbed, so considered safe in pregnancy
Bismuth subsalicylate (Pepto-Bismol)	Antidiarrheal	C	Not known	Insufficient data; should be avoided during pregnancy, especially in the second and third trimesters because it has a salicylate portion‡
Loperamide (Imodium)	Antidiarrheal	C	Not known	Limited human data; questionable association with cardiovascular defects
Mineral oil	Emollient laxative	C	No (not absorbed)	Should be avoided in pregnancy, may interfere with absorption of fat-soluble vitamins§
Castor oil	Laxative/oxytocic	X	Not known	Should be avoided in pregnancy, potential for maternal/fetal morbidity
Polyethylene glycol 3350 (Miralax)	Osmotic laxative	C	Not known	Drug of choice for chronic constipation

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[Sources ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷]

Table 2. U.S. Food and Drug Administration Pregnancy Risk Categories for Medications

Category	Definition
A	Controlled studies in pregnant women fail to demonstrate a risk to the fetus in the first trimester, there is no evidence of risk in later trimesters, and the possibility of fetal harm appears remote.
B	Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
C	Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
D	There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
X	Studies in animals or humans have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience, or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.

Footnote: The Food and Drug Administration (FDA) in 2014 removed the pregnancy categories A, B, C, D, and X from all human prescription drug and biological product labeling ¹⁸. The pregnancy letter categories – A, B, C, D and X will be replaced by a narrative risk summary based on available data. The Food and Drug Administration (FDA) final rule requires that the labeling include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation.

Antacid uses

Check the instructions on the packet or leaflet to see how much antacid to take and how often. This depends on the exact medicine you’re taking.

Antacids should be used when you have symptoms or think you will get them soon – for most people, the best time to take them is with or soon after meals, and just before going to bed.

Remember that doses for children may be lower than for adults.

Contact your doctor or pharmacist if you take too much of the medicine and start to feel unwell.

Taking antacids with food, alcohol and other medicines

It’s best to take antacids with food or soon after eating because this is when you’re most likely to get indigestion or heartburn. However, if you are taking them for symptoms at night, DO NOT take them with food.

The effect of the antacid medicine may also last longer if taken with food.

Antacids can affect how well other medicines work, so don’t take other medicines within two to four hours of taking an antacid.

You can drink alcohol while taking antacids, but alcohol can irritate your stomach and make your symptoms worse.

Antacid side effects

Antacids don’t usually have many side effects if they’re only taken occasionally and at the recommended dose.

But sometimes antacids can cause:

• diarrhea or constipation
• flatulence (wind)
• stomach cramps
• feeling sick or vomiting

These should pass once you stop taking the medicine.

Speak to a pharmacist or your doctor if they don’t improve or are troublesome. You may need to switch to another medicine.

Talk to your provider or pharmacist before taking antacids on a regular basis if:

• You have kidney disease, high blood pressure, or heart disease.
• You are on a low-sodium diet.
• You are already taking calcium.
• You are taking other medicines every day.
• You have had kidney stones.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch/default.htm).

Calcium carbonate with magnesium overdose

The combination of calcium carbonate and magnesium is commonly found in antacids. These medicines provide heartburn relief.

Calcium carbonate with magnesium overdose occurs when someone takes more than the normal or recommended amount of medicine that contains these ingredients. The overdose may be by accident or on purpose.

This is for information only and not for use in the treatment or management of an actual overdose. DO NOT use it to treat or manage an actual overdose. If you or someone you are with overdoses, call your local emergency number, or your local poison center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States.

This national hotline number will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Poisonous Ingredient

Calcium carbonate and magnesium

Where found

Calcium carbonate with magnesium is found in many (but not all) antacids, including the following brands:

• Maalox
• Mylanta
• Rolaids
• Tums

Other antacids may also contain calcium carbonate and magnesium.

Symptoms of calcium carbonate and magnesium overdose

Symptoms of an overdose of calcium carbonate and magnesium include:

• Bone pain (from chronic overuse)
• Constipation
• Decreased reflexes
• Diarrhea
• Dry mouth
• Irregular heartbeat
• Poor balance
• Shallow, rapid breathing
• Skin flushing
• Stupor (lack of alertness)

Home Care

Seek medical help right away. DO NOT make a person throw up unless poison control or a health care provider tells you to.

Before Calling Emergency

Have this information ready:

• Person’s age, weight, and condition
• Name of the product (ingredients and strength, if known)
• Time it was swallowed
• Amount swallowed
• If the medicine was prescribed for the person

What to Expect at the Emergency Room

Take the container with you to the hospital, if possible.

The provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated. The person may receive:

• Activated charcoal
• Blood and urine tests
• Breathing support, including oxygen and a tube through the mouth into the lungs
• Chest (and possibly stomach) x-ray
• ECG (electrocardiogram, or heart tracing)
• Intravenous fluids (given through a vein)
• Laxative
• Medicine to treat symptoms

Outlook (Prognosis)

With proper medical treatment, most people recover completely.

Death can occur from serious heart rhythm disturbances.

References

1. Over-the-Counter Medications in Pregnancy. Am Fam Physician. 2014 Oct 15;90(8):548-555. https://www.aafp.org/afp/2014/1015/p548.html
2. Law R, Maltepe C, Bozzo P, Einarson A. Treatment of heartburn and acid reflux associated with nausea and vomiting during pregnancy. Can Fam Physician. 2010;56(2):143–144.
3. Gill SK, O’Brien L, Koren G. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis. Dig Dis Sci. 2009;54(9):1835–1838.
4. Szumilas M. Explaining Odds Ratios. Journal of the Canadian Academy of Child and Adolescent Psychiatry. 2010;19(3):227-229. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938757/
5. Majithia R, Johnson DA. Are proton pump inhibitors safe during pregnancy and lactation? Evidence to date. Drugs. 2012;72(2):171–179.
6. Gill SK, O’Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol. 2009;104(6):1541–1545.
7. Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010;363(22):2114–2123.
8. Mahadevan U, Kane S. American Gastroenterological Association Institute medical position statement on the use of gastrointestinal medications in pregnancy. Gastroenterology. 2006;131(1):278–282.
9. Einarson A, Mastroiacovo P, Arnon J, et al. Prospective, controlled, multicentre study of loperamide in pregnancy. Can J Gastroenterol. 2000;14(3):185–187.
10. Källén B, Nilsson E, Otterblad Olausson P. Maternal use of loperamide in early pregnancy and delivery outcome. Acta Paediatr. 2008;97(5):541–545.
11. Cullen G, O’Donoghue D. Constipation and pregnancy. Best Pract Res Clin Gastroenterol. 2007;21(5):807–818.
12. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2008.
13. Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK. Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2009;111(3):506–512.
14. Werler MM. Teratogen update: pseudoephedrine. Birth Defects Res A Clin Mol Teratol. 2006;76(6):445–452.
15. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/
16. Physicians’ Desk Reference. http://www.pdr.net
17. Clinical Pharmacology. http://www.clinicalpharmacology.com
18. Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling. https://www.federalregister.gov/documents/2014/12/04/2014-28241/content-and-format-of-labeling-for-human-prescription-drug-and-biological-products-requirements-for

What is bisacodyl

Bisacodyl is a stimulant laxative used to relieve constipation and also to prepare the bowel for diagnostic or surgical procedures requiring the bowel to be empty. Bisacodyl is a diphenylmethane laxative that acts by directly stimulating the nerve endings in the mucosa of the colon, increasing the movement of the intestines. Bisacodyl can help you empty your bowels if you have constipation (difficulty pooing).

Bisacodyl is used in hospitals to help you empty your bowels before surgery or some examinations or treatments. Your hospital will explain how to use it.

Bisacodyl comes as a tablet and a suppository (a medicine that you push gently into your back passage).

Bisacodyl tablets and suppositories are available on prescription and to buy from pharmacies.

Key facts

• Bisacodyl tablets take 6 to 12 hours to work.
• Bisacodyl suppositories take 10 to 45 minutes to work, so it’s best to stay close to a toilet.
• The most common side effects are feeling sick (nausea), diarrhea, stomach pain or cramps.
• Only give bisacodyl to children if their doctor recommends it.
• Do not take bisacodyl tablets or use bisacodyl suppositories every day for more than 5 days.
• Bisacodyl is also called by the brand name Alophen Pills, Bisac-Evac, Carter’s Little Pills, Correctol, Dulcolax, Feen-A-Mint, Fleet Bisacodyl, Bisacodyl Uniserts, Fleet Bisacodyl Enema, Dulcolax Bowel Prep Kit, Bisco-Lax, Doxidan Tablet, Ducodyl, Dulcolax Laxative, Evac-U-Gen, Ex-lax Ultra, Feen-A-Mint, Fleet Bisacodyl, Gen Lax, Magic Bullet, Veracolate, Dulcogen, Bisa-Plex, Bisolax, Gentle Laxative, Laxative Gentle Suppositories, Correct (New Formula), Modane, Colax, Gentlax Tablet and Fematrol.

Who can and can’t take bisacodyl

Bisacodyl can be used by adults.

Bisacodyl can also be used by children, if their doctor recommends it. Doctors normally only recommend it for children aged 4 years and older. Occasionally, they recommend it for children aged 2 years and older.

Bisacodyl enteric-coated tablets are not recommenced for children up to 6 years of age since patients in this age group may have difficulty swallowing the tablet without chewing it ¹. Gastric irritation may develop if the enteric coating is destroyed by chewing ¹.

Furthermore, laxatives should not be given to young children unless prescribed by a physician. Since children are not usually able to describe their symptoms precisely, proper diagnosis should precede the use of laxatives ¹. This will avoid the complication of an existing condition (e.g., appendicitis) or the appearance of more severe side effects ¹.

Bisacodyl isn’t suitable for some people. To make sure it’s safe for you, tell your doctor or pharmacist if you have:

• ever had an allergic reaction to bisacodyl or any other medicines in the past
• signs of dehydration
• severe stomach pain and you are feeling sick or being sick (nausea or vomiting)
• a serious problem in your tummy (abdomen), such as appendicitis, a blockage in your bowel (intestinal obstruction), ulcerative colitis or Crohn’s disease, or a problem with the muscles in your bowel not being able to move food and liquid along

For bisacodyl tablets, also tell your doctor or pharmacist if you:

• can’t digest some sugars – the tablets contain a small amount of lactose and sucrose

For bisacodyl suppositories, also tell your doctor or pharmacist if you have:

• ever had an allergic reaction to suppositories
• tears or open sores (anal fissures) or cracked skin around your back passage (anus)

Before taking bisacodyl – Precautions

• tell your doctor and pharmacist if you are allergic to bisacodyl, any other medications, or any of the ingredients in these products. Check the label or ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• if you are taking antacids, wait at least 1 hour before taking bisacodyl.
• tell your doctor if you have stomach pain, nausea, vomiting, or a sudden change in bowel movements lasting more than 2 weeks.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking bisacodyl, call your doctor.
• talk to your doctor about the risks and benefits of taking this medication if you are 65 years of age or older. Older adults should not usually take bisacodyl because it is not as safe or effective as other medications that can be used to treat the same condition.
• Stimulant laxatives are habit forming and long term use of these drugs may result in laxative dependence and loss of normal bowel function ².

Pediatric use

Safety and effectiveness in pediatric patients has not been established

Geriatric use

Of the 222 patients who received HalfLytely HalfLytely (PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution) and 10 mg bisacodyl tablets bowel prep kit in clinical trials, 73 (33%) were 65 years of age or older, while 18 (8%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between geriatric patients and younger patients but greater sensitivity of some older individuals cannot be ruled out.

Note: HalfLytely is a white powder for reconstitution containing 210 grams of PEG-3350, 2.86 grams of sodium bicarbonate, 5.6 grams of sodium chloride, 0.74 grams of potassium chloride and 1 gram of flavoring ingredient (if applicable). This preparation can be used without the addition of a flavor pack. When dissolved in water to a volume of 2 liters, the HalfLytely solution is isosmotic (having the same osmotic pressure of intracellular fluid), clear, and colorless. The HalfLytely solution is administered orally after taking the two bisacodyl delayed release tablets.

Cautions with other medicines

Some medicines – and some foods – interfere with the way bisacodyl works.

For safety, tell your doctor or pharmacist if you are taking any other medicines, including herbal remedies, vitamins or supplements.

They include:

• water tablets (diuretics), steroids (like prednisolone) or digoxin (a heart medicine) – these can upset the balance of salts and minerals in your body if you have too much bisacodyl by accident. If you are taking digoxin, this imbalance makes it more likely you will have the serious side effects of digoxin. It’s important not to take too much bisacodyl if you are taking any of these medicines.
• indigestion remedies (antacids) and dairy products like milk, cheese and yogurt – these interact with bisacodyl tablets and stop them working properly. They can also make the bisacodyl irritate your stomach and give you indigestion. Do not take bisacodyl at the same time – leave a gap of 1 hour before or after taking bisacodyl if you are having indigestion remedies or dairy products. The small amount of milk in coffee and tea is unlikely to affect it, but it’s best to take bisacodyl tablets with a glass of water.

Mixing bisacodyl with herbal remedies or supplements

There is not enough research to know if complementary medicines and herbal remedies are safe to take with bisacodyl.

Bisacodyl in Pregnancy and Breastfeeding

Tell your pharmacist or doctor if you are trying to get pregnant, already pregnant, or breastfeeding.

FDA Pregnancy Risk Category B: NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility ³.

Bisacodyl tablets or suppositories are not generally recommended if you are pregnant, especially in the first 3 months and while you are breastfeeding. Talk to your doctor about the benefits and risks of taking bisacodyl.

If you are pregnant or breastfeeding, it’s always better to try to treat constipation without taking a medicine. Your doctor or midwife will first advise you to eat more fiber and drink plenty of fluids. It may also help to do gentle exercise.

If diet and lifestyle changes do not work, your doctor or midwife may recommend another laxative, such as lactulose or Fybogel. These are safer laxatives to take during pregnancy and while breastfeeding.

I just found out I am pregnant. Should I stop taking bisacodyl?

Always talk with your healthcare provider before making any changes in your medications. It is important to consider the benefits of treating constipation symptoms during pregnancy.

Constipation may cause pain and other health problems in pregnancy such as cramps, hemorrhoids, and breakdown of the anal tissue. Treating constipation will help reduce the risk of these problems. Dietary changes such as increasing fluids, eating high fiber foods such as whole grains and fresh fruits and vegetables can help prevent constipation. Regular exercise can also help. Although occasional constipation is common in pregnancy, talk with your healthcare provider if constipation becomes an ongoing problem. Your healthcare provider may also want to confirm the diagnosis of constipation and see how dietary and exercise changes can help before discussing medical treatment.

Can the use of laxatives during pregnancy cause birth defects?

Few studies have been done to look at the possible risks from using laxatives during pregnancy. However, the available studies show that when used in recommended doses, laxatives are not expected to increase the risk of birth defects or pregnancy problems.

Are there other concerns when using laxatives?

Yes. Laxatives may reduce the amount of nutrition and medicines that get into the blood since laxatives can make food go through the intestines faster than usual. Nutritional problems are only seen when these agents are used more than recommended.

When more than the recommended amounts of laxatives are used, some can also lower the levels of salts, such as magnesium, in a person’s blood. There is one reported case of low magnesium levels in a newborn that was linked to the mother using too much docusate sodium. The baby’s main symptom was jitteriness, which went away by the second day of life.

Castor oil has been used at the end of pregnancy to bring on labor. It can cause severe diarrhea and cramping of the bowel and uterus. However, if the lower part of the uterus (cervix) is not ready, these contractions will not bring on labor. If you are at the end of your pregnancy, your health care provider can discuss other ways to begin labor.

Bisacodyl and Breastfeeding

Bisacodyl is not absorbed from the gastrointestinal tract, and its active metabolite, which is absorbed, is not detectable in breastmilk ⁴. Bisacodyl can be taken during breastfeeding and no special precautions are required ⁴. Sixteen postpartum women who were not breastfeeding, but were producing at least 200 mL of milk daily by breast pump were given either oral enteric-coated bisacodyl tablets 10 mg daily or oral liquid sodium picosulfate (Laxoberal) 10 mg daily for 7 days ⁵. Both drugs are prodrugs metabolized to the active drug, bis-(p-hydroxyphenyl)-2-pyridyl-2-methane. All breastmilk was collected daily from the day before drug administration to 2 days after the last dose. Free and conjugated bis-(p-hydroxyphenyl)-2-pyridyl-2-methane were undetectable (<1 mcg/L) in all milk samples ⁵.

Bisacodyl contraindications

Bisacodyl tablets bowel prep kit is contraindicated in the following conditions:

• Known allergies to polyethylene glycol or other components of the kit
• Gastrointestinal (GI) obstruction
• Bowel perforation
• Toxic colitis
• Toxic megacolon

Warnings and Precautions

There have been reports of generalized tonic-clonic seizures in patients with use of large volume (4 liter) PEG-based colon preparation products in patients with no prior history of seizures. The seizure cases were associated with severe vomiting, excessive beverage consumption and electrolyte abnormalities (for example, hyponatremia, hypokalemia). The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. Therefore, bisacodyl tablets bowel prep kit should be used with caution in patients using concomitant medications (such as diuretics) that increase the risk of electrolyte abnormalities or patients with known or suspected hyponatremia. Monitor baseline and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients.

Warnings

There have been reports of generalized tonic-clonic seizures in patients with use of large volume (4 liter) PEG-based colon preparation products in patients with no prior history of seizures. The seizure cases were associated with severe vomiting, excessive beverage consumption and electrolyte abnormalities (for example, hyponatremia, hypokalemia). The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. Therefore, bisacodyl tablets bowel prep kit should be used with caution in patients using concomitant medications (such as diuretics) that increase the risk of electrolyte abnormalities or patients with known or suspected hyponatremia. Monitor baseline and post-colonoscopy laboratory tests (sodium, potassium, calcium, creatinine, and BUN) in these patients.

Precautions

Use with caution in patient with severe ulcerative colitis, ileus or gastric retention. Observe patients with impaired gag reflex and patients prone to regurgitation or aspiration during administration of HalfLytely solution. If GI obstruction or perforation is suspected, appropriate studies should be performed to rule out these conditions before administration. There have been reports of ischemic colitis in patients with use of HalfLytely and 20 mg bisacodyl tablets bowel prep kit. If patients develop severe abdominal pain or rectal bleeding, patients should be evaluated as soon as possible.

Patients with impaired water handling who experience severe vomiting should be closely monitored including measurement of electrolytes (sodium, potassium, calcium, BUN and creatinine). Hives and skin rashes have been reported with PEG-3350 based products which are suggestive of an allergic reaction.

How does bisacodyl work

Bisacodyl is in a class of medications called stimulant laxatives. It works by increasing activity of the intestines to cause a bowel movement.

Bisacodyl is hydrolyzed by intestinal brush border enzymes and colonic bacteria to form an active metabolite [bis-(p-hydroxyphenyl) pyridyl-2 methane; (BHPM)] that acts directly on the colonic mucosa to produce colonic peristalsis.

Bisacodyl is used on a short-term basis to treat constipation. It also is used to empty the bowels before surgery and certain medical procedures.

Bisacodyl has been used to facilitate flushing of colostomies and may reduce or eliminate the need for irrigations.

What is bisacodyl used for

Bisacodyl is used for treatment of occasional constipation, or to prepare patients for radiological examinations of the colon, sigmoidoscopy, and proctologic examinations, and for pre-operative bowel preparation.

Bisacodyl is used:

• to treat constipation that occurs following prolonged bed rest or hospitalization.
• to treat chronic constipation associated with opiate therapy.
• to treat constipation occurring secondary to idiopathic slowing of transit time, to constipating drugs, or to irritable bowel or spastic colon syndrome.
• to treat constipation in patients with neurologic constipation.

How should bisacodyl be used?

Bisacodyl comes as a tablet to take by mouth. Swallow the tablets whole with a glass of water; do not split, chew, or crush them. Do not take bisacodyl within 1 hour after drinking or eating dairy products. Bisacodyl is usually taken the evening before a bowel movement is desired. Do not take bisacodyl more than once a day or for more than 1 week without talking to your doctor. Follow the directions on the package or on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take bisacodyl exactly as directed. Frequent or continued use of bisacodyl may make you dependent on laxatives and cause your bowels to lose their normal activity.

What special dietary instructions should I follow?

A regular diet and exercise program is important for regular bowel function. Eat a high-fiber diet and drink plenty of liquids (eight glasses) each day as recommended by your doctor.

How long does it take for bisacodyl to work?

Bisacodyl tablet taken by mouth normally causes a bowel movement within 6 to 12 hours. If you do not have a regular bowel movement after taking bisacodyl, do not take any more medication and talk to your doctor.

Bisacodyl suppositories take 10 to 45 minutes to work, so it’s best to stay close to a toilet.

How long should I take bisacodyl for?

Do not take bisacodyl every day for more than 5 days. If you are still constipated after that, talk to your doctor.

Is it safe to take bisacodyl for a long time?

Ideally, you should only use bisacodyl occasionally and for a few days at a time.

Using laxatives like bisacodyl for longer can lead to a fluid and salt imbalance in your body and you may become dehydrated.

If you need to use laxatives every day for a longer time, talk to your doctor.

With long term use or overdosage of stimulant laxatives, electrolyte disturbances including hypokalemia, hypocalcemia, metabolic acidosis or alkalosis, abdominal pain, diarrhea, malabsorption, weight loss, and protein-losing enteropathy may occur ². Electrolyte disturbances may produce vomiting and muscle weakness; rarely osteomalacia, secondary aldosteronism, and tetany may occur. Pathologic changes in including structural damage to the myenteric plexus, severe and permanent interference with colonic motility, and hypertrophy of the muscularis mucosae may occur with chronic use ².

Can I take different laxatives together?

For most people, 1 laxative will be enough to make your constipation better.

Occasionally, you may need to take 2 different types of laxatives at the same time to get your bowels moving again. Only take 2 laxatives together if your doctor or pharmacist tell you to as this increases the risk of side effects.

Are other laxatives any better?

There are other types of laxative. They work in a different way from bisacodyl, but are equally good at treating constipation.

• Bulk-forming laxatives, for example Fybogel and methylcellulose. These increase the “bulk” or weight of poo, which in turn stimulates bowel movement. They take 2 or 3 days to work.
• Osmotic laxatives, for example lactulose. These draw water from the rest of the body into your bowel to soften your poo and make it easier to pass. They take at least 2 days to work.
• Stimulant laxatives, for example senna. These stimulate the muscles that line your gut, helping them to move poo along your gut to your back passage. Senna takes about 8 hours to work.

Can I use bisacodyl after surgery?

It’s quite common to have constipation after surgery. Using a laxative may help.

If you have constipation after an operation, it’s better to use lactulose because it is gentler than bisacodyl. You can get it on prescription or buy it from pharmacies.

Can lifestyle changes help constipation?

It’s often possible to improve constipation without having to use laxatives. Before trying bisacodyl – or to stop constipation coming back – it may help to:

• eat more fiber – aim for about 30-35 g of fiber a day. High-fiber foods include fruit, vegetables and cereals. If you’re not used to a high-fiber diet, increase the amount of fiber you eat gradually.
• add bulking agents, such as wheat bran, to your diet. These will help make your poo softer and easier to pass (although bran and fiber can sometimes make bloating worse).
• drink plenty of water – to keep poo soft.
• exercise regularly – keeping your body active will help to keep your gut moving.
• go to the toilet when you need to, rather than holding it in.

Bisacodyl dosage

Alleviation of constipation can be expected within 8 to 12 hours if taken at bedtime or within 6 hours if taken during waking hours. You may find that it is most convenient to take bisacodyl about 30 to 60 minutes before your normal bedtime in order to produce a bowel movement in the morning.

Usual Adult Dose for Bowel Preparation

• 5 to 15 mg (1 to 3 tablets) orally once a day as needed or
• 10 mg (1 suppository) rectally once a day as needed or
• 10 mg rectal liquid once a day as needed.

Usual Adult Dose for Constipation

• 5 to 15 mg (1 to 3 tablets) orally once a day as needed or
• 10 mg (1 suppository) rectally once a day as needed or
• 10 mg rectal liquid once a day as needed.

Renal Dose Adjustments

• No adjustment recommended.
• Caution is recommended when using bisacodyl enemas containing monobasic or dibasic sodium phosphate in patients with impaired renal function or where colostomy exists as hypocalcemia, hyperphosphatemia, hypernatremia, and acidosis may occur.

Liver Dose Adjustments

No adjustment recommended

Dialysis

No adjustment recommended

How and when to take bisacodyl

Before using rectal bisacodyl

• tell your doctor and pharmacist if you are allergic to bisacodyl, any other medications, or any of the ingredients in these products. Check the label or ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have stomach pain, nausea, vomiting, a sudden change in bowel movements lasting more than 2 weeks, anal fissures, or hemorrhoids.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using rectal bisacodyl, call your doctor.
• talk to your doctor about the risks and benefits of using this medication if you are 65 years of age or older. Older adults should not usually use rectal bisacodyl because it is not as safe or effective as other medications that can be used to treat the same condition.

How to take bisacodyl

Bisacodyl Tablets

• Take the medicine once a day just before bedtime.
• You can take it with or without food. Swallow the tablet whole with water.
• Do not have milk, indigestion remedies (antacids) or medicines to reduce stomach acid (for example, proton pump inhibitors) at the same time as bisacodyl. This is because they will stop the medicine working properly. Leave a gap of 1 hour between taking any of these and taking your bisacodyl tablets.

Bisacodyl Suppositories

• Take the wrapping off and push a suppository gently into your back passage (anus).
• Suppositories work quickly (usually between 10 and 45 minutes), so use it when you know you will be near a toilet.
• Read the instructions in the leaflet inside the package. They will explain how to use the suppository.

Rectal bisacodyl comes as a suppository and enema to use rectally. It is usually used at the time that a bowel movement is desired. The suppositories usually cause a bowel movement within 15 to 60 minutes and the enema within 5 to 20 minutes. Do not use bisacodyl more than once a day or for more than 1 week without talking to your doctor. Follow the directions on the package or on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use rectal bisacodyl exactly as directed. Frequent or continued use of bisacodyl may make you dependent on laxatives and cause your bowels to lose their normal activity. If you do not have a regular bowel movement after using bisacodyl, do not use this medication again and talk to your doctor.

If using a bisacodyl suppository, follow these steps:

1. If the suppository is soft, hold it under cool water or place it in the refrigerator for a few minutes to harden it before removing the wrapper.
2. Remove the wrapper.
3. If you were told to use half of the suppository, cut it lengthwise with a clean, sharp knife or blade.
4. Lie down on your left side and raise your right knee to your chest.
5. Using your finger, insert the suppository, pointed end first, into your rectum until it passes the muscular sphincter of the rectum, about 1 inch (2.5 centimeters) in adults. If not inserted past this sphincter, the suppository may pop out.
6. Hold it in place for as long as possible.
7. Wash your hands thoroughly.

If using a bisacodyl enema, follow these steps:

1. Shake the enema bottle well.
2. Remove the protective shield from the tip.
3. Lie down on your left side and raise your right knee to your chest or kneel and lean forward so that your head and chest are resting comfortably.
4. Gently insert the enema bottle into the rectum with the tip pointing toward the navel.
5. Squeeze the bottle gently until the bottle is nearly empty.
6. Remove the enema bottle from the rectum. Hold the enema contents in place as long as possible, for up to 10 minutes.
7. Wash your hands thoroughly.

How much bisacodyl to take

Bisacodyl Tablets

The usual dose in:

• adults and children aged 12 years and over is 5—15 mg/day (1 to 3 tablets) once a day before bedtime
• children aged 6 to 11 years old is 5 mg (1 tablet) a day before bedtime, if their doctor recommends it

If you are an adult or child aged 10 and over and you have not taken bisacodyl before, start with 1 tablet. If that doesn’t work well enough for you, you can take 2 tablets.

Bisacodyl Suppositories

The usual dose for:

• adults and children aged 12 years and over is 1 suppository (10mg) a day
• children 6 to 12 years old is 1 suppository (5mg) a day, if their doctor recommends it

What if I forget to take it?

If you forget a dose of bisacodyl, don’t worry. Just take the next dose at the usual time.

Never take 2 doses at the same time. Never take an extra dose to make up for a forgotten one.

What if I take too much?

Taking an extra dose of bisacodyl by accident is unlikely to harm you. You may get diarrhea and stomach pain, but this should get better within a day or two.

If you’re worried, talk to your doctor or pharmacist for advice.

Is there any food and drink I need to avoid?

Do not take bisacodyl at the same time as dairy products like milk, cheese or yogurt. Leave a gap of 1 hour between taking any of these and taking your bisacodyl tablets. The small amount of milk in coffee and tea should not affect the bisacodyl tablet.

It’s a good idea to stop eating pastries, cakes, puddings and cheese for a while as these can make constipation worse.

Can I drink alcohol with bisacodyl?

Yes, you can drink alcohol with bisacodyl.

Bisacodyl side effects

Like all medicines, bisacodyl may cause side effects in some people, but many people have no side effects or only minor ones.

Common side effects

Common side effects, which happen in more than 1 in 100 people, are:

• feeling sick (nausea)
• diarrhea
• stomach pain or cramps
• stomach cramps
• faintness
• rectal administration of bisacodyl suspensions or suppositories may cause irritation and a sensation of burning of the rectal mucosa and mild proctitis (for rectal bisacodyl)

These side effects are mild and usually go away after a couple of days. Talk to your doctor or pharmacist if the side effects bother you or don’t go away.

Gastrointestinal

Bisacodyl causes acute nonspecific inflammatory injury to the rectal mucosa, which can confound the assessment of patients with suspected inflammatory bowel disease.

The surreptitious abuse of laxatives is a common cause of severe chronic diarrhea. In some cases, the stool contains fecal leukocytes, which, in this case, is indicative of the irritant effect of bisacodyl (nonspecific colonic mucosal inflammation), and not necessarily of infection. Surreptitious abuse of laxatives due to bisacodyl can be determined by urinalysis for a metabolite, bisacodyl diphenol. In some cases, stool analysis for bisacodyl could be considered in the diagnostic assessment.

Abdominal cramping has been described as a mild, colicky discomfort. This can be a problem since cramping my indicate not only a side effect of bisacodyl, but underlying gastrointestinal pathology.

Abdominal distension and vomiting are less common gastrointestinal side effects.

Gastrointestinal side effects have been reported the most frequently. These have included abdominal cramping, diarrhea, abdominal distention, and vomiting. Severe diarrhea has been reported as a possible result of surreptitious laxative abuse. The sensation of rectal “burning” with administration of bisacodyl enema has been reported.

Metabolic

The metabolic consequences of some Fleet bisacodyl enema preparation kits that contain monobasic or dibasic sodium phosphate in patients with renal insufficiency can be profound. Due to the sodium and phosphate absorption, severe hypernatremia, hypophosphatemia, and hypocalcemia may occur.

Metabolic side effects have included severe hypernatremia, hypophosphatemia, and hypocalcemia. These effects have been reported primarily with Fleet bisacodyl enema preparation kits that contain monobasic or dibasic sodium phosphate and administered to patients with renal insufficiency. Fleet bisacodyl enemas without these ingredients may be used safely in such patients.

Serious side effects

Call your doctor straight away if these rare side effects happen to you:

• feeling dizzy
• blood in your poo
• rectal bleeding
• being sick (vomiting)

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction to bisacodyl.

• A serious allergic reaction is an emergency. Contact a doctor straight away if you think you or someone around you is having a serious allergic reaction.

The warning signs of a serious allergic reaction are:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• wheezing
• tightness in the chest or throat
• having trouble breathing or talking
• swelling of the mouth, face, lips, tongue or throat

These are not all the side effects of bisacodyl. For a full list, see the leaflet inside your medicines packet.

How to cope with side effects

What to do about:

• feeling sick – try taking bisacodyl with some food.
• diarrhea – stop taking bisacodyl and drink plenty of water or other fluids. Speak to a pharmacist if you have signs of dehydration, such as
• peeing less than usual or having dark, strong-smelling pee. Don’t take any other medicines to treat diarrhea without speaking to a pharmacist or doctor.
• stomach pain or cramps – reduce your dose of bisacodyl or stop taking it until these side effects go away.

Human Toxicity Reports

Mild to moderate toxicity

• Nausea, vomiting, abdominal pain, and diarrhea have been reported.

Severe toxicity

• Fluid and electrolyte depletion, hypotension from extensive fluid losses, blisters, and skin sloughing of the buttocks and perineum with diarrhea.

Chronic toxicity

• Electrolyte abnormalities (e.g., hypochloremia, hypokalemia, hypocalcemia, hypomagnesemia), reflex bowel hypofunction, permanent colonic dysfunction (cathartic colon, causing chronic constipation, bloating, and abdominal pain), frank/occult gastrointestinal bleeding and associated anemia, steatorrhea, protein-loss gastroenteropathy, pancreatic dysfunction. Toxic hepatitis and jaundice have been reported following the chronic use of very large doses of senna.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in clinical studies of another drug and may not reflect the rates observed in practice. In a clinical study of HalfLytely and (10 mg vs. 20 mg) bisacodyl tablets bowel prep kit multicentered, controlled clinical trials, abdominal pain/cramping, nausea, vomiting and headache were the most common adverse reactions ( 3%) after the administration of HalfLytely and (10 mg or 20 mg) bisacodyl tablets bowel prep kit. Less than 1% of patients exposed to HalfLytely and 10 mg bisacodyl tablets bowel prep kit reported vomiting and abdominal pain/cramping. The data in reflects exposure in 222 patients to HalfLytely and 10 mg bisacodyl tablets vs. 223 patients exposed to HalfLytely and 20 mg bisacodyl tablets. The HalfLytely and 10 mg bisacodyl tablets bowel prep kit population was 20-85 years of age, 46% male, 54% female, 10% African American, 85% Caucasian, 8% Hispanic requiring a colonoscopy. The demographics of the comparator group were similar.

In therapeutic oral doses, all stimulant laxatives may produce some degree of abdominal discomfort, nausea, mild cramps, griping, and/or faintness. Rectal administration of bisacodyl suspensions may cause irritation and a sensation of burning of the rectal mucosa and mild proctitis ².

Weakness, incoordination, and orthostatic hypotension may be exacerbated in elderly patients as a result of significant electrolyte loss when stimulant laxatives are used repeatedly to evacuate the colon ¹.

Suppository may produce mild feeling of a sharp stinging pain or tenesmus, and with continued rectal administration may cause proctitis ⁶. Sloughing of surface of epithelium of rectum has been observed. Inflammatory changes that occur after short-term use of bisacodyl suppositories may resemble those seen in mild idiopathic ulcerative proctitis.

Bisacodyl should not be given to patients with intestinal obstruction or acute abdominal conditions such as appendicitis; care should be taken in patients with inflammatory bowel disease. It should not be used in patients with severe dehydration. The suppositories should preferably be avoided in patients with anal fissures, proctitis, or ulcerated hemorrhoids ⁷.

A case report on a female patient with frequent, repetitive formation of kidney stones and rapid double J stent encrustation, which were related to the chronic abuse of bisacodyl. Although these stones can be fragmented successfully by extracorporeal shockwave lithotripsy, it seems that the better treatment for this type of stone formation is to avoid the abuse of laxatives ⁸.

A case report a case of ammonium acid urate stone due to laxative abuse ⁹. A 27-year-old female complained of left flank pain. Computed tomography revealed bilateral ureter stones (right 16.5 x 9.0 mm; left 4 mm), while left ureter stone was radiolucent on the plain X ray film. Bilateral hydronephrosis was seen, but no therapy was performed for the right stone, because 99mTc-MAG3 scintigraphy revealed that right kidney had no function. The left stone was successfully removed by transurethral approach. The stone was revealed to be an ammonium acid urate by infrared spectrophotometry. She had been taking many laxatives (bisacodyl, sennoside, aloe extract) for 12 years to control her body weight ⁹. Ammonium acid urate stones are rarely seen in developed countries. We have reviewed 9 cases in Japan, describing ammonium acid urate stones due to laxative abuse. Among these patients, 24-hour urine volume and excretion in urinary sodium were decreased, and serum aldosterone was increased. The involvement of laxative abuse should be considered when ammonium acid urate is formed in a woman with a low body mass index ⁹.

References

1. Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 1732
2. McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 2784
3. Cowl, C.T. Physician’s Handbook 10th edition. Lippincott Williams & Wilkins, Philadelphia, PA. 2003, p. 209
4. Bisacodyl https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~38hWnu:5
5. Friedrich C, Richter E, Trommeshauser D et al. Lack of excretion of the active moiety of bisacodyl and sodium picosulfate into human breast milk: an open-label, parallel group, multiple dose study in healthy lactating women. Drug Metab Pharmacokinet. 2011;26:458-64 https://www.jstage.jst.go.jp/article/dmpk/26/5/26_DMPK-11-RG-007/_pdf/-char/en
6. American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 813
7. Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1363
8. Wu WJ et al; J Formos Med Assoc 92 (11): 1004-6; 1993 https://www.ncbi.nlm.nih.gov/pubmed/7910057
9. Kato Y et al; Hinyokika Kiyo 50 (11): 799-803; 2004 https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/113488/1/50_799.pdf

What is paracetamol

Paracetamol also known as acetaminophen, is a pain reliever and a fever reducer medicine. Paracetamol (acetaminophen) is a commonly used medicine to relieve mild or moderate pain, such as muscle aches, arthritis, backaches, menstrual periods, toothaches, colds, sore throats or sprains, reactions to vaccinations (shots) and reduce a high temperature (fever) caused by illnesses such as colds and flu.

Paracetamol may also be used to relieve the pain of osteoarthritis (arthritis caused by the breakdown of the lining of the joints). Paracetamol is in a class of medications called analgesics (pain relievers) and antipyretics (fever reducers). Paracetamol works by changing the way the body senses pain and by cooling the body.

Paracetamol is often recommended as one of the first treatments for pain, as it’s safe for most people to take and side effects are rare. Paracetamol is a common active ingredient to treat pain and reduce fever; it is included in many prescription and over-the-counter (OTC) products.

Paracetamol has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.

Paracetamol is a widely used nonprescription analgesic and antipyretic medication for mild-to-moderate pain and fever. Harmless at low doses, paracetamol has direct hepatotoxic potential when taken as an overdose and can cause acute liver injury and death from acute liver failure. Even in therapeutic doses, paracetamol can cause transient serum aminotransferase elevations (liver enzymes).

Paracetamol can cause unusual results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using paracetamol.

You can take paracetamol for:

• mild to moderate pain, for example backache, headache, migraine, muscle strains, period pain, toothache and aches and pains due to colds and flu
• fever (high temperature)
• osteoarthritis and other painful, non-inflammatory conditions.

An overdose of paracetamol can damage your liver or cause death.

• Adults and teenagers who weigh at least 110 pounds should not take more than 1000 milligrams (mg) at one time, or more than 4000 mg in 24 hours.
• Children younger than 12 years old should not take more than 5 doses in 24 hours, using only the number of milligrams per dose that is recommended for the child’s weight and age. Use exactly as directed on the label.

Avoid also using other medicines that contain paracetamol (sometimes abbreviated as APAP), or you could have a fatal overdose.

• You should not use paracetamol if you have severe liver disease.

Is it okay to drink alcohol when I’m taking paracetamol?

Drinking a small amount of alcohol is unlikely to be harmful if you are taking paracetamol.

Paracetamol and pregnancy

Paracetamol is considered the first choice of painkiller if you are pregnant since it has been taken by large numbers of pregnant women without any adverse effect on the mother or baby.

However, if you take paracetamol when pregnant, make sure you take it for the shortest possible time.

Can I take paracetamol if I’m breastfeeding?

Paracetamol is the first choice of painkiller if you are breastfeeding.

It appears in breast milk in very small amounts which are unlikely to harm your baby.

If you take paracetamol when breastfeeding, make sure you take it for the shortest possible time.

How does paracetamol work?

Paracetamol is a p-aminophenol derivative, an odorless compound with a slightly bitter taste with analgesic and antipyretic activities that seems to work by blocking chemical messengers in the brain that tell you that you have pain. Although the exact mechanism through which acetaminophen exert its effects has yet to be fully determined, acetaminophen may inhibit the nitric oxide (NO) pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate (NMDA) and substance P, resulting in elevation of the pain threshold. The antipyretic activity may result from inhibition of prostaglandin synthesis and release in the central nervous system (CNS) and prostaglandin-mediated effects on the heat-regulating body temperature center in the anterior hypothalamus.

Paracetamol is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS) ¹. The effects of paracetamol (acetaminophen) on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol was investigated. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 a, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2 a was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. It was concluded that paracetamol (acetaminophen) does not increase oxidative stress in humans ¹.

Is paracetamol ibuprofen?

No. Ibuprofen belongs to one of a group of painkillers called non-steroidal anti-inflammatory drugs (NSAIDs). Ibuprofen is better for reducing inflammation (redness and swelling), including teething and toothache.

Whereas paracetamol is usually best for most types of pain, including headache and stomach ache.

Paracetamol and ibuprofen are similar strengths, but they work in different ways. So paracetamol is better for some types of pain than ibuprofen.

Do not give ibuprofen and paracetamol together, though. Instead, if you’ve given paracetamol to your child and they’re still feverish or in pain when the next dose is due, you could try ibuprofen instead.

Don’t take more than the maximum daily dose of either medicine. See your doctor if you’ve tried both ibuprofen and paracetamol and they haven’t helped.

Who can take paracetamol

Most people can take paracetamol safely, including:

• pregnant women
• breastfeeding women
• children over 2 months of age – lower doses are recommended for young children

If you’re not sure whether you can take paracetamol, check the leaflet that comes with it or ask your pharmacist or doctor for advice.

Always get advice before taking paracetamol if you:

• have liver or kidney problems
• have problems with alcohol, such as long-term alcohol misuse
• are very underweight
• are taking other medications

Don’t take paracetamol if you’ve had an allergic reaction to acetaminophen (paracetamol) in the past.

Before taking paracetamol

• tell your doctor and pharmacist if you are allergic to paracetamol, any other medications, or any of the ingredients in the product. Ask your pharmacist or check the label on the package for a list of ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, or herbal products you are taking or plan to take. Be sure to mention anticoagulants (‘blood thinners’) such as warfarin (Coumadin); isoniazid (INH); certain medications for seizures including carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin); medications for pain, fever, coughs, and colds; and phenothiazines (medications for mental illness and nausea). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have ever developed a rash after taking paracetamol.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking paracetamol, call your doctor.
  if you drink three or more alcoholic beverages every day, do not take paracetamol. Ask your doctor or pharmacist about the safe use of alcoholic beverages while taking paracetamol.
• you should know that combination paracetamol products for cough and colds that contain nasal decongestants, antihistamines, cough suppressants, and expectorants should not be used in children younger than 2 years of age. Use of these medications in young children can cause serious and life-threatening effects or death. In children 2 through 11 years of age, combination cough and cold products should be used carefully and only according to the directions on the label.
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of acetaminophen chewable tablets may be sweetened with aspartame. a source of phenylalanine.

Figure 1. Paracetamol structure

 

Paracetamol vs acetaminophen

Paracetamol is acetaminophen.

Who can and can’t take paracetamol

Children can take paracetamol as:

• a liquid syrup – from the age of 3 months (2 months if they have a fever after a vaccination)
• suppository – from the age of 3 months (2 months if they have a fever after a vaccination)
• tablets – from the age of 6 years (500mg so they may need to be broken)
• soluble tablets – from the age of 12 years

Check with your doctor or pharmacist if your child:

• is small for their age as a lower dose may be better
• has had liver or kidney problems
• takes medicine for epilepsy
• takes medicine for tuberculosis (TB)

Giving paracetamol with other painkillers

The only safe painkiller to give children alongside paracetamol is ibuprofen.

• Do not give paracetamol and ibuprofen together, though. Instead, if you’ve given them paracetamol and they’re still feverish or in pain when the next dose is due, you could try ibuprofen instead.
• Don’t take more than the maximum daily dose of either medicine. See your doctor if you’ve tried both paracetamol and ibuprofen and they haven’t helped. Do not give ibuprofen to your child if they have asthma, unless your doctor has said it’s okay.
• Don’t give your child another medicine with paracetamol in it. If they take 2 different medicines that contain paracetamol, there’s a risk of overdose. Paracetamol is an ingredient in lots of medicines that you can buy from the supermarket or pharmacy.
• Never give aspirin to a child under the age of 16 (unless prescribed by a doctor).

Never give aspirin to a child under the age of 16 (unless prescribed by a doctor).

Paracetamol for Children Uses

Temporarily:

• reduces fever
• relieves minor aches and pains due to:
• the common cold
• flu
• headache
• sore throat
• toothache

Paracetamol for Children Warnings

Liver warning

This product contains acetaminophen. Severe liver damage may occur if your child takes:

• more than 5 doses in 24 hours, which is the maximum daily amount
• with other drugs containing paracetamol

Allergy alert

Paracetamol may cause severe skin reactions. Symptoms may include:

• skin reddening
• blisters
• rash

If a skin reaction occurs, stop use and seek medical help right away.

Sore throat warning

• If sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, nausea, or vomiting, consult a doctor promptly.

Do NOT use

• with any other drug containing paracetamol (prescription or nonprescription). If you are not sure whether a drug contains paracetamol, ask a doctor or pharmacist.
• if your child is allergic to paracetamol or any of the inactive ingredients in this product

Ask a doctor before use if your child has liver disease

Ask a doctor or pharmacist before use if your child is taking the blood thinning drug warfarin. Long-term use of paracetamol may increase the effect of warfarin, which can increase the risk of bleeding. However, this is unlikely to happen with the occasional use of paracetamol.

When using paracetamol, do not exceed recommended dose.

Stop use and ask a doctor if:

• pain gets worse or lasts more than 5 days
• fever gets worse or lasts more than 3 days
• new symptoms occur
• redness or swelling is present

These could be signs of a serious condition.

Keep out of reach of children.

Overdose warning: In case of overdose, get medical help or contact a Poison Control Center right away.

Is there any food or drink they need to avoid?

Your child can eat and drink normally while taking paracetamol.

You can give your child paracetamol on an empty stomach.

What if my child vomits?

• If your child vomits less than 30 minutes after having a dose of paracetamol tablets or syrup, give them the same dose again.
• If your child vomits more than 30 minutes after a dose of tablets or syrup, you do NOT need to give them another dose. Wait until the next normal dose.

If your child is finding it hard to keep tablets or syrup down, ask your doctor if acetaminophen (paracetamol) suppositories are an option. If they vomit straight after a suppository, you don’t need to give them another dose as the suppository will still work.

What if they take too much?

Giving your child too much paracetamol by accident can be dangerous. The effects of an overdose may not be obvious, but they can be serious and need treatment.

If you think you may have given your child an extra dose of paracetamol by mistake, wait at least 24 hours before giving them any more.

If you think you may have given your child more than the recommended total daily dose of paracetamol, seek advice immediately, even if your child feels well. Go to your nearest hospital emergency department and seek urgent medical attention.

If you need to take your child to hospital, take the paracetamol packet or leaflet inside it plus any remaining medicine with them.

Paracetamol for adults

Paracetamol is a common painkiller used to treat aches and pain. It can also be used to reduce fever 100.4 °F (38 °C) or above.

It’s also available combined with other painkillers and anti-sickness medicines. It’s an ingredient in a wide range of cold and flu remedies.

Key facts

• Paracetamol takes up to an hour to work.
• The usual dose of paracetamol is one or two 500mg tablets at a time.
• Don’t take paracetamol with other medicines containing paracetamol.
• Paracetamol is safe to take in pregnancy and while breastfeeding, at recommended doses.
• Paracetamol is widely available as tablets and capsules. For people who find it difficult to swallow tablets or capsules, paracetamol is also available as soluble tablets that dissolve in water to make a drink and as a syrup.

Who can and can’t take paracetamol

Most people can take paracetamol safely, including pregnant and breastfeeding women.

However, some people need to take extra care with paracetamol.

Check with your doctor or pharmacist if you:

• have had an allergic reaction to acetaminophen (paracetamol) or any other medicines in the past
• have liver or kidney problems
• regularly drink more than the maximum recommended amount of alcohol (14 units a week)
• take medicine for epilepsy
• take medicine for tuberculosis (TB)
• take the blood-thinner warfarin and you may need to take paracetamol on a regular basis.

Paracetamol for Adults Uses

• Temporarily relieves minor aches and pains due to:
  • the common cold
  • headache
  • backache
  • minor pain of arthritis
  • toothache
  • muscular aches
  • premenstrual and menstrual cramps
• Temporarily reduces fever

Paracetamol for Adults Warnings

Liver warning

This product contains paracetamol. Severe liver damage may occur if you take

• more than 4,000 mg of paracetamol in 24 hours
• with other drugs containing paracetamol
• 3 or more alcoholic drinks every day while using this product

Allergy alert

Paracetamol may cause severe skin reactions. Symptoms may include:

• skin reddening
• blisters
• rash

If a skin reaction occurs, stop use and seek medical help right away.

Do NOT use

• with any other drug containing paracetamol (prescription or nonprescription). If you are not sure whether a drug contains paracetamol, ask a doctor or pharmacist.
• if you are allergic to paracetamol or any of the inactive ingredients in this product

Ask a doctor before use if you have liver disease

Ask a doctor or pharmacist before use if you are taking the blood thinning drug warfarin. Long-term use of paracetamol may increase the effect of warfarin, which can increase the risk of bleeding. However, this is unlikely to happen with the occasional use of paracetamol.

Stop use and ask a doctor if:

• pain gets worse or lasts more than 10 days
• fever gets worse or lasts more than 3 days
• new symptoms occur
• redness or swelling is present

These could be signs of a serious condition.

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children.

Overdose warning: In case of overdose, get medical help or contact a Poison Control Center right away.

How many paracetamol can I take?

The usual dose for adults is one or two 500mg paracetamol tablets up to 4 times in 24 hours.

Always leave at least 4 hours between doses.

Overdosing on paracetamol can cause serious side effects. Don’t be tempted to increase the dose or take a double dose if your pain is very bad.

• The total maximum dose of paracetamol for an adult is eight 500mg tablets in 24 hours. Wait at least 4 hours between doses.

Adult dose (over-16s only)

• Total maximum dose of paracetamol for an adult is eight 500mg tablets in 24 hours
  • take one to two 500mg caplets while symptoms last, wait 4-6 hours
  • take one to two 500mg caplets while symptoms last, wait 4-6 hours
  • take one to two 500mg caplets while symptoms last, wait 4-6 hours
  • take one to two 500mg caplets while symptoms last, wait 4-6 hours
• do NOT take more than 6 caplets in 24 hours, unless directed by a doctor
• do NOT take for more than 10 days unless directed by a doctor

Paracetamol max dose (over-16s only)

• 8 x 500 mg = 4,000 mg in 24 hours

What if I take too much?

Taking one or 2 extra tablets by accident is unlikely to be harmful. Wait at least 24 hours before you take any more paracetamol.

Taking more than 2 extra paracetamol tablets can be dangerous and may need treatment.

If you have taken more than the recommended total daily dose of paracetamol, seek advice immediately, even if you feel well. Go to your nearest hospital emergency department and seek urgent medical attention.

If you need to go to hospital, take the paracetamol packet or leaflet inside it plus any remaining medicine with you.

What if I forget to take it?

If you take paracetamol regularly and miss a dose, take it as soon as you remember. If it’s close to the time for your next dose when you remember, then skip the missed dose.

Never take double doses of paracetamol. Never take extra doses to catch up.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

Taking paracetamol with other painkillers

It’s safe to take paracetamol with other types of painkiller that don’t contain paracetamol, such as ibuprofen, aspirin and codeine.

Don’t take paracetamol alongside other medicines that contain paracetamol. If you take 2 different medicines that contain paracetamol, there’s a risk of overdose.

Pharmacy remedies that contain paracetamol include some:

• migraine remedies
• cough and cold products

Paracetamol may also be combined with other painkillers in medicines that have been prescribed by your doctor, such as:

• co-codamol (paracetamol and codeine)
• co-dydramol (paracetamol and dihydrocodeine)
• tramacet (paracetamol and tramadol)

Paracetamol uses

Paracetamol is used to relieve mild to moderate pain from headaches, muscle aches, menstrual periods, colds and sore throats, toothaches, backaches, and reactions to vaccinations (shots), and to reduce fever. paracetamol may also be used to relieve the pain of osteoarthritis (arthritis caused by the breakdown of the lining of the joints). paracetamol is in a class of medications called analgesics (pain relievers) and antipyretics (fever reducers). Paracetamol works by changing the way the body senses pain and by cooling the body.

 

Paracetamol dosage

Applies to the following strengths paracetamol: 160 mg; 80 mg/0.8 mL; 160 mg/5 mL; 500 mg; 650 mg; 80 mg; 325 mg; 500 mg/15 mL; 120 mg; 120 mg/5 mL; 80 mg/5 mL; 10 mg/mL; 650 mg/25 mL; 80 mg/mL; 500 mg/5 mL; 48 mg/mL.

Measure liquid paracetamol with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Paracetamol made for infants is available in two different dose concentrations, and each concentration comes with its own medicine dropper or oral syringe. These dosing devices are not equal between the different concentrations. Using the wrong device may cause you to give your child an overdose of paracetamol. Never mix and match dosing devices between infant formulations of paracetamol.

You may need to shake the liquid before each use. Follow the directions on the medicine label.

The chewable tablet must be chewed thoroughly before you swallow it.

Make sure your hands are dry when handling the paracetamol disintegrating tablet. Place the tablet on your tongue. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

To use the paracetamol effervescent granules, dissolve one packet of the granules in at least 4 ounces of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Usual Adult Dose for Fever

Doses may be given as a single or repeated dose as follows:

Oral:

Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours

Extended-Release: 1300 mg orally every 8 hours
Maximum dose: 3900 mg per 24 hours

Rectal:

650 mg rectally every 4 to 6 hours
Maximum dose: 3900 mg per 24 hours

Parenteral:

Weight 50 kg or greater: 1000 mg IV every 6 hours OR 650 mg IV every 4 hours

Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 4000 mg per 24 hours

Weight less than 50 kg: 15 mg/kg IV every 6 hours OR 12.5 mg/kg IV every 4 hours

Maximum Single Dose: 15 mg/kg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 75 mg/kg per 24 hours

Comments:

• Maximum daily dose is based on all routes of administration and all products containing paracetamol.
• Maximum daily dose and dosing recommendations may differ by product; some manufacturers have decreased the maximum daily dose to protect consumers from inadvertent overdoses.
• For IV administration, verify the dose in mg and mL to ensure the dose is correct; verify that infusion pumps are properly programmed

Uses:

• For the management of mild to moderate pain and the management of moderate to severe pain with adjunctive opioid analgesics.
• For the reduction of fever.

Usual Adult Dose for Pain

Doses may be given as a single or repeated dose as follows:

Oral:

Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours

Extended-Release: 1300 mg orally every 8 hours
Maximum dose: 3900 mg per 24 hours

Rectal:

650 mg rectally every 4 to 6 hours
Maximum dose: 3900 mg per 24 hours

Parenteral:

Weight 50 kg or greater: 1000 mg IV every 6 hours OR 650 mg IV every 4 hours

Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 4000 mg per 24 hours

Weight less than 50 kg: 15 mg/kg IV every 6 hours OR 12.5 mg/kg IV every 4 hours

Maximum Single Dose: 15 mg/kg
Minimum Dosing Interval: every 4 hours
Maximum Dose: 75 mg/kg per 24 hours

Comments:

• Maximum daily dose is based on all routes of administration and all products containing paracetamol.
• Maximum daily dose and dosing recommendations may differ by product; some manufacturers have decreased the maximum daily dose to protect consumers from inadvertent overdoses.
• For IV administration, verify the dose in mg and mL to ensure the dose is correct; verify that infusion pumps are properly programmed

Uses:

• For the management of mild to moderate pain and the management of moderate to severe pain with adjunctive opioid analgesics.
• For the reduction of fever.

Usual Pediatric Dose for Pain

Doses may be given as a single or repeated dose as follows:

ORAL:

10 to 15 mg/kg orally every 4 to 6 hours as needed not to exceed 5 doses in 24 hours
-Alternatively, use weight first, then age:
2.7 to 5.3 kg (0 to 3 months): 40 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
5.4 to 8.1 kg (4 to 11 months): 80 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
8.2 to 10.8 kg (12 to 23 months): 120 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
10.9 to 16.3 kg (2 to 3 years): 160 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
16.4 to 21.7 kg (4 to 5 years): 240 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
21.8 to 27.2 kg (6 to 8 years): 320 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
27.3 to 32.6 kg (9 to 10 years): 400 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
32.7 to 43.2 kg (11 to 12 years): 480 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours

12 years or older:

Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours

Extended-Release: 1300 mg orally every 8 hours
Maximum dose: 3900 mg per 24 hours

RECTAL:

6 to 11 months: 80 mg rectally every 6 hours up to a maximum of 4 doses in 24 hours
12 to 36 months: 80 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
3 to 6 years: 120 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
6 to 12 years: 325 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
12 years or older: 650 mg rectally every 4 to 6 hours up to a maximum of 6 doses in 24 hours

PARENTERAL:

2 to 12 years: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg

13 years or older; weight less than 50 kg: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg

13 years or older; weight 50 kg or greater: 650 mg IV every 4 hours OR 1000 mg IV every 6 hours
Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 4000 mg in 24 hours

Comments:

• Maximum daily dose is based on all routes of administration and all products containing paracetamol.
• Maximum daily dose and dosing recommendations may differ by product; some manufacturers have decreased the maximum daily dose to protect consumers from inadvertent overdoses.
• For IV administration, verify the dose in mg and mL to ensure the dose is correct; verify that infusion pumps are properly programmed.

Uses:

For the management of mild to moderate pain and for the management of moderate to severe pain when used with adjunctive opioid analgesics.

Usual Pediatric Dose for Fever

Doses may be given as a single or repeated dose as follows:

ORAL:

10 to 15 mg/kg orally every 4 to 6 hours as needed not to exceed 5 doses in 24 hours
-Alternatively, use weight first, then age:
2.7 to 5.3 kg (0 to 3 months): 40 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
5.4 to 8.1 kg (4 to 11 months): 80 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
8.2 to 10.8 kg (12 to 23 months): 120 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
10.9 to 16.3 kg (2 to 3 years): 160 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
16.4 to 21.7 kg (4 to 5 years): 240 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
21.8 to 27.2 kg (6 to 8 years): 320 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
27.3 to 32.6 kg (9 to 10 years): 400 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours
32.7 to 43.2 kg (11 to 12 years): 480 mg orally every 4 hours as needed not to exceed 5 doses in 24 hours

12 years or older:

Immediate-release: 325 mg to 1 g orally every 4 to 6 hours
Minimum Dosing Interval: every 4 hours
Maximum Single Dose: 1000 mg
Maximum Dose: 4 g per 24 hours

RECTAL:

6 to 11 months: 80 mg rectally every 6 hours up to a maximum of 4 doses in 24 hours
12 to 36 months: 80 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
3 to 6 years: 120 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
6 to 12 years: 325 mg rectally every 4 to 6 hours up to a maximum of 5 doses in 24 hours
12 years or older: 650 mg rectally every 4 to 6 hours up to a maximum of 6 doses in 24 hours

PARENTERAL:

Neonates (premature neonates born at least 32 weeks gestational age up to 28 days chronological age): 12.5 mg/kg IV every 6 hours
Minimum Dosing Interval: 6 hours
Maximum Daily Dose: 50 mg/kg/day

Infants (29 days to 2 years old): 15 mg/kg every 6 hours
Minimum Dosing Interval: 6 hours
Maximum Daily Dose: 60 mg/kg/day

2 to 12 years: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg

13 years or older; weight less than 50 kg: 12.5 mg/kg IV every 4 hours OR 15 mg/kg IV every 6 hours
Maximum Single Dose: 15 mg/kg; not to exceed 750 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 75 mg/kg in 24 hours; not to exceed 3750 mg

13 years or older; weight 50 kg or greater: 650 mg IV every 4 hours OR 1000 mg IV every 6 hours
Maximum Single Dose: 1000 mg
Minimum Dosing Interval: every 4 hours
Maximum Daily Dose: 4000 mg in 24 hours

Comments:

-Maximum daily dose is based on all routes of administration and all products containing paracetamol.
-Maximum daily dose and dosing recommendations may differ by product; some manufacturers have decreased the maximum daily dose to protect consumers from inadvertent overdoses.
-For IV administration, verify the dose in mg and mL to ensure the dose is correct; verify that infusion pumps are properly programmed.

Use: For the reduction of fever.

Renal Dose Adjustments

Severe renal impairment (Creatinine Clearance less than 30 mL/min): Longer dosing intervals and a reduced total daily dose may be warranted

Liver Dose Adjustments

Parenteral:

Severe hepatic impairment, severe active hepatic disease: Use is contraindicated
Mild to moderate hepatic impairment, mild to moderate active hepatic disease: Use with caution; a reduced total daily dose may be warranted

Over the counter products must contain labeling that states:

This product contains paracetamol. Severe liver damage may occur if:

• Adult takes more than maximum daily dose in 24 hours
• Child takes more than 5 doses in 24 hours
• More than 3 alcoholic drinks are consumed per day while using this product.

Dose Adjustments

Use caution in patients with alcoholism, chronic malnutrition, severe hypovolemia (e.g. due to dehydration or blood loss); A reduced daily dose may be warranted.

Suspected Overdose:

• If an overdose is suspected, obtain a serum drug level as soon as possible, but no sooner than 4 hours after oral ingestion.
• Liver function studies should be obtained and repeated at 24-hour intervals.
• The antidote, N-acetylcysteine (NAC) should be administered as soon as possible according to NAC protocols.

How should paracetamol be used?

Paracetamol comes as a tablet, chewable tablet, capsule, suspension or solution (liquid), extended-release (long-acting) tablet, and orally disintegrating tablet (tablet that dissolves quickly in the mouth), to take by mouth, with or without food. Paracetamol also comes as a suppository to use rectally. Paracetamol is available without a prescription, but your doctor may prescribe paracetamol to treat certain conditions. Follow the directions on the package or prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

If you are giving paracetamol to your child, read the package label carefully to make sure that it is the right product for the age of the child. Do not give children paracetamol products that are made for adults. Some products for adults and older children may contain too much paracetamol for a younger child. Check the package label to find out how much medication the child needs. If you know how much your child weighs, give the dose that matches that weight on the chart. If you don’t know your child’s weight, give the dose that matches your child’s age. Ask your child’s doctor if you don’t know how much medication to give your child.

Paracetamol comes in combination with other medications to treat cough and cold symptoms. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using two or more products at the same time. These products may contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.

Swallow the extended-release paracetamol tablets whole; do not split, chew, crush, or dissolve them.

Place the orally disintegrating tablet (‘Meltaways’) in your mouth and allow to dissolve or chew it before swallowing.

Shake the suspension well before each use to mix the medication evenly. Always use the measuring cup or syringe provided by the manufacturer to measure each dose of the solution or suspension. Do not switch dosing devices between different products; always use the device that comes in the product packaging.

Taking paracetamol with other medicines, food and alcohol

Paracetamol can react unpredictably with certain other medications. This can affect how well either medicine works and might increase the risk of side effects.

It may not be safe to take paracetamol at the same time as:

• other products containing paracetamol – including combination products where paracetamol is one of the ingredients
• carbamazepine – used to treat epilepsy and some types of pain
• colestyramine – used to reduce itchiness caused by primary biliary cirrhosis (a type of liver disease)
• imatinib and busulfan – used to treat certain types of cancer
• ketoconazole – a type of antifungal medicine
• lixisenatide – used to treat type 2 diabetes
• metoclopramide – used to relieve nausea and vomiting
• phenobarbital, phenytoin and primidone – used to control seizures
• warfarin – used to prevent blood clots

Check the leaflet that comes with your medicine to see if it can be taken with paracetamol. Ask a pharmacist or doctor if you’re not sure.

There are no known problems caused by taking paracetamol with any specific foods or by drinking moderate amounts of alcohol while taking paracetamol.

Paracetamol side effects

Paracetamol may cause side effects, but side effects from paracetamol are rare, but can include:

• an allergic reaction, which can cause a rash and swelling
• flushing, low blood pressure and a fast heartbeat – this can sometimes happen when paracetamol is given in hospital into a vein in your arm
• blood disorders, such as thrombocytopenia (low number of platelet cells) and leukopenia (low number of white blood cells)
• liver and kidney damage if you take too much (overdose) – this can be fatal in severe cases

Speak to a pharmacist or doctor if you develop any troublesome side effects that you think could be caused by paracetamol.

Some side effects of paracetamol can be serious. If you experience any of the following symptoms, stop taking paracetamol and call your doctor immediately or get emergency medical attention:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• rash
• hives
• itching
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• difficulty breathing or swallowing

Paracetamol may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

Human Exposure and Toxicity

Nausea, vomiting, and abdominal pain usually occur within 2-3 hours after ingestion of toxic doses of the drug paracetamol. In severe poisoning, central nervous system (CNS) stimulation, excitement, and delirium may occur initially. This may be followed by CNS depression, stupor, hypothermia, marked prostration, rapid shallow breathing, rapid weak irregular pulse, low blood pressure, and circulatory failure. When an individual has ingested a toxic dose of paracetamol, the individual should be hospitalized for several days of observation, even if there are no apparent ill effects, because maximum liver damage and/or cardiotoxic effects usually do not become apparent until 2-4 days after ingestion of the drug. Other symptoms of acute poisoning include cerebral edema and nonspecific myocardial depression. Vascular collapse results from the relative hypoxia and from a central depressant action that occurs only with massive doses. Shock may develop if vasodilation is marked. Fatal seizures may occur. Coma usually precedes death, which may occur suddenly or may be delayed for several days. Biopsy of the liver reveals centralobular necrosis with sparing of the periportal area. There have been reports of acute myocardial necrosis and pericarditis in individuals with paracetamol poisoning. Hypoglycemia, which can progress to coma have been reported in patients ingesting toxic doses of paracetamol. Low prothrombin levels and thrombocytopenia have been reported in patients with paracetamol poisoning. Skin reactions of an erythematous or urticarial nature which may be accompanied by fever and oral mucosal lesions also have been reported. For use anytime during pregnancy, 781 exposures were recorded, and possible associations with congenital dislocation of the hip (eight cases) and clubfoot (six cases) were found. There is inadequate evidence in humans for the carcinogenicity of paracetamol.

Evidence for Carcinogenicity

There is inadequate evidence in humans for the carcinogenicity of paracetamol. There is inadequate evidence in experimental animals for the carcinogenicity of paracetamol ². Overall evaluation: Paracetamol is not classifiable as to its carcinogenicity to humans (Group 3) ².

Animal Toxicity Studies

Concern has been raised over chemical-induced disruption of ovary development during fetal life resulting in long-lasting consequences only manifesting themselves much later during adulthood. A growing body of evidence suggests that prenatal exposure to the mild analgesic acetaminophen/paracetamol can cause such a scenario ³. In a review of three recent reports that collectively indicate that prenatal exposure in a period of 13.5 days post coitum in both rats and mouse can result in reduced female reproductive health. The combined data show that the exposure results in the reduction of primordial follicles, irregular menstrual cycle, premature absence of corpus luteum, as well as reduced fertility, resembling premature ovarian insufficiency syndrome in humans that is linked to premature menopause ³. This could especially affect the Western parts of the world, where the age for childbirth is continuously being increased and paracetamol is recommended during pregnancy for pain and fever ³. The study authors highlight an urgent need for more studies to verify these data including both experimental and epidemiological approaches ³.

There is inadequate evidence in experimental animals for the carcinogenicity of paracetamol. In rats fasted 24 hours and given a single dose of paracetamol (2 g/kg) by gavage, liver necrosis around the central vein was noted at 9-12 hours and was much more extensive at 24 hours after treatment. In mice after dietary exposure to paracetamol up to 6400 mg/kg daily for 13 weeks hepatotoxicity, organ weight changes and deaths were observed. Cats are particularly susceptible to paracetamol intoxication, developing more diffuse liver changes, while hepatic centrilobular lesions found in dogs. High doses of paracetamol caused testicular atrophy and delay in spermiogenesis in mice. Furthermore, reductions in the fertility and neonatal survival in mice were seen in the F0 generation and decreases in F1 pup weights were found at paracetamol dose 1430 mg/kg. Paracetamol was not mutagenic in Salmonella typhimurium assay with or without metabolic activation in six strains: TA1535, TA1537, TA1538, TA100, TA97 and TA98. In vitro and animal data indicate that small quantities of paracetamol are metabolized by a cytochrome P-450 microsomal enzyme to a reactive intermediate metabolite (N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI) which is further metabolized via conjugation with glutathione and ultimately excreted in urine as a mercapturic acid. It has been suggested that this intermediate metabolite is responsible forparacetamol-induced liver necrosis in cases of overdose. Excipients found in liquid formulations of paracetamol may decrease its liver toxicity.

Ecotoxicity Studies

Daphnia magna was the most susceptible among the test organisms to the environmental effects of paracetamol. Paracetamol has recently been identified as a promising snake toxicant to reduce brown tree snake populations on Guam, while posing only the minimal risks to non-target rodents, cats, pigs and birds.

Paracetamol poisoning

Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large doses of paracetamol (e.g., 7.5-10 g daily for 1-2 days), or from chronic ingestion of the drug ⁴. Dose-dependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and is potentially fatal ⁴.

A case report of oral paracetamol toxicity in a term newborn infant successfully treated with a 20 hr intravenous N-acetylcysteine infusion protocol without any adverse effects. This case report supports the use of N-acetylcysteine to treat neonatal paracetamol toxicity ⁵.

A 3.5 yr old girl with an upper respiratory infection died of an paracetamol overdose ⁶. When the child’s temperature remained elevated after treatment with 120 mg every 4 hr for 3 doses, dosage was increased to 720 mg every 3 hr. Over the next 24 hr the patient received 5.04 g ⁶.

A 63 yr old man with acute psittacosis had severe hepatic damage after ingesting about 10 g paracetamol over a 48 hr period. Transaminase levels showed striking elevation, with a serum glutamic-oxaloacetic transaminase level of over 15000 iu/L, and decreased rapidly, consistent with toxic insult. The liver showed severe central necrosis at autopsy ⁷.

An 18-year-old woman, gravida 1, presented at 33 weeks’ gestation with signs and symptoms consistent with acute fatty liver of pregnancy and fetal death. Markedly elevated transaminases prompted a search for other etiologies, and paracetamol toxicity was diagnosed. Liver biopsy revealed acute fatty liver of pregnancy and toxin-induced injury consistent with paracetamol use. The patient’s condition deteriorated, resulting in fulminant hepatic failure and requiring postpartum orthotopic liver transplantation. The combination of acute fatty liver of pregnancy and paracetamol toxicity resulted in acute liver failure ⁸.

A case involving a 22-year-old woman in her 31st week of pregnancy who consumed a 15 g dose of paracetamol, followed by a 50 g dose 1 week later is reported ⁹. Fetal distress was observed 16 hours after the second overdose, as evidenced by complete lack of fetal movements and breathing, a marked decrease in fetal heart rate beat-to-beat variability with no accelerations, and a falling baseline rate. Because of the fetal condition, labor was induced (cesarean section was excluded because of the mothers incipient hepatic failure). Eighty-four hours after the overdose, a 2198 g female infant was delivered with an Apgar scores at 1 and 5 min of 9 and 10, respectively. Except for hypoglycemia, mild respiratory disease, and mild jaundice, the newborn did well. Liver enzymes were always within normal range, and the jaundice was compatible with immaturity. Paracetamol was not detected in the cord blood. Follow-up examinations of the infant at 6 weeks and again at 6 months were normal. Protection against serious or permanent liver damage was probably afforded by the prompt administration of iv N-acetylcysteine ⁹.

Nausea, vomiting, and abdominal pain usually occur within 2-3 hours after ingestion of toxic doses of the drug. Unlike aspirin, paracetamol does not usually cause acid/base changes in toxic doses ⁴. In severe poisoning, CNS stimulation, excitement, and delirium may occur initially. This may be followed by CNS (central nervous system) depression; stupor; hypothermia; marked prostration; rapid, shallow breathing; rapid, weak, irregular pulse; low blood pressure; and circulatory failure. Vascular collapse results from the relative hypoxia and from a central depressant action that occurs only with massive doses. Shock may develop if vasodilation is marked. Fatal asphyxial seizures may occur. Coma usually precedes death, which may occur suddenly or may be delayed for several days ⁴.

Paracetamol toxicity usually involves 4 phases ⁴:

1. Anorexia, nausea, vomiting, malaise, and diaphoresis (which inappropriately may prompt administration of additional paracetamol);
2. Resolution of phase-1 manifestations and replacement with right upper quadrant pain or tenderness, liver enlargement, elevated bilirubin and hepatic enzyme concentrations, prolongation of prothrombin time, and occasionally oliguria;
3. Anorexia, nausea, vomiting, and malaise recur (usually 3-5 days after initial symptom onset) and signs of hepatic failure (e.g., jaundice, hypoglycemia, coagulopathy, encephalopathy) and possibly renal failure and cardiomyopathy develop; and
4. Recovery or progression to fatal complete liver failure.

Three hundred and seven cases of liver injury associated with paracetamol use were reported to the US Food and Drug Administration (FDA) from January 1998 to July 2001 ¹⁰. Sixty percent of these adverse events were categorized as severe life-threatening injury with liver failure (category 4); 40% of patients died. Review of these case reports indicates that use of higher than recommended daily dosages of paracetamol results in adverse hepatotoxic effects more often than use of recommended dosages ¹⁰.

The Rocky Mountain Poison and Drug Center ⁹ reported the results of a nationwide study on paracetamol overdose during pregnancy involving 113 women. Of the 60 cases that had appropriate laboratory and pregnancy outcome data, 19 occurred in the 1st trimester, 22 during the 2nd trimester, and 19 during the 3rd trimester. In those cases with a potentially toxic serum level of paracetamol, early treatment with N-acetylcysteine was statistically associated with an improved pregnancy outcome by lessening the incidence of spontaneous abortion and fetal death ⁹. Only one congenital anomaly was observed in the series and that involved a 3rd trimester overdose with nontoxic maternal paracetamol serum levels ⁹.

Very high levels of paracetamol can cause lactic acidosis and altered mental status by uncertain mechanisms, probably involving mitochondrial dysfunctin ¹¹. Symptoms of acute paracetamol poisoning both metabolic acidosis and metabolic alkalosis have been noted; cerebral edema & nonspecific myocardial depression have also occurred ¹². Biopsy of the liver reveals centralobular necrosis with sparing of the periportal area ¹².

Low prothrombin levels have been reported in patients with paracetamol poisoning and in one patient fatal GI hemorrhage was attributed to hypoprothrombinemia. Thrombocytopenia also has been reported. Toxic doses of p-aminophenol derivatives may produce skin reactions of an erythematous or urticarial nature which may be accompanied by fever and oral mucosal lesions ¹³.

Eighty-eight patients with paracetamol-induced acute liver failure were recruited ¹⁴. Control groups included patients with non-paracetamol-induced acute liver failure (n = 13), nonhepatic multiple organ failure (n = 28), chronic liver disease (n = 19), and healthy controls (n = 11). Total and caspase-cleaved cytokeratin-18 (M65 and M30) measured at admission and sequentially on days 3, 7, and 10 following admission. Levels were also determined from hepatic vein, portal vein, and systemic arterial blood in seven patients undergoing transplantation. Protein arrays of liver homogenates from patients with paracetamol-induced acute liver failure were assessed for apoptosis-associated proteins, and histological assessment of liver tissue was performed. Admission M30 levels were significantly elevated in paracetamol-induced acute liver failure and non-paracetamol induced acute liver failure patients compared with multiple organ failure, chronic liver disease, and healthy controls. Admission M30 levels correlated with outcome with area under receiver operating characteristic of 0.755. Peak levels in patients with acute liver failure were seen at admission then fell significantly but did not normalize over 10 days. A negative gradient of M30 from the portal to hepatic vein was demonstrated in patients with paracetamol-induced acute liver failure at the time of liver transplant. Analysis of protein array data demonstrated lower apoptosis-associated protein and higher catalase concentrations in paracetamol-induced acute liver failure compared with controls. Explant histological analysis revealed evidence of cellular proliferation with an absence of histological evidence of apoptosis. Hepatocellular apoptosis occurs in the early phases of human paracetamol-induced acute liver failure, peaking on day 1 of hospital admission, and correlates strongly with poor outcome. Hepatic regenerative/tissue repair responses prevail during the later stages of acute liver failure where elevated levels of M30 are likely to reflect epithelial cell death in extrahepatic organs ¹⁴.

The U.S. Food and Drug Administration (FDA) is informing the public that paracetamol has been associated with a risk of rare but serious skin reactions. These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal ¹⁵. Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur with the use of drug products that contain paracetamol. These reactions can occur with first-time use of paracetamol or at any time while it is being taken. … Anyone who develops a skin rash or reaction while using paracetamol or any other pain reliever/fever reducer should stop the drug and seek medical attention right away. Anyone who has experienced a serious skin reaction with paracetamol should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers. Health care professionals should be aware of this rare risk and consider paracetamol, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions.

Paracetamol overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. You can call 24 hours a day, 7 days a week.

Can you overdose on paracetamol?

Yes. Taking too much paracetamol, known as an overdose, can be very dangerous.

If you’ve taken more than the recommended maximum dose, go to your nearest accident and emergency (A&E) department as soon as possible.

It can be helpful to take any remaining medicine and the box or leaflet with you to a hospital accident and emergency department if you can.

Some people feel sick, vomit or have abdominal (tummy) pain after taking too much paracetamol, but often there are no obvious symptoms at first.

• Go to a hospital accident and emergency department even if you’re feeling well.

When an individual has ingested a toxic dose of acetaminophen, the individual should be hospitalized for several days of observation, even if there are no apparent ill effects, because maximum liver damage usually does not become apparent until 2-4 days after ingestion of the drug ¹³. Transient azotemia and renal tubular necrosis have been reported in patients with acetaminophen poisoning; renal failure is often associated with fatality. There have been reports of acute myocardial necrosis and pericarditis in individuals with acetaminophen poisoning. Maximum cardiotoxic effects of these drugs appear to be delayed in a manner similar to hepatotoxic effects. Hypoglycemia, which can progress to coma, and metabolic acidosis have been reported in patients ingesting toxic doses of acetaminophen and cerebral edema occurred in one patient ¹³.

In acute paracetamol overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. Plasma paracetamol levels > 300 ug/mL at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 150 ug/mL or < 37.5 ug/mL at 12 hours after ingestion. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion ¹⁶.

References

1. Trettin A, Böhmer A, Suchy M-T, et al. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS. Oxidative Medicine and Cellular Longevity. 2014;2014:212576. doi:10.1155/2014/212576. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988730/
2. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. http://monographs.iarc.fr/ENG/Classification/index.php
3. Is exposure during pregnancy to acetaminophen/paracetamol disrupting female reproductive development? Endocr Connect. 2018, Jan; 7(1):149-158.
4. American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 2209
5. Walls L et al; J Perinatol 27 (2): 133-5; 2007
6. Nogen A, Bremmer J; J Pediatr 92 (MAY): 832; 1978
7. Davis AM et al; Am J Med 74 (2): 349; 1983
8. Gill EJ t al; J Reprod Med 47 (7): 584-6; 2002
9. Briggs, G.G., Freeman, R.K., Yaffee, S.J.; Drugs in Pregancy and Lactation Nineth Edition. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, PA. 2011, p. 9
10. American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 2211
11. OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 69
12. Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 704
13. American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 2210
14. Possamai LA et al; Crit Care Med 41 (11): 2543-50; 2013
15. US FDA; FDA Drug Safety Communication: FDA Warns of Rare but Serious Skin Reactions with the Pain Reliever/Fever Reducer Acetaminophen. https://www.fda.gov/drugs/drugsafety/ucm363041.htm
16. US Natl Inst Health; DailyMed. Current Medication Information for OFIRMEV (acetaminophen) injection, solution (October 2013). Available from, as of March 6, 2014

What is adenosine

Adenosine is a ribonucleoside that is composed of adenine bound to ribose with vasodilatory, antiarrhythmic and analgesic activities. Adenosine treats arrhythmias (uneven heartbeat) and is also used during a heart stress test. Adenosine injection is used in combination with Thallium-201 as a pharmacologic stress agent for myocardial perfusion scintigraphy in patients unable to undergo adequate exercise stress. This medicine works by dilating the arteries (vasodilator) of the heart and increase blood flow to help identify coronary artery disease. Adenosine is to be given only by or under the direct supervision of a doctor.

Adenosine has far-reaching effects as an extracellular signaling molecule inducing vasodilation in most vascular beds, regulating activity in the sympathetic nervous system, having antithrombotic properties, and reducing blood pressure and heart rate ¹. Such properties are some of the reasons why adenosine and its derivatives have therapeutic effects in most organ systems.

One of the most common reasons for using adenosine in the cardiovascular system is for the production of vasodilation in the coronary microcirculation to produce hyperemia ². This property of adenosine to modify microcirculatory function has been used for diagnostic and therapeutic effects for many years and is widely adopted as the gold-standard method of diagnosing ischemia invasively and noninvasively.

Adenosine is a white crystalline powder. Adenosine is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH. Adenosine is not chemically related to other antiarrhythmic drugs. Adenosine injection, USP (United States Pharmacopeia) is a sterile, nonpyrogenic solution for rapid bolus intravenous injection. Each mL contains 3 mg Adenosine and 9 mg sodium chloride in water for injection. The pH of the solution is between 4.5 and 7.5.

• Adenosine is used to treat certain types of abnormal heartbeats.
• Adenosine is used during a stress test of the heart.
• Adenosine may be given to you for other reasons. Talk with the doctor.

Adenosine is a naturally occurring endogenous purine nucleoside composed of an adenine molecule attached to a ribose sugar moiety ³ (ribofuranose) via a beta-N9-glycosidic bond (6-amino-9-β-d-ribofuranosyl-9-H-purine). It is the nucleoside base of both adenosine triphosphate (ATP) and the signaling molecule cyclic adenosine monophosphate (cAMP). Adenosine is rapidly transported into vascular endothelial cells and erythrocytes where it is catabolized by adenosine deaminase to inosine ⁴. Dipyridamole, a commonly used vasoactive medication ⁵ exerts its effects through inhibition of adenosine deaminase. Adenosine is (re)phosphorylated by adenine kinase forming adenosine monophosphate, which is incorporated into the high-energy phosphate pool ⁶. Adenosine levels can rise rapidly in ischemic tissue due to adenosine kinase inhibition ³.

Adenosine is also a naturally occurring breakdown product of adenosine triphosphate (ATP), which is hydrolyzed and dephosphorylated to produce adenosine ⁷. Adenosine may be produced inside the cells (intracellular) by the action of enzyme 5′-nucleotidase on 5′-AMP. On the other hand, adenosine in the extracellular space is formed by the action of enzyme ecto-5′ nucleotidase ⁸. Apart from a simple degradation product, adenosine produces multiple physiological effects such as regulation of blood flow, heart rate and heart contractility through activation of different adenosine receptors ⁹. Four types of adenosine receptors, A₁, A_2A, A_2B and A₃ have been identified and all are G-protein coupled receptors. The A₁ and A₃ are G_i-coupled receptors that inhibit adenylyl cyclase activity and cAMP production; whereas, A_2A and A_2B are G_s-coupled receptors that activates adenylyl cyclase and cAMP production. Furthermore, A_2B receptors also couple to G_q proteins to activate phospholipase C ¹⁰. Adenosine receptors are widely expressed in the body. The A₁ receptors are highly expressed throughout the CNS (central nervous system – brain and spinal cord), heart muscles and in inflammatory cells ¹¹. The A₂ receptors are located in pre- and postsynaptic nerve terminals, mast cells, heart (smooth muscle and endothelial cells) and in circulating leukocytes. A₃ receptors are found in the heart (endothelial cells of the aorta, smooth muscle cells), kidney, testis, mast cells, eosinophils, neutrophils and in brain cortex ¹².

Adenosine triphosphate (ATP) is at the root of all organisms energetics. Adenosine triphosphate (ATP) provides the energy for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. It is estimated that the human body uses roughly 2 × 10²⁶ transient molecules of ATP or more than the bodies weight; 160 kg of ATP in a day ¹³. Adenosine triphosphate (ATP) stores energy in a high energy phosphate bond, the third phosphate bond. The cutting of one phosphate bond, ATP + H₂O → ADP + Pi liberates about 30.6 kJ/mole ¹³.

Adenosine diphosphate (ADP) is a platelet agonist that is stored in platelet-dense granules. When a platelet is activated, ADP is released and binds to platelet surface receptors, P2Y₁ and P2Y₁₂, thus recruiting additional platelets to form a platelet plug. Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel (Plavix®) and ticlopidine (Ticlid®) prevent platelet aggregation by selectively and irreversibly binding the platelet surface receptor P2Y₁₂. Platelet aggregation is inhibited for the remainder of the platelet lifespan (7–10 days). Clopidogrel is indicated for treatment of acute ST and non-ST elevation myocardial infarction, peripheral arterial disease, arteriosclerotic vascular disease, and stroke. Ticlopidine is indicated after placement of coronary stents and after thromboembolic stroke ¹⁴.

Proper use of adenosine

A nurse or other trained health professional will give you adenosine. Adenosine is given through a needle placed into one of your veins.

Precautions while using adenosine

It is very important that your doctor check your progress very closely while you are receiving adenosine. This will allow your doctor to see if adenosine is working properly and to decide if you should continue to receive it.

Heart attack and death may occur after receiving adenosine. Make sure your doctor knows if you have any heart problems (eg, unstable angina or cardiovascular instability) before you have a heart stress test. Check with your doctor right away if you have chest pain or discomfort, nausea, pain or discomfort in arms, jaw, back or neck, sweating, or vomiting.

Do not take anything that contains caffeine before you receive adenosine. This includes medicines, foods, and beverages with caffeine, such as coffee, tea, and cola drinks.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

What do I need to tell my doctor BEFORE I take Adenosine?

• If you have an allergy to adenosine or any other part of adenosine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Certain types of abnormal heartbeats (heart block, sick sinus syndrome) without a working pacemaker.
• If you have a certain type of chest pain (unstable angina).
• If you have any of these health problems: Asthma or other breathing problems like COPD (chronic obstructive pulmonary disease).

This is not a list of all drugs or health problems that interact with adenosine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take adenosine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Side effects of adenosine

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Flushing.
• Headache.
• Belly pain.

More Common

• chest discomfort
• difficult or labored breathing
• lightheadedness or dizziness
• throat, neck, or jaw discomfort
• tightness in the chest

Less Common

• chest pain
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, slow, or irregular heartbeat
• sweating
• troubled breathing
• unusual tiredness or weakness

Rare

• fast, irregular, pounding, or racing heartbeat or pulse
• headache
• nervousness
• pounding in the ears

Some side effects of adenosine may occur that usually do not need medical attention. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them.

Call your doctor right away if you notice any of these side effects:

• Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing
• Chest pain that may spread to your arms, jaw, back, or neck, trouble breathing, nausea, unusual sweating
• Fast, slow, or uneven heartbeat
• Lightheadedness, dizziness, or fainting
• Numbness of weakness on one side of your body, sudden or severe headache, problems with vision, speech, or walking
• Throat, neck, or jaw discomfort, pain, or tightness

Figure 2. Adenosine Metabolism

Before using adenosine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For adenosine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to adenosine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children

Appropriate studies have not been performed on the relationship of age to the effects of adenosine injection in the pediatric population. Safety and efficacy have not been established. However, intravenous adenosine has been used for the treatment of PSVT in neonates, infants, children and adolescents.

Older Adults

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of adenosine injection in the elderly.

Pregnancy

Pregnancy Category C (all Trimesters): Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether adenosine can cause fetal harm when administered to pregnant women, adenosine should be used during pregnancy only if clearly needed.

Breastfeeding

There are no adequate studies in women for determining infant risk when using adenosine during breastfeeding. Weigh the potential benefits against the potential risks before taking adenosine while breastfeeding.

Interactions with other medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving adenosine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using adenosine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminophylline
• Carbamazepine
• Dimenhydrinate
• Dyphylline
• Pentoxifylline
• Theophylline
• Verapamil

Intravenous adenosine injection has been effectively administered in the presence of other cardioactive drugs, such as quinidine, beta-adrenergic blocking agents, calcium channel blocking agents, and angiotensin converting enzyme inhibitors, without any change in the adverse reaction profile. Digoxin and verapamil use may be rarely associated with ventricular fibrillation when combined with Adenosine (see Warnings). Because of the potential for additive or synergistic depressant effects on the SA (sinoatrial node) and AV (atrioventricular) nodes, however, Adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving digitalis may be rarely associated with ventricular fibrillation.

Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.

Using adenosine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Dipyridamole

Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of Adenosine may be effective in the presence of dipyridamole.

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using adenosine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Caffeine

The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective.

Other Medical Problems

The presence of other medical problems may affect the use of adenosine. Make sure you tell your doctor if you have any other medical problems, especially:

• Angina, unstable or
• Unstable heart or blood vessel problem (eg, cardiovascular instability)—Avoid use, as adenosine may increase the risk for heart attack.
• Atrial fibrillation (heart rhythm problem), or history of or
• Breathing problems or lung disease (eg, bronchitis, emphysema) or
• Hypertension (high blood pressure) or
• Hypotension (low blood pressure) or
• Seizures or
• Stroke, history of—Use with caution. May make these conditions worse.
• Heart block, second or third degree (type of abnormal heart rhythm), without a pacemaker or
• Sinus node disease (such as sick sinus syndrome), without a pacemaker—Should not be used in patients with these conditions, unless patients have a pacemaker that works.
• Breathing problems or lung disease (e.g., asthma)—Should not be used in patients with these conditions.
• Heart or blood vessel disease (e.g., coronary artery stenosis, ischemia, pericardial effusion, pericarditis) or
• Heart valve disease or
• Hypovolemia (low blood volume), uncorrected—May increase risk for more serious side effects.

What are some things I need to know or do while I take Adenosine?

• Tell all of your health care providers that you take adenosine. This includes your doctors, nurses, pharmacists, and dentists.
• Have an ECG checked often. Talk with your doctor.
• High or low blood pressure may happen with adenosine. Have your blood pressure checked as you have been told by your doctor.
• Avoid use of caffeine (for example, tea, coffee, cola) and chocolate.
• If you are taking aminophylline, dipyridamole, theophylline, or any drug containing caffeine, talk with doctor. These drugs can affect how well adenosine works.
• Heart attacks and very bad fast heartbeat have rarely happened with adenosine. Sometimes this has been deadly. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using adenosine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Adenosine) best taken?

Use adenosine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

It is given as a shot into a vein.

What do I do if I miss a dose?

Call your doctor to find out what to do.

What does adenosine do

Adenosine injection slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome.

Adenosine is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenosine is not blocked by atropine.
Hemodynamics

The intravenous bolus dose of 6 or 12 mg Adenosine usually has no systemic hemodynamic effects. When larger doses are given by infusion, Adenosine decreases blood pressure by decreasing peripheral resistance.

Adenosine Clinical Trial Results

In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with paroxysmal supraventricular tachycardia had converted to normal sinus rhythm within one minute after an intravenous bolus dose of 6 mg Adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1 to 4 placebo bolus injections. Similar responses were seen in a variety of patient subsets, including those using or not using digoxin, those with Wolff-Parkinson-White Syndrome, males, females, blacks, Caucasians, and Hispanics.

Adenosine is not effective in converting rhythms other than PSVT, such as atrial flutter, atrial fibrillation, or ventricular tachycardia, to normal sinus rhythm.

Adenosine Pharmacokinetics

Intravenously administered Adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. Intracellular Adenosine is rapidly metabolized either via phosphorylation to Adenosine monophosphate by Adenosine kinase, or via deamination to inosine by Adenosine deaminase in the cytosol. Since Adenosine kinase has a lower Km and Vmax than Adenosine deaminase, deamination plays a significant role only when cytosolic Adenosine saturates the phosphorylation pathway. Inosine formed by deamination of Adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of Adenosine is incorporated into the high-energy phosphate pool. While extracellular Adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of Adenosine deaminase. As Adenosine requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.

Adenosine contraindications

Adenosine is not right for everyone. You should not receive adenosine if you had an allergic reaction to adenosine, or if you have asthma or certain heart rhythm problems.

Intravenous Adenosine injection is contraindicated in:

1. Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker).
2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker).
3. Known hypersensitivity to Adenosine.

What is adenosine used for

Intravenous Adenosine injection is indicated for the following:

• Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver), should be attempted prior to Adenosine administration.

It is important to be sure the Adenosine injection solution actually reaches the systemic circulation.

Adenosine injection does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following Adenosine administration.

Adenosine dose

Adenosine Injection, USP is supplied as a sterile non-pyrogenic solution in normal saline as follows:

Adenosine Injection, USP (3 mg per mL)	Package Factor
6 mg/2 mL Single-Dose Vial	10 vials per carton
12 mg/4 mL Single-Dose Vial	10 vials per carton

Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature.]

Store upright.

DO NOT REFRIGERATE as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use. Contains no preservatives. Discard unused portion.

The container closure is not made with natural rubber latex.

Sterile, Nonpyrogenic, Preservative-free.

Adult Patients

The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of Adenosine injection has not been systematically studied.

The recommended intravenous doses for adults are as follows:

• Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).
• Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

Pediatric Patients

The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.

Pediatric Patients with a Body Weight < 50 kg:

• Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
• Repeat administration: If conversion of PSVT does not occur within 1 to 2 minutes, additional bolus injections of Adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Pediatric Patients with a Body Weight ≥ 50 kg: Administer the adult dose.

Doses greater than 12 mg are not recommended for adult and pediatric patients.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Adenosine side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

• chest discomfort
• difficult or labored breathing
• lightheadedness or dizziness
• throat, neck, or jaw discomfort
• tightness in the chest

Less common

• chest pain
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, slow, or irregular heartbeat
• sweating
• troubled breathing
• unusual tiredness or weakness

Rare

• fast, irregular, pounding, or racing heartbeat or pulse
• headache
• nervousness
• pounding in the ears

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More Common

• diarrhea
• feeling of warmth
• indigestion
• loss of appetite
• nausea or vomiting
• passing of gas
• redness of the face, neck, arms, and occasionally, upper chest
• stomach pain, fullness, or discomfort

Rare

• area of decreased vision
• cough
• discomfort in the back, ears, or tongue
• drowsiness
• dry mouth
• metallic taste
• mood changes
• shakiness in the legs, arms, hands, or feet
• stuffy nose
• trembling or shaking of the hands or feet

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

Side effects that applies to adenosine: compounding powder, intravenous solution, sublingual spray

General

The most common adverse reactions are flushing, chest discomfort, dyspnea, facial flushing, headache, throat/neck/jaw discomfort, gastrointestinal discomfort, and lightheadedness/dizziness.

Cardiovascular

• Very common (10% or more): Flushing (44%), facial flushing (18%)
• Common (1% to 10%): First degree atrioventricular block, second degree atrioventricular block, hypotension, arrhythmias, ventricular tachycardia
• Uncommon (0.1% to 1%): Bradycardia, sinus tachycardia, palpitations
• Very rare (less than 0.01%): Atrial fibrillation, ventricular fibrillation, Torsade de pointes, severe bradycardia
• Frequency not reported: Myocardial infarction, ventricular arrhythmia, third degree atrioventricular block, sinus exit block, sinus pause, hypertension, skipped beats, atrial extrasystoles, ventricular extrasystoles
• Postmarketing reports: Cardiac arrest/asystole, cardiac failure, tachycardia, prolonged asystole, transient increase in blood pressure

Other side effects

• Very common (10% or more): Chest discomfort (40%)
• Common (1% to 10%): ST segment depression, chest pressure
• Uncommon (0.1% to 1%): Feeling of general discomfort/weakness/pain
• Rare (less than 0.1%): Tinnitus, nipple discomfort
• Frequency not reported: Chest pain, feeling of thoracic constriction/oppression, weakness, T wave changes, ear discomfort, tongue discomfort, heaviness in arms, pressure in groin
• Postmarketing reports: ST segment elevation

Respiratory

• Very common (10% or more): Dyspnea (up to 28%)
• Uncommon (0.1% to 1%): Hyperventilation
• Rare (0.01% to 0.1%): Bronchospasm, nasal congestion
• Very rare (less than 0.01%): Respiratory failure
• Frequency not reported: Cough, throat tightness
• Postmarketing reports: Respiratory arrest/apnea

Nervous system

• Very common (10% or more): Headache (up to 18%), lightheadedness/dizziness (12%)
• Common (1% to 10%): Paresthesia, tingling in arms, numbness, burning sensation
• Uncommon (0.1% to 1%): Metallic taste, head pressure
• Rare (0.01% to 0.1%): Tremor, drowsiness
• Very rare (less than 0.01%): Intracranial hypertension worsening
• Frequency not reported: Scotomas, convulsions
• Postmarketing reports: Cerebrovascular accident, intracranial hemorrhage, seizure, tonic clonic seizures, loss of consciousness/syncope

Musculoskeletal

Very common (10% or more): Throat/neck/jaw discomfort (15%)

Common (1% to 10%): Upper extremity discomfort

Frequency not reported: Back discomfort, lower extremity discomfort, neck and back pain

Gastrointestinal

Very common (10% or more): Gastrointestinal discomfort (13%)

Common (1% to 10%): Dry mouth, nausea

Frequency not reported: Abdominal discomfort

Postmarketing reports: Vomiting

Psychiatric

Common (1% to 10%): Nervousness, apprehension

Frequency not reported: Emotional instability

Dermatologic

Uncommon (0.1% to 1%): Sweating

Postmarketing reports: Angioedema, urticaria, rash

Ocular

Uncommon (0.1% to 1%): Blurred vision

Genitourinary

Rare (less than 0.1%): Urinary urgency

Frequency not reported: Vaginal pressure

Local

Very rare (less than 0.01%): Injection site reaction

Postmarketing reports: Infusion site pain

Hypersensitivity

Postmarketing reports: Hypersensitivity, anaphylaxis

Serious side effects

Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Chest pain or pressure.
• Fast or slow heartbeat.
• A heartbeat that does not feel normal.
• Shortness of breath.
• Seizures.
• Throat, neck, or jaw pain.

Adenosine Adverse Reactions

The following reactions were reported with intravenous Adenosine injection used in controlled U.S. clinical trials. The placebo group had a less than 1% rate of all of these reactions.

Cardiovascular

Facial flushing (18%), headache (2%), sweating, palpitations, chest pain, hypotension (less than 1%).

Respiratory

Shortness of breath/dyspnea (12%), chest pressure (7%), hyperventilation, head pressure (less than 1%).

Central Nervous System

Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).

Gastrointestinal

Nausea (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).

Post Marketing Experience (see Warnings)

The following adverse events have been reported from marketing experience with Adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.

Cardiovascular

Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillation, and Torsade de Pointes.

Respiratory

Bronchospasm

Central Nervous System

Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.

Adenosine Overdose

The half-life of adenosine injection is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting. Treatment of any prolonged adverse effects should be individualized and be directed toward the specific effect. Methylxanthines, such as caffeine and theophylline, are competitive antagonists of Adenosine.

References

1. Adenosine: Physiology, Pharmacology, and Clinical Applications. JACC: Cardiovascular Interventions Volume 7, Issue 6, June 2014, Pages 581-591 https://ac.els-cdn.com/S1936879814006323/1-s2.0-S1936879814006323-main.pdf?_tid=56b2f949-90e2-414c-bd77-3fda8baea8d2&acdnat=1530881194_ba45771fb1415199fc0fa525de108b47
2. The crux of maximum hyperemia: the last remaining barrier for routine use of fractional flow reserve. J Am Coll Cardiol Intv, 4 (2011), pp. 1093-1095
3. Adenosine: an old drug newly discovered. Anesthesiology, 111 (2009), pp. 904-915
4. Involvement of adenosine deaminase and adenosine kinase in regulating extracellular adenosine concentration in rat hippocampal slices. Neurochem Int, 26 (1995), pp. 387-395
5. Dipyridamole stress echocardiography. Cardiol Clin, 17 (1999), pp. 481-499
6. Adenosine kinase and ribokinase–the RK family of proteins. Cell Mol Life Sci, 65 (2008), pp. 2875-2896
7. Singh L, Kulshrestha R, Singh N, Jaggi AS. Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection. The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology. 2018;22(3):225-234. doi:10.4196/kjpp.2018.22.3.225. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928336/
8. Sheth S, Brito R, Mukherjea D, Rybak LP, Ramkumar V. Adenosine receptors: expression, function and regulation. Int J Mol Sci. 2014;15:2024–2052 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958836/
9. Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine: physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv. 2014;7:581–591 https://www.sciencedirect.com/science/article/pii/S1936879814006323
10. Headrick JP, Ashton KJ, Rose’meyer RB, Peart JN. Cardiovascular adenosine receptors: expression, actions and interactions. Pharmacol Ther. 2013;140:92–111 https://www.ncbi.nlm.nih.gov/pubmed/23764371
11. Ohta A, Sitkovsky M. The adenosinergic immunomodulatory drugs. Curr Opin Pharmacol. 2009;9:501–506 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756083/
12. Sachdeva S, Gupta M. Adenosine and its receptors as therapeutic targets: an overview. Saudi Pharm J. 2013;21:245–253 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744929/
13. Adenosine Triphosphate Energetics. Biology of Life Biochemistry, Physiology and Philosophy 2016, Pages 65-77
14. Commonly used drugs in hematologic disorders. Handbook of Clinical Volume 120, 2014, Pages 1125-1139

What is fexofenadine

Fexofenadine is a non-drowsy antihistamine that is used to relieve the symptoms of allergies, hay fever (seasonal allergic rhinitis) and hives of the skin (chronic idiopathic urticaria). Fexofenadine is a second generation antihistamine that is much less likely to make you feel sleepy than some other antihistamines. Fexofenadine is a histamine [H1] receptor blocker, that works by blocking the action of histamine, a substance in the body that causes allergic symptoms. When you come into contact with something you have an allergy to, such as pollen, animal hair or fur, house dust or insect bites, your body produces a chemical called histamine. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Usually histamine is a useful substance but in an allergic reaction it causes unpleasant symptoms including itchy, watery eyes, running or blocked nose, sneezing and skin rashes. Fexofenadine blocks the effects of histamine and so reduces these symptoms.

Fexofenadine is used to treat hay fever (seasonal allergic rhinitis), allergic conjunctivitis (red, itchy eye), itchy throat, eczema and hives of the skin (nettle rash or chronic idiopathic urticaria). Fexofenadine is also used for reactions to insect bites and stings and for some food allergies.

Fexofenadine is available is an over-the- counter (OTC) and also on prescription. It comes as tablets, meltable tablets, capsule and liquid suspension

Key facts

• It’s usual to take fexofenadine once a day. Children sometimes take it twice a day.
• Fexofenadine is classed as a non-drowsy antihistamine, but some people still find it makes them feel quite sleepy.
• Common side effects include headache, feeling sleepy, dry mouth, feeling sick and dizziness.
• Don’t drink grapefruit juice, apple juice or orange juice while you’re taking fexofenadine. It might make you more likely to get side effects.
• It’s best not to drink alcohol while you’re taking fexofenadine as it can make you feel sleepy.
• Fexofenadine is also called by the brand name Telfast, Allegra, Allegra 24 Hour Allergy, Allegra Allergy, Allegra ODT, Aller-Ease, Children’s Allegra Allergy, Children’s Allegra ODT, Allergy Relief (Fexofenadine HCl), Mucinex Allergy, Wal-Fex and Allegra OTC.

How long does it take for fexofenadine to work?

You should start to feel better within an hour or 2.

Can I drink alcohol with fexofenadine?

It’s best not to drink alcohol while you’re taking fexofenadine as it can make you feel sleepy.

Is there any food or drink I need to avoid?

Don’t drink grapefruit juice, orange juice or apple juice while taking fexofenadine. It might make you more likely to have side effects.

Fruit juices can make it harder for your body to absorb fexofenadine. Do not take fexofenadine with fruit juice (such as apple, orange, or grapefruit).

What else should I avoid?

Avoid using antacids within 15 minutes before or after taking a medication that contains fexofenadine. Antacids can make it harder for your body to absorb this medication.

Avoid taking any other cold or allergy medicines unless your doctor has told you to.

What’s the difference between fexofenadine and other antihistamines?

Fexofenadine is known as a non-drowsy antihistamine. That’s because it’s less likely to make you feel sleepy than other, so-called ‘sedating antihistamines’ such as Benadryl or Diphenhydramine.

Most people prefer to take a non-drowsy antihistamine instead of a sedating one. An exception is when you want the medicine to make you sleepy, for example if you have itchy skin that’s keeping you awake at night.

What’s the difference between fexofenadine and other non-drowsy antihistamines?

Other non-drowsy antihistamines like acrivastine, cetirizine (Zyrtec), loratadine (Claritin), desloratadine and levocetirizine seem to work just as well as fexofenadine.

However, fexofenadine seems to be less likely to make you feel sleepy than other non-drowsy antihistamines.

If one non-drowsy antihistamine hasn’t worked for you, it’s worth trying another one.

How long should I take fexofenadine for?

It depends on why you’re taking fexofenadine.

You may only need to take it as a one-off dose or for a day or 2, for example if you have a reaction to an insect bite.

You may need to take fexofenadine for longer if you’re taking it to prevent symptoms – for example, to stop hay fever when the pollen count is high.

Talk to your doctor or pharmacist if you’re unsure how long you need to take fexofenadine for.

Is it safe to take fexofenadine for a long time?

Fexofenadine is unlikely to do you any harm if you take it for a long time. However, it’s best to take fexofenadine only for as long as you need to.

Can I drive or ride a bike with fexofenadine?

Fexofenadine is classed as a non-drowsy antihistamine but it’s still possible to feel sleepy after taking it.

If you’re taking fexofenadine for the first time, see how it makes you feel before driving, cycling or using heavy machinery or tools.

Does fexofenadine cause weight gain?

Fexofenadine isn’t known to cause weight gain.

Can I take fexofenadine with painkillers?

Yes, you can take fexofenadine together with acetaminophen (Tylenol) or ibuprofen (Motrin).

Can I take more than one antihistamine together?

Sometimes doctors recommend that people with a severe itchy skin rash take 2 different antihistamines together for a few days.

As well as taking a non-drowsy antihistamine during the day such as fexofenadine, Zyrtec (Cetirizine) or Claritin (Loratadine), your doctor may suggest that you take a sedating antihistamine (e.g. Benadryl) at night time if the itch is making it difficult to sleep.

Do not take 2 antihistamines together unless your doctor advises you to.

Can I take fexofenadine with other hay fever treatments?

Yes, it’s fine to take fexofenadine together with other hay fever treatments, for example steroid nasal sprays (such as Beconase, Rhinacort Aqua and Flixonase Nasules) or eye drops.

Can I take fexofenadine at higher doses than on the packet?

Your doctor might suggest you or your child take a higher dose of fexofenadine (up to 4 times the usual dose) for a severe itchy skin rash or angioedema (swelling underneath the skin).

Taking high doses of fexofenadine isn’t suitable for everyone. Speak to your doctor if you don’t think fexofenadine is working for you.

Can lifestyle changes relieve hay fever?

It will help if you don’t spend too much time outside if the pollen count is high.

Tips for when you’re outside:

• Don’t cut grass or walk on grass.
• Wear wraparound sunglasses to stop pollen getting into your eyes.
• Put Vaseline around your nostrils to help trap pollen.
• Shower and change your clothes after you’ve been outside to wash off pollen.

Tips for when you’re inside:

• Keep windows and doors shut as much as possible.
• Vacuum regularly and dust with a damp cloth.
• Don’t keep fresh flowers in the house.
• Don’t smoke or be around smoke as it makes hay fever symptoms worse.

Who can and can’t take fexofenadine

Fexofenadine tablets can be taken by adults and children aged 6 years and over.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered.

Fexofenadine isn’t recommended for people over 65 years old because there isn’t much research on the medicine in this age group. Talk to your pharmacist or doctor if you’re over 65 and want to take fexofenadine. Elderly patients are more likely to have age-related kidney problems, which may require an adjustment in the dose for patients receiving fexofenadine.

Fexofenadine isn’t suitable for some people. Tell your doctor or pharmacist if you:

• have had an allergic reaction to fexofenadine or any other medicines in the past. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
• have problems with your liver or kidneys
• have, or have ever had, heart problems
• have epilepsy or another health problem that puts you at risk of seizures
• are booked to have an allergy test – taking fexofenadine may affect the results, so you might need to stop taking it a few days before the test

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Kidney disease — Use with caution. The effects may be increased because of slower removal of the medicine from the body .
• Phenylketonuria (PKU) — Use with caution. The oral disintegrating tablets contain phenylalanine .

Pediatric patients

Appropriate studies have not been performed on the relationship of age to the effects of fexofenadine in children below 6 months of age. Safety and efficacy have not been established.

• Do NOT give fexofenadine to a child without medical advice.

Do not give any cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects.

Fexofenadine Drug Interactions

Tell your doctor or pharmacist if you’re taking any other medicines, including herbal remedies, vitamins or supplements.

Some medicines and fexofenadine interfere with each other and increase the chances of you having side effects. Check with your pharmacist or doctor if you’re taking:

• midodrine, a medicine used to treat low blood pressure
• ketoconazole, a medicine to treat fungal infections
• erythromycin, an antibiotic
• ritonavir or lopinavir, medicines used to treat HIV infection
• rifampicin, an antibiotic
• indigestion remedies containing aluminium or magnesium – leave about 2 hours between the times that you take fexofenadine and your indigestion remedy
• any medicine that makes you drowsy, gives you a dry mouth, or makes it difficult for you to pee. Taking fexofenadine might make these side effects worse.

Using fexofenadine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Eliglustat
• Simeprevir

Using fexofenadine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aluminum Carbonate, Basic
• Aluminum Hydroxide
• Aluminum Phosphate
• Dihydroxyaluminum Aminoacetate
• Dihydroxyaluminum Sodium Carbonate
• Magaldrate
• Magnesium Carbonate
• Magnesium Hydroxide
• Magnesium Oxide
• Magnesium Trisilicate
• St John’s Wort

Mixing fexofenadine with herbal remedies and supplements

There might be a problem taking some herbal remedies and supplements alongside fexofenadine – especially ones that cause sleepiness, a dry mouth or make it difficult to pee.

Before taking fexofenadine – Precautions

• tell your doctor and pharmacist if you are allergic to fexofenadine, any other medications, or any of the ingredients in fexofenadine tablets or suspension. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention either of the following: erythromycin (E.E.S., E-Mycin, Erythrocin) and ketoconazole (Nizoral). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• if you are taking an antacid containing aluminum or magnesium (Maalox, Mylanta, others), take the antacid a few hours before or after fexofenadine.
• tell your doctor if you have or have ever had kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking fexofenadine, call your doctor.

Pregnancy and Breastfeeding

For safety, tell your pharmacist or doctor if you’re trying to get pregnant, are already pregnant or if you’re breastfeeding.

Fexofenadine isn’t normally recommended during pregnancy.

FDA pregnancy category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

It is not known whether fexofenadine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

A similar antihistamine called Loratadine (Claritin) is normally used first because there’s more information to say that it’s safer.

Talk to your doctor about the benefits and possible harms of taking fexofenadine. It will also depend on how many weeks pregnant you are and the reason you need to take fexofenadine.

I just found out I am pregnant. Should I stop taking fexofenadine?

You should always talk with your healthcare provider before making any changes in your medications. It is important to consider the benefits of treating allergy symptoms and other conditions during pregnancy. Treating allergy symptoms may reduce asthma symptoms and the need for additional asthma medicines.

In people who took 60 mg of fexofenadine twice a day, it could take up to 4 days for all of this medication to leave the body.

I am pregnant. Can use of fexofenadine during pregnancy cause birth defects?

So far, studies on both fexofenadine and Terfenadine [terfenadine changes into fexofenadine in the body, so information on terfenadine may also be helpful for predicting the effects of fexofenadine on pregnancy and breastfeeding] have not found an increase in birth defects with use of these medicines ¹, ², ³, ⁴, ⁴, ⁵.

Can fexofenadine cause a miscarriage?

There are no studies that have looked at whether fexofenadine can increase the chance for a miscarriage.

Can use of fexofenadine cause other pregnancy complications?

No studies have looked at whether fexofenadine could cause other pregnancy complications. A study on Terfenadine [terfenadine changes into fexofenadine in the body, so information on terfenadine may also be helpful for predicting the effects of fexofenadine on pregnancy and breastfeeding] found no increase in premature delivery or low birth weight with use during pregnancy.

Will fexofenadine affect my fertility?

There’s no evidence that fexofenadine affects male or female fertility.

Will fexofenadine affect my contraception?

Fexofenadine doesn’t affect any type of contraception, including the contraceptive pill and the morning after pill.

What if the father of the baby takes fexofenadine?

There is no evidence that suggests that a man’s fexofenadine use would cause any problems during his partner’s pregnancy. In general, exposures that fathers have are unlikely to increase risks to a pregnancy.

Fexofenadine and breastfeeding

There’s not a lot of information on the use of fexofenadine during breastfeeding, and so it’s best not to take it.

• Fexofenadine during breastfeeding is not recommended.

It’s usually safe to take similar antihistamines called Loratadine (Claritin) and Cetirizine (Zyrtec) while you’re breastfeeding.

However, speak to your doctor before taking any antihistamine if your baby was premature, had a low birth weight or has other health problems.

It is not known if fexofenadine hydrochloride is distributed into breast milk ⁶. Since there are no adequate and controlled studies to date on the use of fexofenadine during lactation in humans and because many drugs are excreted in human milk, the manufacturer states that fexofenadine alone or in fixed combination with pseudoephedrine hydrochloride should be used with caution in nursing women, and a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman ⁶.

Fexofenadine is less likely to cause sleepiness in adults than some other antihistamines. For this reason, fexofenadine may be preferred for breastfeeding over antihistamines that do cause sleepiness. Information from Terfenadine [terfenadine changes into fexofenadine in the body, so information on terfenadine may also be helpful for predicting the effects of fexofenadine on pregnancy and breastfeeding] suggests that the amount of fexofenadine in the breastmilk is small. One study estimated that a baby that was breastfed by a mother taking fexofenadine got less than 1% of the mother’s dose ⁷. This dose would be too low to cause problems for the baby.

When 25 women were asked by telephone how their babies were doing while they were taking terfenadine and breastfeeding, three mothers said their babies experienced irritability but that they did not need to take the babies to a healthcare provider ⁸. It is not possible to know if their irritability was caused by terfenadine in breastmilk.

It is possible, but not proven, that antihistamines may lower the amount of milk a woman makes. This might be more likely to occur if antihistamines are used in combination with an oral decongestant like pseudoephedrine or phenylephrine, or if used before beginning to breastfeed.

Be sure to talk to your health care provider about all your breastfeeding questions.

Fexofenadine vs Cetirizine

Cetirizine or cetirizine hydrochloride (cetirizine HCL) is a non-drowsy antihistamine medicine that relieves the symptoms of allergies by blocking the effects of the chemical histamine in your body. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Cetirizine is much less likely to make you feel sleepy than some other first generation or older antihistamines. Cetirizine was the first marketed drug from the series of second-generation antihistamines showing both minimal side effects on the central nervous system and a reduced level of cardiotoxicity ⁹.

When you come into contact with something you’re allergic to, such as pollen, animal hair or fur, house dust or insect bites and stings, your body produces a chemical called histamine. Usually histamine is a useful substance but in an allergic reaction it causes unpleasant symptoms including itchy, watery eyes, running or blocked nose, sneezing and skin rashes.

Cetirizine blocks the effects of histamine and reduces these symptoms.

Cetirizine starts to work within 30 – 60 minutes after being taken. You should start to feel better within an hour.

Key facts:

• It’s usual to take cetirizine once a day. Children sometimes take it twice a day.
• Cetirizine is classed as a non-drowsy antihistamine, but some people still find it makes them feel quite sleepy.
• Common side effects include headache, dry mouth, feeling sick, dizziness, tummy pain and diarrhea.
• It’s best not to drink alcohol while you’re taking cetirizine as it can make you feel sleepy.
• Cetirizine is sold under the trade names Benadryl Allergy, Piriteze, Zirtec, Zyrtec, and Reactine.

Cetirizine is available on prescription. You can also buy it from pharmacies and supermarkets.

Cetirizine comes as tablets, capsules and as a liquid that you swallow.

Despite cetirizine is being marketed as a non-drowsy antihistamine, it may still impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of cetirizine.

Tell your doctor if you regularly use other medicines that make you sleepy (such as other cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by cetirizine. Call your doctor if your symptoms do not improve, if they get worse, or if you also have a fever.

Fexofenadine vs Loratadine

Loratadine is a non-drowsy antihistamine (a second generation antihistamine) medicine that relieves the symptoms of allergies. Loratadine is used to treat hay fever, allergic conjunctivitis (red, itchy eye), eczema and hives. Loratadine is also used for reactions to insect bites and stings and for some food allergies. Loratadine is much less likely to make you feel sleepy than some other antihistamines such as diphenhydramine. Most people prefer to take a non-drowsy antihistamine instead of a sedating one. An exception is when you want the medicine to make you sleepy because you’ve got itchy skin that’s keeping you awake.

Loratadine is a histamine [H1] receptor blocker, it works by blocking the action of histamine, a substance in the body that causes allergic symptoms. When you come into contact with something you have an allergy to, such as pollen, animal hair or fur, house dust or insect bites, your body produces a chemical called histamine. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Usually histamine is a useful substance but in an allergic reaction it causes unpleasant symptoms including itchy, watery eyes, running or blocked nose, sneezing and skin rashes. Loratadine blocks the effects of histamine and so reduces these symptoms.

Loratadine is also available in combination with pseudoephedrine (Sudafed, others). This article only includes information about the use of loratadine alone. If you are taking the loratadine and pseudoephedrine combination product, read the information on the package label or ask your doctor or pharmacist for more information.

Loratadine is available on prescription. You can also buy loratadine from pharmacies and supermarkets.

Loratadine comes as a syrup (liquid), an immediate acting and extended release tablet, and a rapidly disintegrating (dissolving) tablet to take by mouth. It is usually taken once a day with or without food. Follow the directions on the package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take loratadine exactly as directed. Do not take more or less of it or take it more often than directed on the package label or recommended by your doctor. If you take more loratadine than directed, you may experience drowsiness.

If you are taking the rapidly disintegrating tablet, follow the package directions to remove the tablet from the blister package without breaking the tablet. Do not try to push the tablet through the foil. After you remove the tablet from the blister package, immediately place it on your tongue and close your mouth. The tablet will quickly dissolve and can be swallowed with or without water.

Do not use loratadine to treat hives that are bruised or blistered, that are an unusual color, or that do not itch. Call your doctor if you have this type of hives.

Stop taking loratadine and call your doctor if your hives do not improve during the first 3 days of your treatment or if your hives last longer than 6 weeks. If you do not know the cause of your hives, call your doctor.

If you are taking loratadine to treat hives, and you develop any of the following symptoms, get emergency medical help right away:

• difficulty swallowing,
• speaking, or breathing;
• swelling in and around the mouth or swelling of the tongue;
• wheezing; drooling;
• dizziness; or loss of consciousness.

These may be symptoms of a life-threatening allergic reaction called anaphylaxis. If your doctor suspects that you may experience anaphylaxis with your hives, he may prescribe an epinephrine injector (EpiPen). Do not use loratadine in place of the epinephrine injector.

Do not use this medication if the safety seal is open or torn.

Loratadine was evaluated for efficacy and safety in 228 patients with perennial allergic rhinitis. Taken at a dose of 10 mg once daily, loratadine was significantly more effective than placebo and comparable to terfenadine, 60 mg taken twice daily, in reducing combined symptom scores in this patient population. Efficacy was maintained throughout the 28 day course of treatment ¹⁰. The overall incidence of side effects with loratadine was low (14%) with few occurrences of sedation (3%) and dry mouth (4%).

Key facts

• It’s usual to take loratadine once a day.
• Loratadine is classed as a non-drowsy antihistamine, but some people still find it makes them feel slightly sleepy.
• Children may also have a headache and feel tired or nervous after taking loratadine.
• It’s best NOT to drink alcohol while you’re taking loratadine as it can make you feel sleepy.
• Loratadine is also called by the brand names Clarityn Allergy, Clarityn Rapide Allergy, Alavert, Claritin, Claritin Reditab, Clear-Atadine, Dimetapp ND, ohm Allergy Relief, QlearQuil All Day & Night, Tavist ND, Wal-itin.

Before taking loratadine – Precautions

• tell your doctor and pharmacist if you are allergic to loratadine, any other medications, or any of the ingredients in the type of loratadine you will be taking. Check the package label for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention medications for colds and allergies.
• tell your doctor if you have or have ever had asthma or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking loratadine, call your doctor.
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of the orally disintegrating tablets may contain aspartame that forms phenylalanine.

What is fexofenadine used for

Fexofenadine is used to relieve the allergy symptoms of seasonal allergic rhinitis (”hay fever”), including runny nose; sneezing; red, itchy, or watery eyes (allergic conjunctivitis); itching of the nose, throat, or roof of the mouth in adults and children 2 years of age and older. Fexofenadine is also used to relieve symptoms of urticaria (hives; red, itchy raised areas of the skin), eczema including itching and rash in adults and children 6 months of age and older.

Fexofenadine is also used for reactions to insect bites, stings, some food allergies and a condition called chronic idiopathic urticaria in adults and children.

Fexofenadine is known as a non-drowsy antihistamine. It’s less likely to make you feel sleepy than some other antihistamines.

Fexofenadine dose

Usual Adult Dose for Allergic Rhinitis

180 mg orally once a day OR 60 mg orally 2 times a day

Maximum dose: 180 mg/day

Comment:

• Tablets should be taken with water.

Uses:

• Relief of symptoms associated with seasonal allergic rhinitis (e.g., runny nose, sneezing, itchy, watery eyes, itching of the nose/throat)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Usual Adult Dose for Urticaria

180 mg orally once a day OR 60 mg orally 2 times a day

Maximum dose: 180 mg/day

Comment:

• Tablets should be taken with water.

Uses:

• Relief of symptoms associated with seasonal allergic rhinitis (e.g., runny nose, sneezing, itchy, watery eyes, itching of the nose/throat)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Usual Pediatric Dose for Allergic Rhinitis

6 months to 2 years: 15 mg orally 2 times a day

2 years to 11 years: 30 mg orally 2 times a day

12 years and older: 180 mg orally once a day OR 60 mg orally 2 times a day

Comments:

• The oral suspension may be used by patients 6 months and older.
• Tablets and oral dissolving tablets may be used by patients 6 to 11 years of age.
• Gel-coated tablet formulations should be limited to patients 12 years and older.

Uses:

• Relief of symptoms associated with seasonal allergic rhinitis (e.g., runny nose, sneezing, itchy, watery eyes, itching of the nose/throat)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Usual Pediatric Dose for Urticaria

6 months to 2 years: 15 mg orally 2 times a day

2 years to 11 years: 30 mg orally 2 times a day

12 years and older: 180 mg orally once a day OR 60 mg orally 2 times a day

Comments:

• The oral suspension may be used by patients 6 months and older.
• Tablets and oral dissolving tablets may be used by patients 6 to 11 years of age.
• Gel-coated tablet formulations should be limited to patients 12 years and older.

Uses:

• Relief of symptoms associated with seasonal allergic rhinitis (e.g., runny nose, sneezing, itchy, watery eyes, itching of the nose/throat)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Renal Dose Adjustments

Adult:

• Creatinine Clearance 90 mL/min or less: 60 mg orally once a day

Pediatric:

6 months to less than 2 years:

• Creatinine Clearance 90 mL/min or less: 15 mg orally once a day

2 to 11 years:

• Creatinine Clearance 90 mL/min or less: 30 mg orally once a day

Liver Dose Adjustments

Data not available

Dialysis

Data not available

How and when to take fexofenadine

If you or your child have been prescribed fexofenadine, follow your doctor’s instructions about how and when to take it.

How should fexofenadine be used?

Fexofenadine comes as a tablet and a suspension (liquid) to take by mouth. It is usually taken with water once or twice a day. Fexofenadine will work better if it is not taken with fruit juices such as orange, grapefruit, or apple juice. Take fexofenadine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take fexofenadine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Fexofenadine controls the symptoms of seasonal allergic rhinitis and urticaria but does not cure these conditions. Continue to take fexofenadine even if you feel well and are not experiencing these symptoms. If you wait too long between doses, your symptoms may become worse.

Shake the suspension well before each use to mix the medication evenly.

How much should I take?

Fexofenadine comes as tablets (30mg, 120mg and 180mg).

How much you take depends on why you’re taking fexofenadine:

• For hay fever – the usual dose for adults and children aged 12 years and over is 120mg once a day. The usual dose for children aged 6 to 11 years is 30mg twice a day. In this case, try to space the doses 10 to 12 hours apart.
• For hives (nettle rash) – the usual dose for adults and children aged 12 years and over is 180mg once a day.

Fexofenadine Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For symptoms of hay fever:

• For oral dosage form (capsules, tablets):
  • Adults and children 12 years of age and older—60 milligrams (mg) two times a day, or 180 mg once a day.
  • Children 6 to 11 years of age—30 mg two times a day.
  • Children 4 to 6 years of age—Use and dose must be determined by your doctor .
  • Children and infants up to 4 years of age—Use is not recommended.
• For oral dosage form (disintegrating tablets):
  • Children 6 to 11 years of age—30 milligrams (mg) two times a day, on an empty stomach.
  • Children 4 to 6 years of age—Use and dose must be determined by your doctor .
  • Children and infants up to 4 years of age—Use is not recommended.
• For oral dosage form (suspension):
  • Children 4 to 11 years of age—30 milligrams (mg) or 5 milliliters (mL) two times a day.
  • Children younger than 4 years of age—Use and dose must be determined by your doctor.

For symptoms of chronic hives:

• For oral dosage form (capsules, tablets):
  • Adults and children 12 years of age and older—60 milligrams (mg) two times a day, or 180 mg once a day.
  • Children 4 to 11 years of age—30 mg two times a day.
  • Children younger than 4 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (disintegrating tablets):
  • Children 4 to 11 years of age—30 milligrams (mg) two times a day, on an empty stomach.
  • Children younger than 4 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (suspension):
  • Children 4 to 11 years of age—30 milligrams (mg) or 5 milliliters (mL) two times a day.
  • Children 6 months to 4 years of age—15 mg or 2.5 mL two times a day.
  • Children younger than 6 months of age—Use and dose must be determined by your doctor.

How to take fexofenadine

• If you’re taking 30mg fexofenadine tablets, you can take them with or without food.
• If you’re taking 120mg and 180mg fexofenadine tablets, take them before a meal.

Always take your fexofenadine tablets with a drink of water. Swallow them whole – do not chew them.

Do NOT take fexofenadine with juice such as grapefruit, orange, or apple juice.

You should NOT take antacids that contain aluminum or magnesium hydroxide within 15 minutes of taking this medicine. If you are uncertain about this, ask your doctor or pharmacist .

For patients using the oral disintegrating tablet form of fexofenadine:

• Make sure your hands are dry.
• Do not push the tablet through the foil backing of the package. Instead, gently peel back the foil backing and remove the tablet.
• Immediately place the tablet on top of the tongue. Do not chew or break the tablet.
• The tablet will dissolve in seconds, and you may swallow it with your saliva. You may drink a glass of water after the tablet has dissolved.
• Always take this tablet on an empty stomach.

Shake the oral liquid well before using it. Measure the liquid with a marked measuring spoon, oral syringe, or medicine cup.

When to take fexofenadine

You may only need to take fexofenadine on a day you have symptoms, such as if you’ve been exposed to something you’re allergic to like animal hair. Or you may need to take it regularly to prevent symptoms, such as to stop hay fever during spring and summer.

What if I forget to take it?

If you’re taking fexofenadine once a day, do not take a double dose to make up for a forgotten dose. Take the next dose at the usual time as prescribed by your doctor.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much fexofenadine?

Fexofenadine is generally very safe. Taking too much is unlikely to harm you.

If you take an extra dose by mistake, you might get some of the common side effects. If this happens or you’re concerned, contact your doctor.

Fexofenadine side effects

Like all medicines, fexofenadine can cause side effects, although not everyone gets them.

Common side effects

Common side effects of fexofenadine happen in more than 1 in 100 people. Talk to your doctor or pharmacist if these side effects bother you or don’t go away:

• feeling sick
• vomiting
• feeling sleepy
• headache
• dry mouth
• feeling dizzy

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them.

Gastrointestinal

• Very common (10% or more): Vomiting (up to 12%)
• Common (1% to 10%): Nausea, diarrhea, stomach discomfort

Nervous system

• Very common (10% or more): Headache (up to 10.3%)
• Common (1% to 10%): Drowsiness, dizziness, somnolence

Other side effects

• Common (1% to 10%): Otitis media, pyrexia, fatigue, extremity pain

Respiratory

• Common (1% to 10%): Cough, upper respiratory tract infection, rhinorrhea
• Frequency not reported: Dyspnea

Musculoskeletal

• Common (1% to 10%): Back pain

Genitourinary

• Common (1% to 10%): Dysmenorrhea

Psychiatric

• Frequency not reported: Insomnia, nervousness, nightmares, sleep disorders or paroniria/excessive dreaming

Cardiovascular

• Frequency not reported: Palpitations, tachycardia, chest tightness

Hypersensitivity

• Frequency not reported: Hypersensitivity reactions, angioedema, systemic anaphylaxis

Dermatologic

• Frequency not reported: Rash, pruritus, flushing

Less common side effects

• back pain
• body aches or pain
• chills
• coughing
• diarrhea
• difficulty with moving
• dizziness
• ear congestion
• earache
• fever
• headache
• joint pain
• loss of voice
• muscle aching or cramping
• muscle pains or stiffness
• nasal congestion
• nausea
• pain in arms or legs
• pain or tenderness around eyes or cheekbones
• painful menstrual bleeding
• redness or swelling in ear
• ringing or buzzing in ears
• runny or stuffy nose
• sleepiness or unusual drowsiness
• sneezing
• sore throat
• stomach upset
• swollen joints
• unusual feeling of tiredness or weakness
• viral infection (such as cold and flu)

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Rare side effects

• Nervousness
• Rash
• Sleeplessness
• Terrifying dreams
• Trouble sleeping
• Chest tightness
• Feeling of warmth, redness of the face, neck, arms and occasionally, upper chest
• Large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• Shortness of breath, difficult or labored breathing

Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if you have any of the side effects listed above.

Serious side effects

It’s rare to have a serious side effect with fexofenadine.

• Tell your doctor straight away if you have a fast or irregular heartbeat.

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction to fexofenadine.

• A serious allergic reaction is an emergency. Contact a doctor straight away if you think you or someone around you is having a serious allergic reaction.

The warning signs of a serious allergic reaction are:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• wheezing
• tightness in the chest or throat
• having trouble breathing or talking
• swelling of the mouth, face, lips, tongue, or throat

These are not all the side effects of fexofenadine. For a full list see the leaflet inside your medicines packet.

How to cope with side effects

What to do about:

• feeling sick – stick to simple meals and don’t eat rich or spicy food
• feeling sleepy – try a different non-drowsy antihistamine. If this doesn’t help, talk to your doctor
• headache – take an everyday painkiller like paracetamol or ibuprofen
• dry mouth – chew sugar-free gum or suck sugar-free sweets
• feeling dizzy – lie down until the dizziness passes, then get up slowly. Move slowly and carefully. Avoid coffee, cigarettes, alcohol and recreational drugs. If the dizziness doesn’t get better within a couple of days, speak to your pharmacist or doctor.

Human Toxicity Reports

Safety and efficacy of fexofenadine hydrochloride have not been established in children younger than 6 years of age ⁶.

In clinical trials, dysmenorrhea occurred in 1.5% of patients receivingoral fexofenadine 60 mg twice daily, compared to 0.3% in patients receiving placebo ¹¹.

In controlled clinical studies in patients 12 years of age and older with allergic rhinitis receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily or placebo, drowsiness or fatigue occurred in 1.3% of patients, compared with 0.9% of those receiving placebo ¹². In these studies in patients receiving fexofenadine hydrochloride dosages of 180 mg once daily (as conventional tablets) or placebo, headache was reported in 10.6 or 7.5% of patients, respectively. In controlled studies in children 6-11 years of age with seasonal allergic rhinitis receiving fexofenadine hydrochloride dosages of 30 mg twice daily or placebo, headache was reported in 7.2 or 6.6% of patients, respectively, while pain was reported in 2.4 or 0.4% of patients, respectively ¹².

During controlled clinical studies, nausea and dyspepsia were reported in 1.6 and 1.3%, respectively, of patients receiving oral fexofenadine hydrochloride dosages of 60 mg twice daily versus 1.5 and 0.6%, respectively, of those receiving placebo ¹².

Rash, urticaria, pruritus, and hypersensitivity reactions including angioedema, chest tightness, dyspnea, flushing, or anaphylaxis have been reported rarely in patients receiving fexofenadine hydrochloride ⁶.

In controlled studies in adults and children 12 years and older with chronic idiopathic urticaria receiving fexofenadine hydrochloride dosages of 60 mg twice daily or placebo, both back pain and sinusitis were reported in 2.2 or 1.1% of patients, respectively ⁶.

Clinical data from over 2000 patients indicate that fexofenadine hydrochloride lacks the cardiotoxic potential of its parent drug terfenadine ¹². In 714 patients with seasonal allergic rhinitis, fexofenadine hydrochloride dosages of 60-240 mg twice daily were not associated with statistically significant mean increases in the QT interval corrected for rate (QTc) in controlled clinical studies. In addition, in 231 healthy individuals, fexofenadine hydrochloride dosages of 240 mg given once daily for 1 year also were not associated with statistically significant increases in the mean QTc. Even at dosages exceeding these (e.g., up to 400 mg twice daily for 6 days in 40 patients, up to 690 mg twice daily for about 1 month in 32 patients, up to 800 mg given in a single dose in 87 patients), statistically significant mean increases in the QTc or other ECG abnormalities have not been reported in healthy adults or patients with seasonal allergic rhinitis ¹².

Viral infection (eg, cold, influenza) or dysmenorrhea was reported in 2.5 or 1.5% of patients 12 years of age and older receiving fexofenadine hydrochloride in dosages of 60 mg twice daily, respectively. In controlled clinical studies in adults and children 12 years of age and older receiving fexofenadine hydrochloride dosages of 180 mg once daily or placebo, upper respiratory tract infection was reported in 3.2 or 3.1% of patients, respectively, while back pain was reported in 2.8 or 1.4% of patients, respectively ⁶.

In controlled studies in children 6-11 years of age with seasonal allergic rhinitis receiving fexofenadine hydrochloride 30 mg twice daily, upper respiratory tract infection, coughing, accidental injury, fever, and otitis media occurred in 4.3, 3.8, 2.9, 2.4, and 2.4% of children, respectively, while these adverse effects were reported in 1.7, 1.3, 1.3, 0.9, and 0%, respectively, in those receiving placebo ⁶.

To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration’s Spontaneous Reporting System database were examined ¹³. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity. Spontaneous reports from the general medical community. As of April 1, 1992, 25 cases of torsades de pointes had been reported to the Food and Drug Administration’s Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug Terfenadine, but not its metabolite Fexofenadine, may have actions similar those of quinidine that are responsible for inducing arrhythmia ¹³. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect. Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidine-like action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction ¹³. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, the authors conclude that fexofenadine HCl has no significant effect on QTc, even at doses > 10-fold higher than that is efficacious for seasonal allergic rhinitis ¹⁴.

Fexofenadine overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Little information is available regarding toxicity. Clinical effects are anticipated to be an extension of adverse effects reported with therapeutic use. Dizziness, drowsiness, and dry mouth have been reported with fexofenadine overdose.

Symptoms of Allegra overdose may include:

• dizziness
• drowsiness
• dry mouth

References

1. Gilboa SM, et al. 2009. National Birth Defects Prevention Study: Use of antihistamine medications during early pregnancy and isolated major malformations. Birth Defects Res A Clin Mol Teratol 85(2):137-150.
2. Diav-Citrin O, et al. 2003. Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study. J Allergy Clin Immunol 111(6):1239-1243.
3. Kallen B. 2002. Use of antihistamine drugs in early pregnancy and delivery outcome. J Matern Fetal Neonatal Med 11:146-152.
4. Schatz M, Petitti D. 1997. Antihistamines and pregnancy. Ann Allergy Asthma Immunol 78:157-159.
5. Loebstein R, et al. 2000. Pregnancy outcome after gestational exposure to terfenadine: A multicenter, prospective controlled study. Immunology and Allergy Clinics of North America 20(4):807-30.
6. McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34
7. Lucas BD Jr, et al: 1995. Terfenadine pharmacokinetics in breast milk in lactating women. Clin Pharmacol Ther. Apr;57(4):398-402.
8. Ito S, et al. 1993. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 168:1393-9.
9. Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug-binding site. Molecular immunology. 2016;71:143-151. doi:10.1016/j.molimm.2016.02.003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800003/
10. Bruttmann G, et al; J Allergy Clin Immunol 83 (2 Pt 1): 411-16; 1989 https://www.ncbi.nlm.nih.gov/pubmed/2563743
11. Physicians Desk Reference 60th ed, Thomson PDR, Montvale, NJ 2006., p. 2859
12. McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 33
13. Woosley RL et al; JAMA 269 (12): 1532-6, 1993 https://jamanetwork.com/journals/jama/article-abstract/404647
14. Pratt CM et al; Am J Cardiol 83 (10): 1451-4; 1999 https://www.ncbi.nlm.nih.gov/pubmed/10335761

What is gardasil

Gardasil (HPV quadrivalent vaccine) and Gardasil 9 (HPV 9-valent vaccine) are used in both females and males. Another form of HPV vaccine (Cervarix – a  bivalent HPV vaccine) is used only in females.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Human papillomavirus (HPV) can cause genital warts, cancer of the cervix, anal cancer, and various cancers of the vulva or vagina; cancers of the penis in men; and cancers of the anus and back of the throat, including the base of the tongue and tonsils (oropharynx), in both women and men. Some health effects caused by HPV can be prevented by the HPV vaccines like Gardasil.

Nearly 80 million people—about one in four—are currently infected with HPV in the United States. About 14 million people, including teens, become infected with HPV each year.

Over 30,000 people in the United States each year are affected by a cancer caused by HPV infection. While there is screening available for cervical cancer for women, there is no screening for the other cancers caused by HPV infection, like cancers of the mouth/throat, anus/rectum, penis, vagina, or vulva.

Cervical cancer remains the most common cancer in Eastern and Central Africa with an estimated with estimated age standardized rates of 42.7 and 30.6 respectively compared with 2–5 in Western Europe and Australia ¹. Mortality is highest in Eastern Africa at 27 per 10,000 compared to less than 2 per 100,000 in Western Asia/Europe, Australia and New Zealand ². Cervical cancer is the 4th commonest cancer affecting women worldwide with over 260,000 deaths reported in 2012 ².

HPV vaccination provides safe, effective, and lasting protection against the HPV infections that most commonly cause cancer and is supplemented by cervical cancer screening later in life. This is because HPV vaccines do not protect against all high-risk and potential high-risk HPV types.

The quadrivalent (Gardasil 4) HPV vaccine protecting against human papilloma virus (HPV) types 16/18/6/11 and the bivalent (Cervirax) vaccine protecting against infection with HPV-16/18 were both originally used as a three dose schedule. A third vaccine, the nonavalent HPV (Gardasil 9) vaccine protecting against HPV types 6/11/16/18/31/33/45/52/58 was approved by Food and Drug Administration (FDA) in 2014 ³.

Three HPV vaccines have been licensed by the U.S. Food and Drug Administration (FDA):

• Gardasil (Merck) is a quadrivalent HPV vaccine (4vHPV) that protects against HPV types 6, 11, 16, and 18.
• Gardasil-9 (Merck) is a nine-valent HPV vaccine (9vHPV) that protects against HPV types 6, 11, 16, 18, 31, 45, 52, and 58.
• Cervirax is a bivalent HPV vaccine (2vHPV) that protects against HPV types 16 and 18

All three HPV vaccines protect against the two HPV types, 16 and 18, that cause most HPV cancers.

Gardasil is used in girls and young women ages 9 through 26 to prevent cervical/vaginal/anal cancers caused by certain types of HPV.

Gardasil is also used in boys and young men ages 9 through 26 to prevent anal cancer or genital warts caused by certain types of HPV.

You may receive Gardasil even if you have already had genital warts, or had a positive HPV test or abnormal pap smear in the past. However, Gardasil vaccine will not treat active genital warts or HPV-related cancers, and it will not cure HPV infection.

Gardasil only prevents diseases caused by HPV types 6, 11, 16, and 18. It will not prevent diseases caused by other types of HPV.

The Centers for Disease Control and Prevention (CDC) recommends HPV vaccine for all boys and girls ages 11 or 12 years old. The vaccine is also recommended in teenage boys and girls who have not already received the vaccine or have not completed all booster shots.

Like any vaccine, the Gardasil and Gardasil 9 may not provide protection from disease in every person.

Some people should NOT get Gardasil and Gardasil 9 vaccine

• Anyone who has had a severe (life-threatening) allergic reaction to a dose of HPV vaccine should not get another dose.
• Anyone who has a severe (life threatening) allergy to any component of HPV vaccine should not get the vaccine.
• Tell your doctor if you have any severe allergies that you know of, including a severe allergy to yeast.
• HPV vaccine is not recommended for pregnant women. If you learn that you were pregnant when you were vaccinated, there is no reason to expect any problems for you or your baby. Any woman who learns she was pregnant when she got HPV vaccine is encouraged to contact the manufacturer’s registry for HPV vaccination during pregnancy. Women who are breastfeeding may be vaccinated.
• If you have a mild illness, such as a cold, you can probably get the vaccine today. If you are moderately or severely ill, you should probably wait until you recover. Your doctor can advise you.

What kinds of problems does HPV infection cause?

Most people with HPV never develop symptoms or health problems. Most HPV infections (9 out of 10) go away by themselves within two years. But, sometimes, HPV infections will last longer, and can cause certain cancers and other diseases. HPV infections can cause:

• cancers of the cervix, vagina, and vulva in women;
• cancers of the penis in men; and
• cancers of the anus and back of the throat, including the base of the tongue and tonsils (oropharynx), in both women and men.

Every year in the United States, HPV causes 32,500 cancers in men and women.

Why does my child need HPV vaccine?

HPV vaccine is important because it protects against cancers caused by human papillomavirus (HPV) infection. HPV is a very common virus; nearly 80 million people—about one in four—are currently infected in the United States. About 14 million people, including teens, become infected with HPV each year.

Most people with HPV never develop symptoms or health problems. Most HPV infections (9 out of 10) go away by themselves within two years. But, sometimes, HPV infections will last longer, and can cause certain cancers and other diseases. HPV infection can cause:

• cancers of the cervix, vagina, and vulva in women;
• cancers of the penis in men; and
• cancers of the anus and back of the throat, including the base of the tongue and tonsils (oropharynx), in both women and men.

Every year in the United States, HPV causes 32,500 cancers in men and women. HPV vaccination can prevent most of the cancers (about 30,000) from ever developing.

How do people get an HPV infection?

People get HPV from another person during intimate sexual contact. Most of the time, people get HPV from having vaginal and/or anal sex. Men and women can also get HPV from having oral sex or other sex play. A person can get HPV even if their partner doesn’t have any signs or symptoms of HPV infection. A person can have HPV even if years have passed since he or she had sexual contact with an infected person. Most people do not realize they are infected. They also don’t know that they may be passing HPV to their sex partner(s). It is possible for someone to get more than one type of HPV.

It’s not very common, but sometimes a pregnant woman with HPV can pass it to her baby during delivery. The child might develop recurrent respiratory papillomatosis, a rare but dangerous condition where warts caused by HPV (similar to genital warts) grow inside the throat.

There haven’t been any documented cases of people getting HPV from surfaces in the environment, such as toilet seats. However, someone could be exposed to HPV from objects (toys) shared during sexual activity if the object has been used by an infected person.

How common is HPV and the health problems caused by HPV?

HPV (the virus): About 79 million Americans are currently infected with HPV. About 14 million people become newly infected each year. HPV is so common that almost every person who is sexually-active will get HPV at some time in their life if they don’t get the HPV vaccine.

Health problems related to HPV include genital warts and cervical cancer.

Genital warts: Before HPV vaccines were introduced, roughly 340,000 to 360,000 women and men were affected by genital warts caused by HPV every year.* Also, about one in 100 sexually active adults in the U.S. has genital warts at any given time.

Cervical cancer: Every year, nearly 12,000 women living in the U.S. will be diagnosed with cervical cancer, and more than 4,000 women die from cervical cancer—even with screening and treatment.

There are other conditions and cancers caused by HPV that occur in people living in the United States. Every year, approximately 19,400 women and 12,100 men are affected by cancers caused by HPV.

*These figures only look at the number of people who sought care for genital warts. This could be an underestimate of the actual number of people who get genital warts.

How do I know if I have HPV?

There is no test to find out a person’s “HPV status.” Also, there is no approved HPV test to find HPV in the mouth or throat.

There are HPV tests that can be used to screen for cervical cancer. These tests are only recommended for screening in women aged 30 years and older. HPV tests are not recommended to screen men, adolescents, or women under the age of 30 years.

Most people with HPV do not know they are infected and never develop symptoms or health problems from it. Some people find out they have HPV when they get genital warts. Women may find out they have HPV when they get an abnormal Pap test result (during cervical cancer screening). Others may only find out once they’ve developed more serious problems from HPV, such as cancers.

How can I avoid HPV and the health problems it can cause?

You can do several things to lower your chances of getting HPV.

Get vaccinated. The HPV vaccine is safe and effective. It can protect against diseases (including cancers) caused by HPV when given in the recommended age groups. CDC recommends 11 to 12 year olds get two doses of HPV vaccine to protect against cancers caused by HPV ⁴.

Get screened for cervical cancer. Routine screening for women aged 21 to 65 years old can prevent cervical cancer.

If you are sexually active:

• Use latex condoms the right way every time you have sex. This can lower your chances of getting HPV. But HPV can infect areas not covered by a condom – so condoms may not fully protect against getting HPV;
• Be in a mutually monogamous relationship – or have sex only with someone who only has sex with you.

Who should get HPV vaccine?

All girls and boys who are 11 or 12 years old should get the recommended series of Gardasil vaccine. The vaccination series can be started at age 9 years. Teen boys and girls who did not get vaccinated when they were younger should get it now. Gardasil vaccine is recommended for young women through age 26, and young men through age 21. Gardasil vaccine is also recommended for the following people, if they did not get vaccinated when they were younger:

• young men who have sex with men, including young men who identify as gay or bisexual or who intend to have sex with men through age 26;
• young adults who are transgender through age 26; and
• young adults with certain immunocompromising conditions (including HIV) through age 26.

Who else should get the HPV vaccine?

Teen boys and girls who did not start or finish the HPV vaccine series when they were younger should get it now.

HPV vaccine is recommended for young women through age 26, and young men through age 21. HPV vaccine is also recommended for the following people, if they did not get vaccinated when they were younger:

• young men who have sex with men, including young men who identify as gay or bisexual or who intend to have sex with men through age 26;
• young adults who are transgender through age 26; and
• young adults with certain immunocompromising conditions (including HIV) through age 26.

When should my child be vaccinated?

In this video, a family physician explains his decision, as a doctor and a parent, to make sure each of his children received HPV vaccine at age 11 or 12. HPV vaccine is cancer prevention. Ask about it for your child.

All kids who are 11 or 12 years old should get two shots of HPV vaccine six to twelve months apart. Adolescents who receive their two shots less than five months apart will require a third dose of HPV vaccine.

If your teen hasn’t gotten the vaccine yet, talk to their doctor or nurse about getting it for them as soon as possible. If your child is older than 14 years, three shots will need to be given over 6 months. Also, three doses are still recommended for people with certain immunocompromising conditions aged 9 through 26 years.

How well does HPV vaccine work?

Gardasil HPV vaccines work extremely well. Clinical trials showed HPV vaccines provide close to 100% protection against cervical precancers and genital warts. Since the first HPV vaccine was recommended in 2006, there has been a 64% reduction in vaccine-type HPV infections among teen girls in the United States. Studies have shown that fewer teens are getting genital warts and cervical precancers are decreasing. In other countries, such as Australia, where HPV vaccination coverage is higher than in the United States, large decreases have been observed in these HPV-associated outcomes. HPV vaccines offer long-lasting protection against HPV infection and HPV disease. There has been no evidence to suggest that HPV vaccine loses any ability to provide protection over time. Data are available for about 10 years of follow-up after vaccination.

Like all vaccines, HPV vaccine is monitored on an ongoing basis to make sure it remains safe and effective. If it turns out that protection from HPV vaccine is not long-lasting, then the Advisory Committee on Immunization Practices would review the data and determine whether a booster dose would be recommended.

Even if it has been months or years since the last shot, the HPV vaccine series should be completed—but they do not need to restart the series.

HPV vaccine is recommended based on age, not sexual experience. Even if someone has already had sex, they should still get HPV vaccine. Even though a person’s first HPV infection usually happens during one of the first few sexual experiences, a person might not be exposed to all of the HPV types that are covered by HPV vaccines.

Does HPV vaccination offer similar protection from cervical cancer in all racial/ethnic groups?

Yes. Several different HPV types cause cervical cancer. HPV vaccines are designed to prevent the HPV types that cause most cervical cancers, so HPV vaccination will provide high protection for all racial/ethnic groups.

All three licensed HPV vaccines protect against types 16 and 18, which cause the majority of cervical cancers across racial/ethnic groups (67% of the cervical cancers among whites, 68% among blacks, and 64% among Hispanics). The 9-valent Gardasil vaccine protects against seven HPV types that cause about 80% of cervical cancer among all racial/ethnic groups in the United States.

Teens and young adults who haven’t completed the HPV vaccine series should make an appointment today to get vaccinated. To protect against cervical cancer, women age 21–65 years should get screened for cervical cancer at regular intervals and get follow-up care as recommended by their doctor or nurse.

Where can I find HPV Vaccines?

HPV vaccine may be available at private doctor offices, community health clinics, school-based health centers, and health departments.

If your doctor does not stock HPV vaccine, ask for a referral. If you don’t have a regular source of health care, federally funded health centers can provide services. Locate one near you here (https://www.vaccines.gov/getting/where/index.html).

How can someone get help paying for HPV vaccine?

The Vaccines for Children program helps families of eligible children who might not otherwise have access to vaccines. The program provides vaccines at no cost to children ages 18 years and younger who are uninsured, Medicaid-eligible, or American Indian/Alaska Native.

Children through 18 years of age who meet at least one of the following criteria are eligible to receive Vaccines for Children program vaccine:

• Medicaid eligible: A child who is eligible for the Medicaid program. (For the purposes of the VFC program, the terms “Medicaid-eligible” and “Medicaid-enrolled” are equivalent and refer to children who have health insurance covered by a state Medicaid program)
• Uninsured: A child who has no health insurance coverage
• American Indian or Alaska Native: As defined by the Indian Health Care Improvement Act (25 U.S.C. 1603)
• Underinsured: Underinsured means the child has health insurance, but it:
  • Doesn’t cover vaccines, or
  • Doesn’t cover certain vaccines, or
  • Covers vaccines but has a fixed dollar limit or cap for vaccines. Once that fixed dollar amount is reached, a child is then eligible.
  • Underinsured children are eligible to receive vaccines only at Federally Qualified Health Centers (FQHC) or Rural Health Clinics (RHC). An Federally Qualified Health Center is a type of provider that meets certain criteria under Medicare and Medicaid programs. To locate an Federally Qualified Health Center or Rural Health Clinic, contact the state Vaccines for Children program coordinator (https://www.cdc.gov/vaccines/imz-managers/awardee-imz-websites.html).

Children whose health insurance covers the cost of vaccinations are not eligible for Vaccines for Children program vaccines, even when a claim for the cost of the vaccine and its administration would be denied for payment by the insurance carrier because the plan’s deductible had not been met.

Gardasil Vaccine Recommendations

• The Centers for Disease Control and Prevention (CDC) recommends Gardasil HPV vaccine for girls and boys at ages 11 or 12 years to protect against cancers caused by HPV infections. (Vaccination can be started at age 9.)
• The Advisory Committee on Immunization Practices (ACIP) also recommends Gardasil vaccination for females aged 13 through 26 years and males aged 13 through 21 years who are not adequately vaccinated previously.
• Gardasil vaccination is also recommended through age 26 years for gay, bisexual, and other men who have sex with men, transgender people, and for immunocompromised persons (including those with HIV infection) not adequately vaccinated previously.

Ideally, adolescents should be vaccinated before they are exposed to HPV. However, people who have already been infected with one or more HPV types can still get protection from other HPV types in the Gardasil vaccine.

Why is HPV vaccine recommended at age 11 or 12 years?

For HPV vaccine to be most effective, the HPV vaccine series should be given prior to exposure to HPV. There is no reason to wait to vaccinate until teens reach puberty or start having sex. Preteens should receive all recommended doses of the HPV vaccine series long before they begin any type of sexual activity.

Why is HPV vaccine not mandatory for school entry?

Each state determines which vaccines are required for school entry. Many factors are taken into consideration before requiring any vaccine for school entry, including: community support for the requirement, financial resources needed to implement the requirement, burden on school personnel for enforcing the requirement, vaccine supply, and current vaccination coverage levels.

Since almost every state requires Tdap (tetanus, diphtheria, and acellular pertussis vaccine) for middle school entry, parents can use this visit to the doctor to get the first HPV and quadrivalent meningococcal conjugate vaccines for their preteen at the same time.

Is Gardasil safe?

Gardasil HPV vaccines are very safe. Scientific research shows the benefits of Gardasil vaccination far outweigh the potential risks. Like all medical interventions, vaccines can have some side effects.

All vaccines used in the United States, including Gardasil vaccines, are required to go through years of extensive safety testing before they are licensed by the U.S. Food and Drug Administration (FDA). During clinical trials conducted before they were licensed:

• 9-valent Gardasil vaccine was studied in more than 15,000 males and females
• Quadrivalent Gardasil vaccine was studied in more than 29,000 males and females
• Bivalent Cervarix HPV vaccine was studied in more than 30,000 females
• Each HPV vaccine was found to be safe and effective.

How do you know that the HPV vaccine is safe?

The United States currently has the safest, most effective vaccine supply in history. Years of testing are required by law to ensure the safety of vaccines before they are made available for use in the United States. This process can take ten years or longer. Once a vaccine is in use, CDC and the Food and Drug Administration (FDA) monitor any associated side effects or possible side effects (adverse events) through the Vaccine Adverse Event Reporting System and other vaccine safety systems.

All three HPV vaccines—Cervarix®, Gardasil®, and Gardasil® 9—went through years of extensive safety testing before they were licensed by FDA. Cervarix® was studied in clinical trials with more than 30,000 females. Gardasil® trials included more than 29,000 females and males, and Gardasil® 9 trials included more than 15,000 females and males. No serious safety concerns were identified in these clinical trials. FDA only licenses a vaccine if it is safe, effective, and the benefits outweigh the risks. CDC and FDA continue to monitor HPV vaccines to make sure they are safe and beneficial for the public.

Gardasil vaccine schedule

Two doses of Gardasil vaccine are recommended for most persons starting the series before their 15th birthday.

• The second dose of Gardasil vaccine should be given 6 to 12 months after the first dose.
• Adolescents who receive 2 doses less than 5 months apart will require a third dose of Gardasil vaccine.

Three doses of Gardasil vaccine are recommended for teens and young adults who start the series at ages 15 through 26 years, and for immunocompromised persons.

• The recommended 3-dose schedule is 0, 1–2 and 6 months.
• Three doses are recommended for immunocompromised persons (including those with HIV infection) aged 9–26 years.

Why are two doses of Gardasil vaccine recommended for 9–14 year olds, while older adolescents need three doses?

Since 2006, HPV vaccines have been recommended in a three-dose series given over six months. In 2016, CDC changed the recommendation to two doses for persons starting the series before their 15th birthday. The second dose of HPV vaccine should be given six to twelve months after the first dose. Adolescents who receive their two doses less than five months apart will require a third dose of HPV vaccine.

Teens and young adults who start the series at ages 15 through 26 years still need three doses of HPV vaccine Also, three doses are still recommended for people with certain immunocompromising conditions aged 9 through 26 years.

CDC makes recommendations based on the best available scientific evidence. Studies have shown that two doses of HPV vaccine given at least six months apart to adolescents at age 9–14 years worked as well or better than three doses given to older adolescents and young adults. Studies have not been done to show this for adolescents starting the series at age 15 years or older.

Gardasil shot contraindications and precautions

A severe allergic reaction (e.g., anaphylaxis) to a vaccine component or following a prior dose of Gardasil vaccine is a contraindication to receipt of Gardasil vaccine.

• Anaphylactic allergy to latex is a contraindication to bivalent Gardasil vaccine in a prefilled syringe since the tip cap might contain natural rubber latex.
• Quadrivalent and 9-valent Gardasil vaccines are produced in Saccharomyces cerevisiae (baker’s yeast) and are contraindicated for persons with a history of immediate hypersensitivity to yeast.
• A moderate or severe acute illness is a precaution to vaccination, and vaccination should be deferred until symptoms of the acute illness improve.
• A minor acute illness (e.g., diarrhea or mild upper respiratory tract infection, with or without fever) is not a reason to defer vaccination.

Gardasil and Pregnancy

Gardasil vaccine is NOT recommended for use during pregnancy.

• Gardasil vaccine has not been causally associated with adverse pregnancy outcomes or with adverse effects on the developing fetus, but data on vaccination during pregnancy are limited.
• Women known to be pregnant should delay initiation of the Gardasil vaccine series until after the pregnancy.
• Pregnancy testing before vaccination is not needed. However, if a woman is found to be pregnant after initiation of the vaccination series, the remainder of the series should be delayed until after she is no longer pregnant. No intervention is indicated.

Gardasil vaccine side effects

Vaccines, like any medicine, can have side effects. Many people who get Gardasil HPV vaccine have no side effects at all. Some people report having very mild side effects, like a sore arm. The most common side effects are usually mild.

A clinical study ⁵ evaluated the safety of Gardasil 9 in 12- through 26-year-old girls and women who had previously been vaccinated with three doses of Gardasil. The time interval between the last injection of Gardasil and the first injection of Gardasil 9 ranged from approximately 12 to 36 months. Individuals were administered Gardasil 9 or saline placebo and safety was evaluated using VRC-aided surveillance for 14 days after each injection of Gardasil 9 or saline placebo in these individuals. The individuals who were monitored included 608 individuals who received Gardasil 9 and 305 individuals who received saline placebo. Few (0.5%) individuals who received Gardasil 9 discontinued due to adverse reactions. The vaccine-related adverse experiences that were observed among recipients of Gardasil 9 at a frequency of at least 1.0% and also at a greater frequency than that observed among saline placebo recipients. Overall the safety profile was similar between individuals vaccinated with Gardasil 9 who were previously vaccinated with Gardasil and those who were naïve to HPV vaccination with the exception of numerically higher rates of injection-site swelling and erythema among individuals who were previously vaccinated with Gardasil.

Common side effects of HPV vaccine include:

• The most common adverse reactions reported during clinical trials of HPV vaccines were local reactions at the site of injection – pain, redness, or swelling in the arm where the shot was given.
• In prelicensure clinical trials, local reactions, such as pain, redness, or swelling, were reported by 20% to 90% of recipients.
• A fever of 100°F (37.8 °C) during the 15 days after vaccination was reported in 10% to 13% of HPV vaccine recipients. A similar proportion of placebo recipients reported an elevated temperature.
• A variety of systemic adverse reactions have been reported by vaccine recipients, including nausea, dizziness, myalgia (muscle pain) and malaise. However, these symptoms occurred with equal frequency among both HPV vaccine and placebo recipients.
• Local reactions generally increased in frequency with increasing doses. However, reports of fever did not increase significantly with increasing doses.
• No serious adverse events have been associated with either any HPV vaccine. Ongoing monitoring is conducted by CDC and the Food and Drug Administration.

Brief fainting spells (syncope) and related symptoms (such as jerking movements) can occur after any medical procedure, including vaccination. Adolescents should be seated or lying down during vaccination and remain in that position for 15 minutes after vaccination. This is to prevent any injuries that could occur from a fall from fainting.

On very rare occasions, severe (anaphylactic) allergic reactions may occur after vaccination. People with severe allergies to any component of a vaccine should not receive that vaccine.

HPV vaccine does not cause HPV infection or cancer. HPV vaccine is made from one protein from the virus, and is not infectious, meaning that it cannot cause HPV infection or cancer. Not receiving HPV vaccine at the recommended ages can leave one vulnerable to cancers caused by HPV.

There are no data that suggest getting HPV vaccine will have an effect on future fertility for women. In fact, getting vaccinated and protecting against HPV-related cancers can help women and families have healthy pregnancies and healthy babies.

Not getting HPV vaccine leaves people vulnerable to HPV infection and related cancers. Treatments for cancers and precancers might include surgery, chemotherapy, and/or radiation, which might cause pregnancy complications or leave someone unable to have children.

Based on the review of available information by FDA and CDC, Gardasil continues to be safe and effective, and its benefits continue to outweigh its risks ⁶.

CDC has not changed its recommendations for use of Gardasil ⁷.  FDA has not made any changes to the prescribing information for how the vaccine is used ⁶.  In addition, FDA routinely reviews manufacturing information, and has not identified any issues affecting the safety, purity and potency of Gardasil.

Public health and safety are priorities for FDA and CDC.  As with all licensed vaccines, they will continue to closely monitor the safety of Gardasil.  FDA and CDC continue to find that Gardasil is a safe and effective vaccine that will potentially benefit the health of millions of women by providing protection against the types of HPV in the vaccine that cause cervical, vulvar and vaginal cancer, genital warts, and other HPV-related genital diseases in females ⁶.

Gardasil risks

With any medicine, including vaccines, there is a chance of side effects. These are usually mild and go away on their own, but serious reactions are also possible.

Most people who get HPV vaccine do not have any serious problems with it.

Mild or moderate problems following HPV vaccine:

Reactions in the arm where the shot was given:

• Soreness (about 9 people in 10)
• Redness or swelling (about 1 person in 3)

Fever:

• Mild (100°F or 37.8 °C) (about 1 person in 10)
• Moderate (102°F or 38.9 °C) (about 1 person in 65)

Other problems:

• Headache (about 1 person in 3)

Problems that could happen after any injected vaccine:

• People sometimes faint after a medical procedure, including vaccination. Sitting or lying down for about 15 minutes can help prevent fainting and injuries caused by a fall. Tell your doctor if you feel dizzy, or have vision changes or ringing in the ears.
• Some people get severe pain in the shoulder and have difficulty moving the arm where a shot was given. This happens very rarely.
• Any medication can cause a severe allergic reaction. Such reactions from a vaccine are very rare, estimated at about 1 in a million doses, and would happen within a few minutes to a few hours after the vaccination.

As with any medicine, there is a very remote chance of a vaccine causing a serious injury or death.

What if there is a serious reaction?

If you think it is a severe allergic reaction or other emergency that can’t wait, call your local emergency number or get to the nearest hospital. Otherwise, call your doctor.

Afterward, the reaction should be reported to the Vaccine Adverse Event Reporting System (VAERS). Your doctor should file this report, or you can do it yourself through the VAERS website (https://vaers.hhs.gov/).

Gardasil vaccine deaths

Across the clinical studies, ten deaths occurred (five each in the Gardasil 9 and Gardasil groups); none were assessed as vaccine-related ⁵. Causes of death in the Gardasil 9 group included one automobile accident, one suicide, one case of acute lymphocytic leukemia, one case of hypovolemic septic shock, and one unexplained sudden death 678 days following the last dose of Gardasil 9. Causes of death in the Gardasil control group included one automobile accident, one airplane crash, one cerebral hemorrhage, one gunshot wound, and one stomach adenocarcinom ⁵.

References

1. Mabeya H, Menon S, Weyers S, et al. Uptake of three doses of HPV vaccine by primary school girls in Eldoret, Kenya; a prospective cohort study in a malaria endemic setting. BMC Cancer. 2018;18:557. doi:10.1186/s12885-018-4382-x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948818/
2. Ferlay J, Soerjomataram I, Ervik M, et al; International Agency for Research on Cancer. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 http://globocan.iarc.fr/Default.aspx
3. Gardasil 9. https://www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts/ucm426445.htm
4. Human Papillomavirus (HPV) Vaccination: What Everyone Should Know. https://www.cdc.gov/vaccines/vpd/hpv/public/index.html
5. https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM426457.pdf
6. Gardasil Vaccine Safety. https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm179549.htm
7. Vaccine Safety. https://www.cdc.gov/vaccinesafety/index.html

What is diphenhydramine

Diphenhydramine is an antihistamine [histamine-1 (H1) receptor blocker or antagonist] medicine that relieves allergy by blocking the action of histamine in your body. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Diphenhydramine is used to relieve red, irritated, itchy, watery eyes; sneezing; and runny nose caused by hay fever, allergies, or the common cold. Diphenhydramine is also used to relieve cough caused by minor throat or airway irritation. Diphenhydramine is also used to prevent and treat motion sickness, and to treat insomnia (difficulty falling asleep or staying asleep). Diphenhydramine is also used to control abnormal movements in people who have early stage parkinsonian syndrome (a disorder of the nervous system that causes difficulties with movement, muscle control, and balance) or who are experiencing movement problems as a side effect of a medication.

Diphenhydramine will relieve the symptoms of these conditions but will not treat the cause of the symptoms or speed recovery. Diphenhydramine should not be used to cause sleepiness in children.

Like other antihistamines, diphenhydramine should be used with caution in infants and young children and should NOT be used in premature or full-term neonates ¹. Children younger than 6 years of age should receive diphenhydramine only under the direction of a physician ¹. Safety and efficacy of diphenhydramine as a nighttime sleep aid in children younger than 12 years of age have not been established ¹. In addition, children may be more prone than adults to paradoxically experience CNS stimulation rather than sedation when antihistamines are used as nighttime sleep aids ¹. Because diphenhydramine may cause marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers), diphenhydramine should be used in children only under the direction of a physician ¹.

Because diphenhydramine has an atropine-like action, it should be used with caution in patients who have asthma ². Patients should be cautioned about taking diphenhydramine with other depressant substances, because of the additive effect. Persons should also be advised not to operate a motor vehicle, fly an airplane, or operate hazardous machinery while on this drug. The incidence of side effects is approximately 30-60% ².

The most frequent side effect of diphenhydramine the first-generation H1 antagonists is sedation. Although sedation may be a desirable adjunct in the treatment of some patients, it may interfere with the patient’s daytime activities ³. Concurrent ingestion of alcohol or other CNS depressants produces an additive effect that impairs motor skills. Other untoward reactions referable to central actions include dizziness, tinnitus, lassitude, incoordination, fatigue, blurred vision, diplopia, euphoria, nervousness, insomnia, and tremors.

What does diphenhydramine do

Diphenhydramine is a first generation antihistamine with sedative and anti-allergic properties. Diphenhydramine competitively inhibits the histamine-1 (H1) receptor, thereby alleviating the symptoms caused by endogenous histamine on bronchial, capillary and gastrointestinal smooth muscles. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and gastrointestinal smooth muscle spasms.

Diphenhydramineis used to treat sneezing, runny nose, watery eyes, hives, skin rash, itching (pruritus), and other cold or allergy symptoms.

Diphenhydramine is also used to treat motion sickness as an antiemetic, antitussive, to induce sleep, and to treat certain symptoms (e.g. tremors) of Parkinson’s disease (off-label use).

Before taking diphenhydramine – Precautions

• tell your doctor and pharmacist if you are allergic to diphenhydramine or any other medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: other diphenhydramine products (even those that are used on the skin); other medications for colds, hay fever, or allergies; medications for anxiety, depression, or seizures; muscle relaxants; narcotic medications for pain; sedatives; sleeping pills; and tranquilizers.
• tell your doctor if you have or have ever had asthma, emphysema, chronic bronchitis, or other types of lung disease; glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision); ulcers; difficulty urinating (due to an enlarged prostate gland); heart disease; high blood pressure; seizures; or an overactive thyroid gland.If you will be using the liquid, tell your doctor if you have been told to follow a low-sodium diet.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking diphenhydramine, call your doctor.
• talk to your doctor about the risks and benefits of taking diphenhydramine if you are 65 years of age or older. Older adults should not usually take diphenhydramine because it is not as safe as other medications that can be used to treat the same conditions.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking diphenhydramine.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• remember that alcohol can add to the drowsiness caused by this medication. Avoid alcoholic beverages while you are taking this medication.
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that some brands of chewable tablets and rapidly disintegrating tablets that contain diphenhydramine may be sweetened with aspartame, a source of phenylalanine.
• Like other antihistamines, diphenhydramine should be used with caution in infants and young children and should not be used in premature or full-term neonates. Children younger than 6 years of age should receive diphenhydramine only under the direction of a physician. Safety and efficacy of diphenhydramine as a nighttime sleep aid in children younger than 12 years of age have not been established. In addition, children may be more prone than adults to paradoxically experience CNS stimulation rather than sedation when antihistamines are used as nighttime sleep aids. Because diphenhydramine may cause marked drowsiness that may be potentiated by other CNS depressants (e.g., sedatives, tranquilizers), the antihistamine should be used in children receiving one of these drugs only under the direction of a physician.

Diphenhydramine and alcohol

Ask your doctor before using diphenhydramine together with ethanol. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking diphenhydramine. Using diphenhydramine together with alcohol increases your risk for overdose. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Diphenhydramine Pregnancy Warnings

Animal models have failed to reveal evidence of impaired fertility or fetal harm at doses up to 5 times the human dose. There are no controlled data in human pregnancy.

• US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Use is recommended only if clearly needed and the benefit outweighs the risk.

I just found out I am pregnant. Should I stop taking diphenhydramine?

You should always talk with your health care provider before making any changes in your medication. It is important to consider the benefits of treating allergy symptoms and other conditions during pregnancy. Treating allergy symptoms may reduce asthma symptoms and the need for more asthma medicine. Allergy treatment can also result in better sleep and emotional well-being.

Can use of diphenhydramine during pregnancy cause birth defects?

It is unlikely that diphenhydramine would cause an increased chance for birth defects. Most studies show no increased chance of birth defects with the use of diphenhydramine in early pregnancy. While one study suggested an increased chance of several types of birth defects, the study does not prove causation and these findings have not been confirmed.

Can use of diphenhydramine cause other pregnancy complications?

At recommended doses, diphenhydramine has not been shown to cause problems in pregnancy. There are rare reports of problems with the use of diphenhydramine in the third trimester. These reports usually involve using more of the medication than is recommended or using it for long-term (chronic) use. High levels of diphenhydramine could cause uterine hyperstimulation (contractions that are too long or too often). Uterine hyperstimulation can affect the developing baby such as increasing the baby’s heart rate. Uterine contractions can also lead to serious complications, including uterine rupture (a tear in the uterus) or placental abruption (when the placenta pulls away from the wall of the uterus before the baby is born).

Also, there are a few reports of withdrawal symptoms in infants whose mothers took diphenhydramine daily throughout pregnancy.

Is there anyone who should avoid taking diphenhydramine during pregnancy?

A single human report and animal data have suggested that the combination of two medications: temazepam (a benzodiazepine) and diphenhydramine may increase the chance for stillbirth or infant death shortly after birth ⁴. It is unknown if this interaction will occur with all medications in the benzodiazepine class. Women taking benzodiazepines should talk with their health care provider before taking diphenhydramine during their pregnancy ⁴.

Diphenhydramine and Breastfeeding

Diphenhydramine has been detected in milk ¹. Because of the potential for serious adverse reactions to antihistamines in nursing infants, a decision should be made whether to discontinue nursing or diphenhydramine, taking into account the importance of the drug to the woman.

Because diphenhydramine can cause sleepiness in adults, it may do the same for the baby ⁵. If you need to take an antihistamine regularly, ask your health care provider if a non-sedating one would work for your symptoms.

Antihistamines, as a group, might lower the amount of milk a woman makes, especially when using long acting antihistamines ⁶ and when used with decongestants like pseudoephedrine or phenylephrine. This is less likely to be of concern in a woman with established milk supply (has been breastfeeding for a while).

Two studies ⁷ with women who used an antihistamine (not just diphenhydramine) while breastfeeding reported their babies were irritable, sleepier, and/or slept less.

Be sure to discuss any medications you are taking and your options for breastfeeding with your health care provider as well as the baby’s pediatrician.

What is diphenhydramine used for

Diphenhydramine uses

• Temporarily relieves these symptoms due to hay fever or other upper respiratory allergies:
  • Runny nose
  • Sneezing
  • Itchy, watery eyes
  • Itching of the nose or throat
• Temporarily relieves these symptoms due to the common cold:
  • Runny nose
  • Sneezing

Diphenhydramine dosage

Applies to the following strengths diphenhydramine: 50 mg/mL; 12.5 mg; 25 mg; 12.5 mg/5 mL; 50 mg; 10 mg/mL; 19 mg; 6.25 mg/5 mL; 25 mg/5 mL; 50 mg/30 mL; 6.25 mg/mL

Usual Adult Dose for Insomnia

• Diphenhydramine Citrate: 76 mg orally once a day at bedtime
• Diphenhydramine Hydrochloride (diphenhydramine HCL): 50 mg orally once a day at bedtime

Comment:

Patients should contact their healthcare provider if symptoms of insomnia persist for more than 2 weeks while receiving treatment.

Uses:

• As a nighttime sleep aid
• To reduce difficulty falling asleep
• Relief of occasional sleeplessness

Usual Adult Dose for Motion Sickness

Oral:

• Prescription formulations: 25 to 50 mg orally 3 to 4 times a day, with the first dose given 30 minutes before exposure to motion and repeated before meals and upon retiring throughout the duration of the journey.

• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Use:

Active and prophylactic treatment of motion sickness

Usual Adult Dose for Allergic Rhinitis

Oral:

• Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
  • Maximum dose: 456 mg/day
• Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
  • Maximum dose: 300 mg/day
• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Allergic conjunctivitis due to foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Amelioration of allergic reactions to blood or plasma
• Dermatographism
• Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Cold Symptoms

Oral:

• Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
  • Maximum dose: 456 mg/day
• Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
  • Maximum dose: 300 mg/day
• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Allergic conjunctivitis due to foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Amelioration of allergic reactions to blood or plasma
• Dermatographism
• Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Pruritus

Oral:

• Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
  • Maximum dose: 456 mg/day
• Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
  • Maximum dose: 300 mg/day
• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Allergic conjunctivitis due to foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Amelioration of allergic reactions to blood or plasma
• Dermatographism
• Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Urticaria

Oral:

• Diphenhydramine Citrate: 38 to 76 mg orally every 4 to 6 hours as needed
  • Maximum dose: 456 mg/day
• Diphenhydramine Hydrochloride (diphenhydramine HCL): 25 to 50 mg orally every 4 to 6 hours as needed
  • Maximum dose: 300 mg/day
• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Allergic conjunctivitis due to foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Amelioration of allergic reactions to blood or plasma
• Dermatographism
• Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Adult Dose for Extrapyramidal Reaction

• Oral: 25 to 50 mg orally 3 to 4 times a day
• Parenteral: 10 to 50 mg deep IM or IV as needed, and may increase to 100 mg if required
  • Maximum dose: 400 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Parkinsonism of the elderly who are unable to tolerate more potent agents
• Mild cases of parkinsonism in other age groups
• Other cases of parkinsonism in combination with centrally acting anticholinergic agents

Usual Pediatric Dose for Allergic Rhinitis

Prescription formulations:

1 month and older:

Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used

-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:

6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed

• Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed

• Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

• Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

• Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

• Maximum dose: 300 mg/day

Comments:

• IV injection rates should not exceed 25 mg/min.
• To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring throughout the duration of the journey.
  

Uses:

• Active and prophylactic treatment of motion sickness
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Cold Symptoms

Prescription formulations:

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:

6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed
-Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed
-Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

• Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

• Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

• Maximum dose: 300 mg/day

Comments:

• IV injection rates should not exceed 25 mg/min.
• To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring
• Throughout the duration of the journey.

Uses:

• Active and prophylactic treatment of motion sickness
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Motion Sickness

Prescription formulations:
1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Oral Over-the-Counter (OTC) formulations:

Diphenhydramine Citrate:
6 to 12 years: 19 to 38 mg orally every 4 to 6 hours as needed
-Maximum dose: 228 mg/day

12 years and older: 38 to 76 mg orally every 4 to 6 hours as needed
-Maximum dose: 456 mg/day

Diphenhydramine Hydrochloride (diphenhydramine HCL):

2 to 6 years: 6.25 mg orally every 4 to 6 hours as needed

• Maximum dose: 37.5 mg/day

6 to 12 years: 12.5 to 25 mg orally every 4 to 6 hours as needed

• Maximum dose: 150 mg/day

12 years and older: 25 to 50 mg orally every 4 to 6 hours as needed

• Maximum dose: 300 mg/day

Comments:

• IV injection rates should not exceed 25 mg/min.
• To prevent motion sickness, the first dose should be given 30 minutes before exposure to motion and should be repeated before meals and upon retiring
• hroughout the duration of the journey.

Uses:

• Active and prophylactic treatment of motion sickness
• Temporary relief of runny nose, itchy, watery eyes, sneezing, and itching of the nose/throat due to hay fever or other upper respiratory allergies
• Temporarily relieves runny nose and sneezing due to the common cold

Usual Pediatric Dose for Insomnia

12 years and older:

• Diphenhydramine citrate: 76 mg orally once a day at bedtime
• Diphenhydramine hydrochloride (diphenhydramine HCL): 50 mg orally once a day at bedtime

Comment:

Patients should contact their healthcare provider if symptoms of insomnia persist for more than 2 weeks while receiving treatment.

Uses:

• As a nighttime sleep aid
• To reduce difficulty falling asleep
• Relief of occasional sleeplessness

Usual Pediatric Dose for Extrapyramidal Reaction

Prescription formulations

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Mild cases of parkinsonism
• Other cases of parkinsonism, including drug-induced, in combination with centrally acting anticholinergic agents

Usual Pediatric Dose for Allergic Reaction

Prescription formulations

1 month and older:
Oral: 12.5 to 25 mg orally 3 to 4 times a day; alternatively, weight-based dosing of 5 mg/kg orally per day OR body surface area dosing of 150 mg/m2 orally per day may be used
-Maximum dose: 300 mg/day

Parenteral: 1.25 mg/kg deep IM or IV 4 times a day OR 37.5 mg/m2 deep IM or IV 4 times a day
-Maximum dose: 300 mg/day

Comment:

IV injection rates should not exceed 25 mg/min.

Uses:

• Allergic conjunctivitis due to foods
• Mild, uncomplicated allergic skin manifestations of urticaria and angioedema
• Amelioration of allergic reactions to blood or plasma
• Dermatographism
• Therapy for anaphylactic reactions adjunctive to epinephrine and other standard measures after acute manifestations have been controlled

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dialysis

Data not available

How should diphenhydramine be used?

Diphenhydramine comes as a tablet, a rapidly disintegrating (dissolving) tablet, a capsule, a liquid-filled capsule, a dissolving strip, powder, and a liquid to take by mouth. When diphenhydramine is used for the relief of allergies, cold, and cough symptoms, it is usually taken every 4 to 6 hours. When diphenhydramine is used to treat motion sickness, it is usually taken 30 minutes before departure and, if needed, before meals and at bedtime. When diphenhydramine is used to treat insomnia it is taken at bedtime (30 minutes before planned sleep). When diphenhydramine is used to treat abnormal movements, it is usually taken three times a day at first and then taken 4 times a day. Follow the directions on the package or on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take diphenhydramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor or directed on the label.

Diphenhydramine comes alone and in combination with pain relievers, fever reducers, and decongestants. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using two or more products at the same time. These products may contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.

Nonprescription cough and cold combination products, including products that contain diphenhydramine, can cause serious side effects or death in young children. Do not give these products to children younger than 4 years of age. If you give these products to children 4 to 11 years of age, use caution and follow the package directions carefully.

If you are giving diphenhydramine or a combination product that contains diphenhydramine to a child, read the package label carefully to be sure that it is the right product for a child of that age. Do not give diphenhydramine products that are made for adults to children.

Before you give a diphenhydramine product to a child, check the package label to find out how much medication the child should receive. Give the dose that matches the child’s age on the chart. Ask the child’s doctor if you don’t know how much medication to give the child.

If you are taking the liquid, do not use a household spoon to measure your dose. Use the measuring spoon or cup that came with the medication or use a spoon made especially for measuring medication.

If you are taking the dissolving strips, place the strips on your tongue one at a time and swallow after they melt.

If you are taking the rapidly dissolving tablets, place a tablet on your tongue and close your mouth. The tablet will quickly dissolve and can be swallowed with or without water.

If you are taking the capsules, swallow them whole. Do not try to break the capsules.

What should I do if I forget a dose?

Diphenhydramine is usually taken as needed. If your doctor has told you to take diphenhydramine regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Diphenhydramine side effects

The most commonly reported side effects included somnolence, dizziness, and incoordination.

Diphenhydramine may cause side effects. Numerous side effects including drowsiness, confusion, restlessness, nausea, vomiting, diarrhea, blurring of vision, diplopia, difficulty in urination, constipation, nasal stuffiness, vertigo, palpitation, headache, and insomnia ². Other side effects observed were urticaria, drug rash, photosensitivity, hemolytic anemia, hypotension, epigastric distress, anaphylactic shock, tightness of the chest and wheezing, thickening of bronchial secretions, dryness of the mouth, nose and throat and tingling, and heaviness and weakness of the hands ².

Prolonged use of antihistamines … may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort ⁸.

Tell your doctor if any of these symptoms are severe or do not go away:

• dry mouth, nose, and throat
• drowsiness
• dizziness
• nausea
• vomiting
• loss of appetite
• constipation
• increased chest congestion
• headache
• muscle weakness
• excitement (especially in children)
• nervousness

Some side effects may be serious. If you experience any of the following symptoms, call your doctor immediately:

• vision problems
• difficulty urinating or painful urination

Diphenhydramine may cause other side effects. Call your doctor if you experience any unusual problems while you are taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch/default.htm)

Common side effects

The most common side effect of diphenhydramine is feeling sleepy and tired. This happens in more than 1 in 10 people. Talk to your doctor or pharmacist if this side effect bothers you or won’t go away.

Other common side effects of diphenhydramine happen in more than 1 in 100 people. Talk to your doctor or pharmacist if these side effects bother you or won’t go away:

• dry mouth
• feeling dizzy

Common side effects of diphenhydramine mixed with pseudoephedrine happen in more than 1 in 100 people. They include:

• difficulty sleeping
• hallucinations
• rashes
• difficulty peeing in men – especially men with an enlarged prostate

Nervous system

• Common (1% to 10%): Sedation/somnolence/sleepiness, drowsiness, unsteadiness, dizziness, headache, attention disturbance
• Rare (0.01% to 0.1%): Extrapyramidal effects, tremor, convulsions
• Frequency not reported: Paresthesia, dyskinesia/muscle dyskinesia, vertigo, neuritis, incoordination, psychomotor impairment, activation of epileptogenic foci.

Drowsiness usually diminishes after a few days.

Gastrointestinal

• Common (1% to 10%): Dry mouth
• Frequency not reported: Gastrointestinal disturbance, nausea, vomiting, constipation, diarrhea, dyspepsia, epigastric distress

Other

• Common (1% to 10%): Fatigue
• Frequency not reported: Lassitude, tinnitus, acute labyrinthitis, asthenia, chills, impaired performance (including impaired driving, work, and/or information processing)

Psychiatric

• Rare (0.01% to 0.1%): Confusion, depression, sleep disturbances
• Frequency not reported: Paradoxical excitation/excitation, agitation, increased energy, restlessness, nervousness, euphoria, anxiety, hallucinations, insomnia, irritability

Cardiovascular

• Rare (0.01% to 0.1%): Palpitations, hypotension, arrhythmia
• Frequency not reported: Tachycardia, chest tightness, extrasystoles

Hematologic

• Rare (0.01% to 0.1%): Blood disorders
• Frequency not reported: Hemolytic anemia, thrombocytopenia, agranulocytosis

Hypersensitivity

• Rare (0.01% to 0.1%): Hypersensitivity reactions
• Frequency not reported: Angioedema, anaphylactic shock

Hepatic

• Rare (0.01% to 0.1%): Liver dysfunction

Dermatologic

• Frequency not reported: Rash, urticaria, skin rashes, erythema, photosensitivity, pruritus, drug rash, excessive perspiration

Respiratory

• Frequency not reported: Dyspnea, thickening of bronchial secretions, throat tightening, wheezing, nasal stuffiness, dry nose or throat

Genitourinary

• Frequency not reported: Urinary hesitancy/difficulty/retention, dysuria, early menses

Ocular

• Frequency not reported: Blurred vision, dry eyes, diplopia

Metabolic

• Frequency not reported: Increased appetite, anorexia

Musculoskeletal

• Frequency not reported: Muscle twitching/weakness

Serious side effects

In rare cases, it’s possible to have a serious allergic reaction to diphenhydramine.

The warning signs of serious allergic reaction are:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• wheezing
• tightness in the chest or throat
• having trouble breathing or talking
• swelling of the mouth, face, lips, tongue, or throat

These are not all the side effects of diphenhydramine. For a full list see the leaflet inside your medicines packet.

How to cope with side effects

What to do about:

• feeling sleepy – try a different non-drowsy antihistamine. If this doesn’t help, talk to your doctor.
• dry mouth chew sugar-free gum or suck sugar-free sweets.
• feeling dizzy – lie down until the dizziness passes, then get up slowly. Move slowly and carefully. Avoid coffee, cigarettes, alcohol and recreational drugs. If the dizziness doesn’t get better within a couple of days, speak to your pharmacist or doctor.

Diphenhydramine overdose

Diphenhydramine overdose occurs when someone takes more than the normal or recommended amount of this medicine. This can be by accident or on purpose.

In case of diphenhydramine overdose, get medical help or contact a Poison Control Center helpline at 1-800-222-1222 right away!

Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

Excessive diphenhydramine doses may cause flushing, tachycardia, blurred vision, delirium, toxic psychosis, urinary retention, and respiratory depression ⁹.

Overdosage of diphenhydramine may result in the development of anticholinergic symptoms, seizures, and coma ¹⁰. A fatal outcome following a diphenhydramine overdose does not commonly occur. This report describes an overdosage of diphenhydramine (7.5 g) which resulted in the death of a 14-year-old girl ¹⁰. The patient initially developed seizures following by cardiac conduction and hemodynamic compromise resulting in death despite life support measures.

Symptoms of diphenhydramine overdose

Below are symptoms of a diphenhydramine overdose in different parts of the body ¹¹.

Bladder and Kidneys

• Inability to urinate

Eyes, ears, nose, mouth and throat

• Blurred vision
• Dry mouth
• Enlarged pupils
• Very dry eyes
• Ringing in the ears

Heart and blood vessels

• Low blood pressure
• Rapid heartbeat

Nervous system

• Agitation
• Confusion
• Seizures
• Delirium
• Depression
• Drowsiness
• Hallucinations (seeing or hearing things that aren’t there)
• Increased sleepiness
• Nervousness
• Tremor
• Unsteadiness

Skin

• Dry, red skin

Stomach and intestines

• Nausea
• Vomiting

What to Expect at the Emergency Room

Take the container to the hospital with you, if possible.

The health care provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure.

Tests that may done include ¹²:

• Blood and urine tests
• Chest x-ray
• ECG (electrocardiogram or heart tracing)

Treatment may include ¹²:

• Fluids through a vein (by IV)
• Medicines to treat symptoms
• Activated charcoal
• Laxative
• Breathing support, including a tube through the mouth into the lungs and connected to a breathing machine (ventilator)

Outlook (Prognosis)

Recovery is likely if the person survives the first 24 hours. Complications such as pneumonia, muscle damage from lying on a hard surface for a long period of time, or brain damage from lack of oxygen may result in permanent disability.

Few people actually die from an antihistamine overdose. However, serious heart rhythm disturbances may occur, which can cause death.

Keep all medicines in child-proof bottles and out of reach of children.

Case reports

A 13-month-old male who ingested 20 diphenhydramine (25 mg) tablets presented with seizures and ultimately progressed to status epilepticus and wide-complex tachycardia ¹³. Due to worsening clinical course, hemodialysis was performed with temporal resolution of his symptoms. Hemodialysis may be considered in critically ill diphenhydramine overdoses not responsive to conventional supportive care.

Case report

Diphenhydramine toxicity manifests with signs of anticholinergic toxicity; therapy is generally supportive ¹⁴. In rare cases, patients can also present with a wide complex tachycardia due to sodium channel blockade. Treatment involves sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine (octanol/water partition coefficient of 3.3), successful use of intravenous fat emulsion after a confirmed sole ingestion of diphenhydramine is not previously reported. This case study ¹⁴ present the case of a 30-year-old woman presenting with seizures, a wide complex tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine refractory to other therapies with rapid improvement after intravenous fat emulsion administration.

Case report

Overdosage of diphenhydramine may result in the development of anticholinergic symptoms, seizures, and coma ¹⁵. A fatal outcome following a diphenhydramine overdose does not commonly occur. This report describes /an/ overdosage of diphenhydramine (7.5 g) which resulted in the death of a 14-year-old girl. The patient initially developed seizures following by cardiac conduction and hemodynamic compromise resulting in death despite life support measures ¹⁵.

Case report

Overdosage and toxicity (including death) have been reported in children younger than 2 years of age receiving nonprescription (over-the-counter, OTC) preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection ¹. There is limited evidence of efficacy for these preparations in this age group, and appropriate dosages (i.e., approved by the US Food and Drug Administration [FDA]) for the symptomatic treatment of cold and cough have not been established ¹. Therefore, FDA stated that nonprescription cough and cold preparations should not be used in children younger than 2 years of age; the agency continues to assess safety and efficacy of these preparations in older children. Meanwhile, because children 2-3 years of age also are at increased risk of overdosage and toxicity, some manufacturers of oral nonprescription cough and cold preparations recently have agreed to voluntarily revise the product labeling to state that such preparations should not be used in children younger than 4 years of age. Because FDA does not typically request removal of products with previous labeling from pharmacy shelves during a voluntary label change, some preparations will have the new recommendation (“do not use in children younger than 4 years of age”), while others will have the previous recommendation (“do not use in children younger than 2 years of age”). FDA recommends that parents and caregivers adhere to the dosage instructions and warnings on the product labeling that accompanies the preparation if administering to children and consult with their clinician about any concerns.

Case report

Two cases of diphenhydramine-containing hypnotics overdose, exhibiting delirium and involuntary choreic movement were identified ¹⁶. In case 1, a 32-year-old man ingested 24 tablets of Drewell, each containing 25 mg diphenhydramine, in a suicidal attempt. About four hours after ingestion, he showed generalized convulsion, delirium, and involuntary choreic movements ¹⁶. Intravenous diazepam was ineffective and he was sedated with continuous infusion of propofol. About 15 hours after ingestion and on discontinuing the sedation, he became alert and did not show any neurological abnormality. The blood concentration of diphenhydramine, measured by liquid chromatography/electrospray mass spectrometry, was 1.26 ug/ mL. In case 2, a 24-year-old woman ingested 114 tablets of Drewell and was admitted to a hospital ¹⁶. Her consciousness was impaired and she was treated with intravenous fluids. About four hours after ingestion, she became restless and showed confusion, agitation, and involuntary choreic movements ¹⁶. Sedation with continuous propofol infusion was required. She awoke the next day on discontinuing the sedation, and she did not show any neurological abnormalities. The blood concentration of diphenhydramine was 2.37 ug/mL. It is suggested that physicians should be aware of psychotic-like symptoms and choreic involuntary movement in patients with diphenhydramine-containing hypnotics overdose ¹⁶.

Case report

A 13-month-old infant girl was brought in by the emergency medical service for a witnessed tonic-clonic seizure ¹⁷. Two hours previously, the child had been found with an open bottle of 25-mg diphenhydramine tablets, 24 of which were missing. Midazolam was administered with seizure resolution ¹⁷. Examination revealed 4-mm reactive pupils; nystagmus; warm, dry, flushed skin; and altered mental status. Initial electrocardiograms revealed sinus tachycardia at a rate of 180 beats per minute, a prolonged QRS of 130 milliseconds (from a baseline of 65 milliseconds), and a positive terminal R wave in aVR, which later resolved after sodium bicarbonate treatment. The patient was discharged home the following day with no sequelae ¹⁷.

Case report

A 36-year-old woman with a medical history of hypothyroidism on levothyroxine was brought to the emergency department with active seizures by emergency medical services after what was later determined to be a diphenhydramine overdose ¹⁸. One hour after an argument with her husband he found her lethargic in a locked room. Initial vital signs were: blood pressure, 90/55 mmHg; heart rate, 160 beats/min; respiratory rate 18 breaths/min; room air oxygen saturation, 99%; temperature, 99.8 deg F; rapid point-of-care glucose, 130 mg/dL. The generalized seizures continued for duration of 30 min, despite the intravenous administration of 8 mg of lorazepam. The patient underwent endotracheal intubation and a propofol infusion terminated her seizures. An electrocardiogram after the status was terminated which revealed a wide-complex tachycardia with QRS duration of 127 ms. The QRS narrowed after 200 mEq of intravenous sodium bicarbonate was administrated. The patient was neurologically intact upon extubation on hospital day 2. The serum diphenhydramine concentration drawn on arrival to the ED was 1200 ng/mL (9-120 ng/mL); a tricyclic screen was negative. While seizures and sodium channel blockade are recognized complications of diphenhydramine toxicity, reported cases of status epilepticus from diphenhydramine overdose are rare. Elements of the patient’s presentation were similar to a tricyclic overdose and management required aggressive control of her seizures, sodium bicarbonate therapy, and recognizing that physostigmine was contraindicated due to wide complex tachycardia. Diphenhydramine overdose may cause status epilepticus and wide-complex tachycardia. Management should focus on antidotal therapy with sodium bicarbonate and supportive neurological management with appropriate anticonvulsants and airway protection if clinically indicated ¹⁸.

Case report

Drug- and toxin-induced rhabdomyolysis is a nonspecific clinical syndrome resulting from the release of skeletal muscle cell contents into the plasma and urine. Antihistamine drugs are the active ingredients in a number of over-the-counter preparations and are frequently ingested in suicide attempts. The authors report rhabdomyolysis as a rare adverse effect of diphenhydramine toxicity in a 29-year-old man who ingested an unknown quantity of an over-the-counter sleep preparation in a suicide attempt ¹⁹. The patient had documented toxic concentration of diphenhydramine in his cerebrospinal fluid and no history of seizures, coma, or hypothermia. A high index of suspicion and an evaluation for rhabdomyolysis is warranted in antihistamine toxicity.

Case report

A case of electrocardiographic signature of the Brugada syndrome: a genetic condition that causes disruption of the heart’s normal rhythm in a 39-year-old patient with an overdose of diphenhydramine is reported ²⁰. He was found unconscious and hypotensive. His serum potassium concentration was 8.3 mEq/L and the ECG revealed a coved-type ST-segment elevation in leads V2-V3. These repolarization abnormalities neither normalize with the correction of the hyperkalemia nor with an intravenous infusion of isoproterenol. When he regained consciousness, he was admitted the toxic ingestion of diphenhydramine and progressively the ECG normalized. A negative flecainide test confirmed that the transient ECG abnormalities were the consequence of the drug overdose and ruled out the Brugada syndrome ²⁰.

Case report

Diphenhydramine it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death ²¹. Reports of fatal intoxications in young children are rare. The authors present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old ²¹. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child’s father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle ²¹. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities ²¹.

Case report

Diphenhydramine toxicity (e.g., dilated pupils, facial flushing, hallucinations, ataxic gait, urinary retention) has been reported in pediatric patients (19 months to 9 years of age) following topical application of diphenhydramine to large areas of the body (often areas with broken skin) or following concomitant use of topical and oral preparations containing the drug for self-medication in the symptomatic management of pain and pruritus associated with varicella (chickenpox), poison ivy, or sunburn ¹. Manifestations typically resolved within 48 hours following discontinuance of the drug, and no deaths have been reported following topical use of diphenhydramine alone.

References

1. American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 10
2. Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1545
3. Brunton, L. Chabner, B, Knollman, B. Goodman and Gillman’s The Pharmaceutical Basis of Therapeutics, Twelth Edition, McGraw Hill Medical, New York, NY. 2011, p. 923
4. Benzodiazepines. https://mothertobaby.org/fact-sheets/benzodiazepines-pregnancy/pdf/
5. Ito S, Blajchman A, Stephenson M et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-9. https://www.ncbi.nlm.nih.gov/pubmed/8498418
6. Messinis IE, Souvatzoglou A, Fais N et al. Histamine H1 receptor participation in the control of prolactin secretion in postpartum. J Endocrinol Invest. 1985;8:143-6. https://www.ncbi.nlm.nih.gov/pubmed/3928731
7. USP Convention. USPDI – Drug Information for the Health Care Professional. 16th ed. Volume I. Rockville, MD: U.S. Pharmaceutical Convention, Inc. 1996 (Plus updates)., p. 327
8. USP Convention. USPDI – Drug Information for the Health Care Professional. 15 th ed. Volume 1. Rockville, MD: United States Pharmacopeial Convention, Inc., 1995. (Plus updates.), p. 306
9. OLSON, K.R. (Ed). Poisoning and Drug Overdose, Sixth Edition. McGraw-Hill, New York, NY 2012, p. 478
10. Krenzelok EP et al; Ann Emerg Med 11 (4): 212-3; 1982 https://www.ncbi.nlm.nih.gov/pubmed/7073039
11. Aronson JK. Anticholinergic drugs. In: Aronson JK, ed. Meyler’s Side Effects of Drugs. 16th ed. Waltham, MA: Elsevier; 2016:534-539.
12. Monte AA, Hoppe JA. Anticholinergics. In: Walls RM, Hockberger RS, Gausche-Hill M, eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 9th ed. Philadelphia, PA: Elsevier; 2018:chap 145.
13. McKeown NJ, West PL, Hendrickson RG, Horowitz BZ. Survival after Diphenhydramine Ingestion with Hemodialysis in a Toddler. Journal of Medical Toxicology. 2011;7(2):147-150. doi:10.1007/s13181-010-0116-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724430/
14. Life-threatening diphenhydramine toxicity presenting with seizures and a wide complex tachycardia improved with intravenous fat emulsion. Am J Ther. 2014 Nov-Dec;21(6):542-4. doi: 10.1097/MJT.0b013e318281191b. https://www.ncbi.nlm.nih.gov/pubmed/24096706
15. Massive diphenhydramine overdose resulting in death. Ann Emerg Med. 1982 Apr;11(4):212-3. https://www.annemergmed.com/article/S0196-0644(82)80501-5/pdf
16. [Diphenhydramine poisoning presented with psychotic-like symptoms and choreic involuntary movement: report of two cases]. Chudoku Kenkyu. 2007 Apr;20(2):125-9. https://www.ncbi.nlm.nih.gov/pubmed/17533963
17. Wide complex tachycardia in a pediatric diphenhydramine overdose treated with sodium bicarbonate. Pediatr Emerg Care. 2011 Dec;27(12):1175-7. doi: 10.1097/PEC.0b013e31823b0e47 https://www.ncbi.nlm.nih.gov/pubmed/22158278
18. JANG DH, MANINI AF, TRUEGER NS, et al. Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clinical toxicology (Philadelphia, Pa). 2010;48(9):945-948. doi:10.3109/15563650.2010.527850. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091778/
19. Emadian SM et al; Am J Emerg Med 14 (6): 574-6; 1996 https://www.ncbi.nlm.nih.gov/pubmed/8857809
20. Lopez-Barbeito B et al; Pacing Clin Electrophysiol 28 (7): 730-2;2005 https://www.ncbi.nlm.nih.gov/pubmed/16008813
21. Baker AM et al; J Forensic Sci 48 (2): 425-8;2003 https://www.ncbi.nlm.nih.gov/pubmed/12665005

What is cetirizine

Cetirizine or cetirizine hydrochloride (cetirizine HCL) is a non-drowsy antihistamine medicine that relieves the symptoms of allergies by blocking the effects of the chemical histamine in your body. Histamine is a chemical that’s released by Mast cells in your body when an allergen is encountered that can produce symptoms of sneezing, hives, itching, watery eyes, and runny nose, also known as hypersensitivity reactions. Cetirizine is much less likely to make you feel sleepy than some other first generation or older antihistamines. Cetirizine was the first marketed drug from the series of second-generation antihistamines showing both minimal side effects on the central nervous system and a reduced level of cardiotoxicity ¹.

Cetirizine’s International Union of Pure and Applied Chemistry (IUPAC) name is 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid) ¹.

When you come into contact with something you’re allergic to, such as pollen, animal hair or fur, house dust or insect bites and stings, your body produces a chemical called histamine. Usually histamine is a useful substance but in an allergic reaction it causes unpleasant symptoms including itchy, watery eyes, running or blocked nose, sneezing and skin rashes.

Cetirizine blocks the effects of histamine and reduces these symptoms.

Key facts:

• It’s usual to take cetirizine once a day. Children sometimes take it twice a day.
• Cetirizine is classed as a non-drowsy antihistamine, but some people still find it makes them feel quite sleepy.
• Common side effects include headache, dry mouth, feeling sick, dizziness, tummy pain and diarrhea.
• It’s best not to drink alcohol while you’re taking cetirizine as it can make you feel sleepy.
• Cetirizine is sold under the trade names Benadryl Allergy, Piriteze, Zirtec, Zyrtec, and Reactine.

Cetirizine is available on prescription. You can also buy it from pharmacies and supermarkets.

Cetirizine comes as tablets, capsules and as a liquid that you swallow.

Despite cetirizine is being marketed as a non-drowsy antihistamine, it may still impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of cetirizine.

Tell your doctor if you regularly use other medicines that make you sleepy (such as other cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by cetirizine. Call your doctor if your symptoms do not improve, if they get worse, or if you also have a fever.

How should cetirizine be used?

Cetirizine comes as a tablet, a chewable tablet, an extended release tablet, and a syrup (liquid) to take by mouth. It is usually taken once a day with or without food. Take cetirizine at around the same time every day. Follow the directions on your package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take cetirizine exactly as directed. Do not take more or less of it or take it more often than directed on the package label or as recommended by your doctor.

Do not use cetirizine to treat hives that are bruised or blistered, that are an unusual color, or that do not itch. Call your doctor if you have these types of hives.

Stop taking cetirizine and call your doctor if your hives do not improve during the first 3 days of your treatment or if your hives last longer than 6 weeks. If you do not know the cause of your hives, call your doctor.

If you are taking cetirizine to treat hives, and you develop any of the following symptoms, get emergency medical help right away: difficulty swallowing, speaking, or breathing; swelling in and around the mouth or swelling of the tongue; wheezing; drooling; dizziness; or loss of consciousness. These may be symptoms of a life-threatening allergic reaction called anaphylaxis. If your doctor suspects that you may experience anaphylaxis with your hives, he may prescribe an epinephrine injector (EpiPen). Do not use cetirizine in place of the epinephrine injector.

How long does it take for cetirizine to work?

Cetirizine starts to work within 30 – 60 minutes after being taken. You should start to feel better within an hour.

How long should I take cetirizine for?

It depends on why you’re taking cetirizine.

You may only need to take it for a short time or as a one-off dose. For example, if you have a reaction to an insect bite, you may only need to take cetirizine for a day or 2.

You may need to take cetirizine for longer if you’re taking it to prevent symptoms – for example, to stop hay fever when the pollen count is high.

Talk to your doctor or pharmacist if you’re unsure how long you need to take cetirizine for.

Is it safe to take cetirizine for a long time?

Cetirizine is unlikely to do you any harm if you take it for a long time. However, it’s best to take cetirizine only for as long as you need to.

Can I drink alcohol with cetirizine?

It’s best not to drink alcohol while you’re taking cetirizine as it can make you feel sleepy.

Is there any food or drink I need to avoid?

You can eat and drink normally while taking cetirizine.

Can I drive or ride a bike with cetirizine?

Cetirizine is classed as a non-drowsy antihistamine but it’s still possible to feel sleepy after taking it.

If this happens to you, don’t drive a car or ride a bike until you feel better.

What’s the difference between cetirizine and other antihistamines?

Cetirizine is known as a non-drowsy antihistamine. That’s because it’s less likely to make you feel sleepy than other, so-called sedating antihistamines such as Benadryl (diphenhydramine).

Most people prefer to take a non-drowsy antihistamine instead of a sedating one. An exception is when you want the medicine to make you sleepy, for example if you have itchy skin that’s keeping you awake.

What’s the difference between cetirizine and other non-drowsy antihistamines?

Other non-drowsy antihistamines like Loratadine, Desloratadine, Fexofenadine, Levocetirizine seem to work just as well as cetirizine.

However, cetirizine seems to be more likely to make you feel sleepy than loratadine, desloratadine or fexofenadine.

Can I take cetirizine with painkillers?

Yes, you can take cetirizine together with Tylenol (acetaminophen) or Motrin (ibuprofen).

Can I take more than one antihistamine together?

Sometimes doctors recommend that people with severe itchy skin rash take 2 different antihistamines together for a few days.

As well as taking a non-drowsy antihistamine during the day (such as cetirizine or loratadine), your doctor may advise that you take a sedating antihistamine at night time if the itch is making it difficult to sleep.

Do not take 2 antihistamines together unless recommended by your doctor.

Can I take cetirizine with other hay fever treatments?

Yes, it’s fine to take cetirizine together with other hay fever treatments, for example steroid nasal sprays (such as Beconase, Rhinacort Aqua and Flixonase Nasules) or eye drops.

Will cetirizine affect my fertility?

There’s no evidence that cetirizine affects male or female fertility.

Will cetirizine affect my contraception?

Cetirizine does not affect any type of contraception including the contraceptive pill and the morning after pill.

Can lifestyle changes relieve hay fever?

It will help if you don’t spend too much time outside if the pollen count is high. Also:

Tips for when you’re outside:

• Don’t cut grass or walk on grass.
• Wear wraparound sunglasses to stop pollen getting into your eyes.
• Put Vaseline around your nostrils to help trap pollen.
• Shower and change your clothes after you’ve been outside to wash off pollen.

Tips for when you’re inside:

• Keep windows and doors shut as much as possible.
• Vacuum regularly and dust with a damp cloth.
• Don’t keep fresh flowers in the house.
• Don’t smoke or be around smoke as it makes hay fever symptoms worse.

Who can and can’t take cetirizine

Cetirizine tablets and liquid that you buy from pharmacies and supermarkets can be taken by adults and children aged 6 and older.

Children over the age of 2 can also take liquid cetirizine for hay fever and skin allergies.

Cetirizine can also be taken under medical supervision by children aged 1 year and older.

Cetirizine isn’t suitable for some people. Tell your doctor or pharmacist if you:

• have had an allergic reaction to cetirizine or any other medicines in the past
• have an allergy to peanuts or soya
• have an allergy to the food additives, E218 or E216
• have an intolerance to, or cannot absorb, some sugars such as lactose or sorbitol
• have liver or kidney failure
• have epilepsy or another health problem that puts you at risk of fits
• have an illness that means you’re more likely to retain urine
• are booked to have an allergy test – taking cetirizine may affect the results, so you might need to stop taking it a few days before the test

Pregnancy and breastfeeding

You can take cetirizine while you’re pregnant. However a similar antihistamine called loratadine is normally used first because there’s more information to say that it’s safe.

• Cetirizine isn’t thought to be harmful during pregnancy, but as very few pregnant women have been studied, it is not possible to be certain.

Talk to your doctor about the benefits and possible harms of taking cetirizine. It will also depend on how many weeks pregnant you are and the reason you need to take cetirizine.

To assess the safety of cetirizine during pregnancy, a prospective observational cohort study with data from 1992 until 2006 was conducted ². Pregnancy outcome was compared between a cohort of pregnant women exposed to cetirizine during the first trimester (n=196) and a control group not exposed to potential teratogens (n=1686). Major birth defects were not more common in the study group than in the control group ². The investigators also compared the crude rate of spontaneous abortions of preterm deliveries and the birth weight of term newborns. This prospective observational study on cetirizine in pregnancy suggests that the use of cetirizine is relatively safe during the first trimester ².

Cetirizine and breastfeeding

It’s usually safe to take cetrizine if you’re breastfeeding as only small amounts get into breast milk.

However, speak to your doctor before taking cetirizine if your baby was premature, had a low birth weight or has other health problems.

Before taking cetirizine

• tell your doctor and pharmacist if you are allergic to cetirizine, hydroxyzine (Vistaril), or any other medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antidepressants, medications for anxiety, medications for mental illness, medications for seizures, other medications for cold and allergy, sedatives, sleeping pills, tranquilizers, and theophylline (Theo-24, Theolair). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking cetirizine, call your doctor.
• you should know that cetirizine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• remember that alcohol can add to the drowsiness caused by this medication. Avoid drinking alcoholic beverages while taking this medication.

Cautions with other medicines

Some medicines and cetirizine interfere with each other and increase the chances of you having side effects. Check with your pharmacist or doctor if you’re taking:

• midodrine, a medicine used to treat low blood pressure
• ritonavir, a medicine used to treat HIV infection
• any medicine that makes you drowsy, gives you a dry mouth, or makes it difficult for you to pee. Taking cetirizine might make these side effects worse.

Mixing cetirizine with herbal remedies and supplements

There might be a problem taking some herbal remedies and supplements alongside cetirizine – especially ones that cause sleepiness, a dry mouth or make it difficult to urinate.

Ask your pharmacist for advice.

What is cetirizine used for

Cetirizine is used to treat hay fever (allergy to pollen, dust, or other substances in the air) and allergy to other substances (such as dust mites, animal dander, cockroaches, and molds) or allergy symptoms such as allergic conjunctivitis (red, itchy eye), eczema and hives. Cetirizine is also used for reactions to insect bites and stings and for some food allergies and the symptoms of common cold. These symptoms include sneezing; runny nose; itchy, red, watery eyes; and itchy nose or throat. Cetirizine is also used to treat itching and redness caused by hives. However, cetirizine does not prevent hives or other allergic skin reactions.

Cetirizine is also available in combination with pseudoephedrine (Sudafed, others). If you are taking the cetirizine and pseudoephedrine combination product, read the information on the package label or ask your doctor or pharmacist for more information.

• Do NOT use cetirizine to treat hives that are bruised or blistered, that are an unusual color, or that do not itch. Call your doctor if you have these types of hives.

Cetirizine may be prescribed for other uses; ask your doctor or pharmacist for more information.

Stop taking cetirizine and see your doctor if your hives do not improve during the first 3 days of your treatment or if your hives last longer than 6 weeks. If you do not know the cause of your hives, see your doctor.

If you are taking cetirizine to treat hives, and you develop any of the following symptoms, get emergency medical help right away:

• difficulty swallowing, speaking, or breathing;
• swelling in and around the mouth or swelling of the tongue;
• wheezing; drooling; dizziness; or loss of consciousness.

These may be symptoms of a life-threatening allergic reaction called anaphylaxis. If your doctor suspects that you may experience anaphylaxis with your hives, he may prescribe an epinephrine injector (EpiPen). Do not use cetirizine in place of the epinephrine injector.

Cetirizine dosage

Usual Adult Dose for Allergic Rhinitis

• 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Some experts recommend: Patients over 65 years of age should start with 5 mg orally once a day.

Uses:

• Relief of symptoms associated with perennial allergic rhinitis due to allergens (e.g., sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, tearing)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Usual Adult Dose for Urticaria

• 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Some experts recommend: Patients over 65 years of age should start with 5 mg orally once a day.

Uses:

• Relief of symptoms associated with perennial allergic rhinitis due to allergens (e.g., sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, tearing)
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria

Usual Pediatric Dose for Allergic Rhinitis

6 months to 2 years:

• Initial dose: 2.5 mg orally once a day
• Maintenance dose: 2.5 mg orally once to 2 times a day
• Maximum dose: 5 mg/day

2 to 5 years:

• Initial dose: 2.5 mg orally once a day
• Maintenance dose: 2.5 mg orally 2 times a day OR 5 mg orally once a day
• Maximum dose: 5 mg/day

6 years and older:

• 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Uses:

• Relief of symptoms associated with perennial allergic rhinitis due to allergens (e.g., sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, tearing) in patients 2 years and older
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in patients 6 months and older

Usual Pediatric Dose for Urticaria

6 months to 2 years:

• Initial dose: 2.5 mg orally once a day
• Maintenance dose: 2.5 mg orally once to 2 times a day
• Maximum dose: 5 mg/day

2 to 5 years:

• Initial dose: 2.5 mg orally once a day
• Maintenance dose: 2.5 mg orally 2 times a day OR 5 mg orally once a day
• Maximum dose: 5 mg/day

6 years and older:

• 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Uses:

• Relief of symptoms associated with perennial allergic rhinitis due to allergens (e.g., sneezing, rhinorrhea, postnasal discharge, nasal pruritus, ocular pruritus, tearing) in patients 2 years and older
• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in patients 6 months and older

Renal Dose Adjustments

In patients 12 years of age and older with decreased renal function (creatinine clearance 11–31 mL/min), patients on hemodialysis (creatinine clearance less than 7 mL/min), and in hepatically impaired patients, a dose of 5 mg once daily is recommended. Similarly, pediatric patients aged 6 to 11 years with impaired renal or hepatic function should use the lower recommended dose. Because of the difficulty in reliably administering doses of less than 2.5 mg (½ teaspoon) of cetirizine syrup and in the absence of pharmacokinetic and safety information for cetirizine in children below the age of 6 years with impaired renal or hepatic function, its use in this impaired patient population is not recommended.

Liver Dose Adjustments

In patients 12 years of age and older with decreased renal function (creatinine clearance 11–31 mL/min), patients on hemodialysis (creatinine clearance less than 7 mL/min), and in hepatically impaired patients, a dose of 5 mg once daily is recommended. Similarly, pediatric patients aged 6 to 11 years with impaired renal or hepatic function should use the lower recommended dose. Because of the difficulty in reliably administering doses of less than 2.5 mg (½ teaspoon) of cetirizine syrup and in the absence of pharmacokinetic and safety information for cetirizine in children below the age of 6 years with impaired renal or hepatic function, its use in this impaired patient population is not recommended.

Dialysis

Data not available

Cetirizine dosing information

Cetirizine Adult Dosage

Usual Adult Dose for Allergic Rhinitis

• 5 to 10 mg orally or chewed once a day

Usual Adult Dose for Urticaria

• 5 to 10 mg orally or chewed once a day

Adults 65 years and over

• 5 mg once a day; do not take more than 5 mg in 24 hours.

Cetirizine Children Dosage

Cetirizine is usually given once or twice each day.

• Once a day: it can be given in the morning or the evening.
• Twice a day: give once in the morning and once in the evening. Ideally, these times are 10–12 hours apart, for example some time between 7 and 8 am, and between 7 and 8 pm.

Give the medicine at about the same time(s) each day so that this becomes part of your child’s daily routine, which will help you to remember.

Usual Pediatric Dose for Allergic Rhinitis:

• 6 months to 2 years: 2.5 mg orally once a day, 12 months and older may be increased to 2.5 mg orally twice a day.
• 2 to 5 years: 2.5 mg orally once a day, may be increased to 5 mg/day in 1 to 2 divided doses.
• 6 years or older: 5 to 10 mg orally or chewed once a day.

Usual Pediatric Dose for Urticaria:

• 6 months to 2 years: 2.5 mg orally once a day, 12 months and older may be increased to 2.5 mg orally twice a day.
• 2 to 5 years: 2.5 mg orally once a day, may be increased to 5 mg/day in 1 to 2 divided doses.
• 6 years or older: 5 to 10 mg orally or chewed once a day.

What if my child is sick (vomits)?

• If your child is sick less than 30 minutes after having a dose of cetirizine, give them the same dose again.
• If your child is sick more than 30 minutes after having a dose of cetirizine, you do not need to give them another dose. Wait until the next normal dose.

If your child is sick again, seek advice from your doctor, pharmacist or hospital. They will decide what to do based on your child’s condition and the specific medicine involved.

What if I forget to give it?

If you normally give it once a day in the morning

• Give the missed dose when you remember during the day.

If you normally give it once a day in the evening

• If you remember before bedtime, give the missed dose. If you remember after this, you do not need to wake your child up to give them the missed dose. You can give the missed dose in the morning.

If you normally give it twice a day

• If you remember up to 4 hours after you should have given a dose, give your child the missed dose. For example, if you usually give a dose at about 7 am, you can give the missed dose at any time up to 11 am. If you remember after that time, do not give the missed dose. Wait until the next normal dose.

How to take cetirizine

You can take cetirizine with or without food.

Always take cetirizine tablets or capsules with a drink of water, milk or juice. Swallow them whole. Do not chew them.

Cetirizine liquid may be easier for children to take than tablets or capsules. The liquid medicine will come with a plastic syringe or spoon to help you measure out the right dose. If you don’t have a syringe or spoon, ask your pharmacist for one. Do not use a kitchen teaspoon as it will not give the right amount.

When to take cetirizine

You may only need to take cetirizine on a day you have symptoms, such as if you’ve been exposed to a trigger like animal hair. Or you may need to take it regularly to prevent symptoms, such as to stop hay fever during spring and summer.

What if I forget to take cetirizine?

Take your forgotten dose as soon as you remember, unless it is nearly time for your next dose. Do not take a double dose to make up for a forgotten dose.

If you forget to give a dose to a child who is taking cetirizine twice a day, you can give the dose if it’s within 4 hours of when they should have had it. If you remember more than 4 hours after, do not give the missed dose. Instead, wait until the next dose and carry on as normal.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much cetirizine?

Cetirizine is generally very safe. Taking too much is unlikely to harm you or your child.

If you take an extra dose by mistake, you might get some of the common side effects. If this happens or you’re concerned, contact your doctor.

Can I take cetirizine at higher doses than on the packet?

Your doctor might suggest you or your child take a higher dose of cetirizine (up to 4 times the usual dose) for severe itchy skin rash or angioedema (swelling underneath the skin).

Taking high doses of cetirizine isn’t suitable for everyone though. Speak to your doctor if you think cetirizine isn’t working for you.

Cetirizine side effects

Like all medicines, cetirizine can cause side effects although not everyone gets them.

The most commonly reported side effects include somnolence, dizziness, and headache.

Common side effects

Common side effects of cetirizine happen in more than 1 in 100 people. Talk to your doctor or pharmacist if these side effects bother you or don’t go away:

• feeling sleepy and tired
• drowsiness
• excessive tiredness
• headache
• dry mouth
• feeling sick or dizzy
• stomach pain
• diarrhea
• vomiting
• sore throat
• cold-like symptoms of the nose
• itch or rash
• tingling in the hands and feet
• feeling agitated

Children are more likely to get diarrhea or cold-like symptoms of the nose than adults.

Nervous system

• Very common (10% or more): Somnolence (up to 14.3%), headache (up to 14%)
• Common (1% to 10%): Dizziness
• Frequency not reported: Altered sense of taste, paresthesia, hypertonia, tremor, abnormal coordination/incoordination, ataxia, hyperesthesia, hyperkinesia, hypoesthesia, migraine, paralysis, twitching, parosmia, taste loss/perversion
• Postmarketing reports: Convulsions, dysgeusia, dyskinesia, dystonia, syncope, amnesia, vertigo, memory impairment

Gastrointestinal

• Common (1% to 10%): Dry mouth, nausea, diarrhea, vomiting, abdominal pain
• Uncommon (0.1% to 1%): Dyspepsia
• Frequency not reported: Tongue disorder, constipation, flatulence, increased salivation, aggravated tooth caries, eructation, gastritis, hemorrhoids, melena, rectal hemorrhage, stomatitis/ulcerative stomatitis, tongue discoloration/edema, enlarged abdomen

Respiratory

• Common (1% to 10%): Pharyngitis, rhinitis, coughing, epistaxis
• Frequency not reported: Dyspnea, respiratory disorder, bronchospasm, upper respiratory tract infection, dysphonia, bronchitis, hyperventilation, increased sputum, pneumonia, sinusitis, nasal polyp

Other

• Common (1% to 10%): Fatigue
• Frequency not reported: Earache, tinnitus, fever, pain, rigor, thirst, deafness, ototoxicity, accidental injury, face edema, leg edema, malaise
• Postmarketing reports: Asthenia, stillbirth

Psychiatric

• Common (1% to 10%): Insomnia
• Frequency not reported: Nervousness, impaired concentration, confusion, decreased libido, abnormal thinking, anxiety, depersonalization, emotional lability, euphoria, paroniria, sleep disorder
• Postmarketing reports: Agitation, aggression/aggressive reaction, depression, hallucination, tic, suicidal ideation/suicide

Musculoskeletal

• Very rare (less than 0.01%): Myelitis
• Frequency not reported: Back pain, myalgia, arthralgia, bone disorder/fracture, leg cramps, arthritis, arthrosis, muscle weakness

Dermatologic

• Frequency not reported: Pruritus/intense itching, increased sweating, acne, alopecia, bullous eruption, dermatitis, dry skin, eczema, erythematous rash, furunculosis, hyperkeratosis, hypertrichosis, maculopapular rash, photosensitivity/photosensitivity toxic reaction, purpura, seborrhea, skin disorder/nodule
• Postmarketing reports: Rash, urticaria, angioneurotic edema, fixed drug eruption, acute generalized exanthematous pustulosis

Ocular

• Frequency not reported: Eye abnormality, periorbital edema, abnormal vision, eye pain, conjunctivitis, ptosis, visual field defects, blindness, glaucoma, ocular hemorrhage, xerophthalmia, periorbital edema/eye swelling
• Postmarketing reports: Accommodation disorder/loss of accommodation, blurred vision, oculogyration, orofacial dyskinesia

Genitourinary

• Frequency not reported: Polyuria, urinary retention, urinary tract infection, dysmenorrhea, hematuria, micturition frequency, urinary incontinence, female breast pain, intermenstrual bleeding, leukorrhea, menorrhagia, vaginitis
• Postmarketing reports: Dysuria, enuresis

Cardiovascular

• Frequency not reported: Flushing, palpitations, tachycardia, edema/general edema, chest pain, cardiac failure, hypertension, hot flashes, peripheral edema, pallor
• Postmarketing reports: Severe hypotension

Metabolic

• Frequency not reported: Increased appetite, anorexia, increased weight, dehydration, diabetes mellitus

Hepatic

• Frequency not reported: Reversible transaminase elevations
• Postmarketing reports: Abnormal hepatic function (increased transaminases, alkaline phosphatase, GGT, bilirubin), cholestasis, hepatitis

Hypersensitivity

• Frequency not reported: Allergic reactions/delayed allergic reactions
• Postmarketing reports: Hypersensitivity, anaphylactic shock

Hematologic

• Frequency not reported: Lymphadenopathy
• Postmarketing reports: Thrombocytopenia, hemolytic anemia

Renal

• Frequency not reported: Cystitis
• Postmarketing reports: Glomerulonephritis

Serious side effects

It’s rare to have a serious side effect with cetirizine.

Tell your doctor straight away if you have:

• bruising or bleeding that’s more than normal
• difficulty breathing or swallowing

Cetirizine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction to cetirizine. A serious allergic reaction is an emergency. Contact a doctor straight away if you think you or someone around you is having a serious allergic reaction.

The warning signs of a serious allergic reaction are:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• wheezing
• tightness in the chest or throat
• having trouble breathing or talking
• swelling of the mouth, face, lips, tongue, or throat

These are not all the side effects of cetirizine. For a full list see the leaflet inside your medicines packet.

How to cope with side effects

What to do about:

• feeling sleepy – try a different non-drowsy antihistamine. If this doesn’t help, talk to your doctor.
• feeling sick – stick to simple meals and don’t eat rich or spicy food
• headache – take an everyday painkiller like paracetamol or ibuprofen
• dry mouth – chew sugar-free gum or suck sugar-free sweets
• diarrhea – drink plenty of water in small, frequent sips. It may also help to take oral rehydration solutions like pedialyte. You can buy these from a pharmacy or supermarket to prevent dehydration. Don’t take any other medicines to treat diarrhea without speaking to a pharmacist or a doctor.

Human Toxicity Reports

In a controlled study of 1 week’s duration in patients 6-11 months of age, those receiving cetirizine exhibited greater irritability/fussiness than those receiving placebo. In a controlled study in patients 12 months of age and older, insomnia occurred more frequently with cetirizine than with placebo (9 vs 5.3%, respectively). In those who received 5 mg or more daily, fatigue occurred in 3.6 or 1.3% and malaise in 3.5 or 1.8% of those receiving cetirizine or placebo, respectively ³.

Fatigue or dizziness occurred in 5.9 or 2%, respectively, of patients 12 years of age and older receiving cetirizine, whereas these effects occurred in 2.6 or 1.2%, respectively, of patients receiving placebo ⁴. Headache was reported in more than 2% of patients 12 years of age and older receiving the drug; however, headache occurred more frequently in patients receiving placebo. In clinical trials in patients 6-11 years of age, headache occurred in 11, 14, or 12.3% of patients receiving 5-mg doses, 10-mg doses, or placebo, respectively. Abnormal coordination, ataxia, confusion, abnormal thinking, agitation, amnesia, anxiety, depersonalization, depression, emotional lability, euphoria, impaired concentration, insomnia, sleep disorders, nervousness, paroniria, dysphonia, asthenia, malaise, pain, hyperesthesia, hypoesthesia, hyperkinesia, hypertonia, migraine headache, myelitis, paralysis, paresthesia, ptosis, syncope, tremor, twitching, and vertigo have been reported in less than 2% of patients 12 years of age and older and children 6-11 years of age receiving cetirizine hydrochloride; however, a causal relationship to the drug has not been established. Aggressive reaction, seizures, hallucinations, suicidal ideation, and suicide have been reported rarely during postmarketing surveillance ⁴.

The most frequent adverse effect in patients 12 years of age and older reported during cetirizine therapy is somnolence, occurring in 11, 14, or 6% of patients receiving 5-mg doses, 10-mg doses, or placebo, respectively ⁴. Overall, somnolence has been reported in 13.7 or 6.3% of patients receiving cetirizine or placebo, respectively. In addition, in clinical trials in patients 6-11 years of age, somnolence occurred in 1.9, 4.2, or 1.3% of patients receiving 5-mg doses, 10-mg doses, or placebo, respectively. Discontinuance of therapy because of somnolence has been reported in 1 or 0.6% of patients receiving cetirizine or placebo, respectively.1 3 In patients 6-24 months of age, somnolence occurred with essentially the same frequency in those who received cetirizine versus placebo.

Adverse effects reported in 1% or more of patients 12 years of age and older with seasonal allergic rhinitis who received extended-release tablets of cetirizine hydrochloride in fixed combination with pseudoephedrine hydrochloride (Zyrtec-D) included insomnia, dry mouth, fatigue, somnolence, pharyngitis, epistaxis, accidental injury, dizziness, and sinusitis ⁴.

A case of recurrent acute hepatitis related to the use of cetirizine has been described in a 26-year-old man who was hospitalized with a week-long history of weakness, nausea, anorexia, and hyperchromic urine, which had developed after 6 days of therapy with oral cetirizine 10 mg/day for allergic rhinitis ⁵. Admission laboratory testing revealed evidence of acute hepatitis and seropositivity for liver-kidney microsome antibodies. Liver biopsy findings of diffuse portal tract and lobular inflammation with a prominent eosinophilic infiltrate were consistent with drug-related hepatitis. The patient was discharged after one week of treatment with tocopherol and glutathione. Three months after discharge, transaminase levels were normal. At 6 months, seropositivity for liver-kidney microsome antibodies was still present, but considerably less intense. The patient had suffered 2 previous episodes of “acute hepatitis of unknown origin,” and both had occurred after cetirizine use ⁵. The study authors indicated cetirizine as the probable cause of acute hepatitis, and the positivity for liver-kidney microsome antibodies is suggestive of an autoimmune mechanism for liver damage. This is the fourth reported case of acute hepatitis associated with cetirizine and the second in which liver-kidney microsome antibodies have been documented. Although cetirizine is considered to have low potential for severe hepatic toxicity, the possibility that it can provoke autoimmune-mediated hepatotoxicity should be considered ⁵.

In U.S. clinical trials, transient reversible hepatic transaminase elevations were observed in <2% of patients during cetirizine therapy ⁶. A case of cetirizine-induced cholestasis in a 28-year-old man with no previous hepatobiliary disease after a 2-year period of taking cetirizine on a daily basis is reported. The treatment of this patient included the use of ursodeoxycholic acid, as well as hydroxyzine, for symptomatic relief of pruritus. In light of the patient’s clinical and biochemical improvement while using hydroxyzine, it appears that the hepatic metabolism of hydroxyzine to metabolites, including cetirizine, is involved in the pathogenesis of this particular case of drug-induced hepatotoxicity. Cetirizine should be considered as a potential cause of drug-induced cholestasis ⁶.

The case of a 29-yr-old woman with pruritus sine materiae who was receiving treatment with oral tablets of 20 mg of cetirizine hydrochloride daily, after which she developed generalized chronic urticaria associated with cetirizine administration is presented ⁷. The patient was admitted for diagnostic purposes, and cetirizine was stopped on admission. Surprisingly, the patient’s urticarial lesions resolved completely within 4 days. Subsequently, the patient showed a pseudoallergic response to a cellular antigen stimulation test performed with cetirizine. The patient was rechallenged with cetirizine 7 wk after discharge. The patient developed a generalized wheal reaction 15 min after an oral dose of 5 mg of cetirizine ⁷.

Dystonia is a movement disorder that causes involuntary contractions of the muscles. Dystonia can affect just one muscle, a group of muscles, or all of the muscles. The most common cause of acquired dystonia in childhood is drugs. Cetirizine is widely used for allergic disorders in childhood. It is without central nervous system side effects at recommended dosages. A case of cetirizine-induced acute acquired dystonia whose symptoms completely resolved after the discontinuation of the drug is reported ⁸.

Cetirizine can cause oculogyric crisis, especially in the pediatric age group according to a retrospective, observational case series and case reports that were collected from the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon) ⁹.

Cetirizine overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Symptoms of cetirizine overdose may include:

• restlessness
• irritability
• drowsiness

A case of a 18-year-old female with the history of anorexia for 2 years, who was admitted to a Clinic of Toxicology because of suicidal attempt with use of cetirizine is presented ¹⁰. The laboratory results revealed metabolic acidosis with the pH 7.13; pO2 88 mm Hg; pCO2 36 mm Hg; HCO3 12.0 mmol/L; BE (-)17 mmol/L; SO2 100% and hypokalemia (K+ 3.1 mmol/L). On physical examination blood pressure was 70/40 mm Hg, heart rate was 36-40 beats/min. Convulsions were observed. After about two hours of intensive treatment there was a cardiac arrest in the form of ventricular fibrillation. The resuscitation procedures which lasted for over 2.5 hours were ineffective ¹⁰.. The high dose (270 mg) of cetirizine as well as anorexia and hypokalemia could have been the cause of the unique character of the symptoms in this case. Further investigations should be carried out to confirm the safety of cetirizine in the conditions of massive intoxication and with coexistence of other risk factors ¹⁰.

In one adult patient who took 150 mg of cetirizine, the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdose of cetirizine (approximately 180 mg), restlessness and irritability were observed initially; this was followed by drowsiness ¹¹.

Few reports exist on the result of cetirizine overdose in children ¹². A case report of a 12 fold overdose of cetirizine in a four-year-old-boy (weight 20 kg) who accidentally ingested 60 mg. Vomiting was induced 1 1/2 hour after ingestion in the out-patient clinic at the local hospital because of severe drowsiness. Due to continued lethargy he was transferred to the referral pediatric department for further observation. He was fully recovered after five to six hours without any treatment ¹². Electrocardiographic monitoring was normal. Five incidents of cetirizine overdose in children have been reported previously. Drowsiness and sedation were observed, but no other side effects ¹². The risk of cardiac events related to an overdose of cetirizine is extremely small. A certain degree of sedation is to be expected.

A cardiac condition called Torsades de pointes has been associated hypokalemia. A case of a dialysed patient with chronic renal failure who had symptomatic episodes of torsades de pointes in the context of hypokalemia and cetirizine overdose has been described ¹³.

References

1. Handing KB, Shabalin IG, Szlachta K, Majorek KA, Minor W. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug-binding site. Molecular immunology. 2016;71:143-151. doi:10.1016/j.molimm.2016.02.003. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800003/
2. Weber-Schoendorfer C, Schaefer C; Reprod Toxicol 26 (1): 19-23 (2008). https://www.sciencedirect.com/science/article/pii/S0890623808001238
3. American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 27-8
4. American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 27
5. Pompili M et al; Ann Pharmacother 38 (11): 1844-7 (2004). Available from, as of July 24, 2009 https://www.ncbi.nlm.nih.gov/pubmed/15383643
6. Fong DG et al; J Clin Gastroenterol 31 (3): 250-3 (2000). Available from, as of July 6, 2009 https://www.ncbi.nlm.nih.gov/pubmed/11034010
7. Karamfilov T et al; Br J Dermatol 140 (5): 979-80; 1999 https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2133.1999.02849.x
8. Esen I et al; Pediatr Emerg Care 24 (9): 627-8 (2008). Available from, as of July 10, 2009 https://www.ncbi.nlm.nih.gov/pubmed/18797375
9. Fraunfelder FW, Fraunfelder FT; Am J Ophthalmol 137 (2): 355-7;2004 https://www.ncbi.nlm.nih.gov/pubmed/14962433
10. Chodorowski Z et al; Przegl Lek 61 (4): 433-4 (2004). Available from, as of July 6, 2009 https://www.ncbi.nlm.nih.gov/pubmed/15521622
11. US Natl Inst Health; DailyMed. Current Medication Information for Zyrtec – cetirizine hydrochloride https://dailymed.nlm.nih.gov/dailymed/index.cfm
12. Hansen JJ et al; Ugeskr Laeger 160 (41): 5946-7 (1998). Available from, as of July 24, 2009 https://www.ncbi.nlm.nih.gov/pubmed/9786037
13. Renard S et al; Arch Mal Coeur Vaiss 98 (2): 157-61 (2005). Available from, as of July 24, 2009 https://www.ncbi.nlm.nih.gov/pubmed/15787309

What is sodium bicarbonate

Sodium bicarbonate (NaHCO₃), also known as baking soda, is used to relieve heartburn, sour stomach, or acid indigestion by neutralizing excess stomach acid. When used for this purpose, sodium bicarbonate is said to belong to the group of medicines called antacids. Sodium bicarbonate may be used to treat the symptoms of stomach or duodenal ulcers. Sodium bicarbonate is also used to make the blood and urine more alkaline in certain conditions.

Sodium bicarbonate is a white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. Sodium bicarbonate is the monosodium salt of carbonic acid with alkalinizing and electrolyte replacement properties. Slightly alkaline (bitter) taste, pH (of freshly prepared 0.1 molar aqueous solution): 8.3 at 77 °F and pH (of saturated solution): 8-9. Sodium bicarbonate in water dissociates to provide sodium (Na⁺) and bicarbonate (HCO3¯ ) ions. Sodium (Na⁺) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Bicarbonate (HCO3¯ ) is a normal constituent of body fluids and the normal plasma level ranges from 24 to 31 mEq/liter. Ion formation increases plasma bicarbonate and buffers excess hydrogen ion concentration, resulting in raised blood pH. Plasma concentration is regulated by the kidney through acidification of the urine when there is a deficit or by alkalinization of the urine when there is an excess. Bicarbonate anion is considered “labile” since at a proper concentration of hydrogen ion (H⁺) it may be converted to carbonic acid (H2CO3) and thence to its volatile form, carbon dioxide (CO2) excreted by the lung. Normally a ratio of 1:20 (carbonic acid; bicarbonate) is present in the extracellular fluid. In a healthy adult with normal kidney function, practically all the glomerular filtered bicarbonate ion is reabsorbed; less than 1% is excreted in the urine.

Sodium bicarbonate should not be given to young children (up to 6 years of age) unless prescribed by their doctor. Since children cannot usually describe their symptoms very well, a doctor should check the child before giving sodium bicarbonate. The child may have a condition that needs other treatment. If so, sodium bicarbonate will not help and may even cause unwanted effects or make the condition worse.

Sodium bicarbonate for oral use is available without a prescription.

This product is available in the following dosage forms:

• Tablet
• Solution
• Powder
• Granule
• Capsule

Storage

Store sodium bicarbonate medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Taking sodium bicarbonate with food, alcohol and other medicines

It’s best to take sodium bicarbonate with food or soon after eating because this is when you’re most likely to get indigestion or heartburn.

The effect of sodium bicarbonate medicine may also last longer if taken with food.

Sodium bicarbonate can affect how well other medicines work, so don’t take other medicines within two to four hours of taking an antacid (see Drug Interactions below).

You can drink alcohol while taking sodium bicarbonate, but alcohol can irritate your stomach and make your symptoms worse.

Precautions

If this medicine has been ordered by your doctor and if you will be taking it regularly for a long time, your doctor should check your progress at regular visits. This is to make sure the medicine does not cause unwanted effects.

Sodium bicarbonate is contraindicated in patients with chloride loss from vomiting or from continuous gastrointestinal suction, who are receiving diuretics that are known to produce a hypochloremic alkalosis, with metabolic or respiratory alkalosis, with hypocalcemia in which alkalosis may produce tetany, hypertension, convulsions or congestive heart failure, and in patients in whom the administration of sodium would be clinically detrimental.

Do not take sodium bicarbonate:

• Within 1 to 2 hours of taking other medicine by mouth. To do so may keep the other medicine from working properly.
• For a long period of time. To do so may increase the chance of side effects.

For patients on a sodium-restricted diet:

Sodium bicarbonate contains a large amount of sodium. If you have any questions about this, check with your health care professional.

For patients taking sodium bicarbonate as an antacid:

• Do not take sodium bicarbonate medicine if you have any signs of appendicitis (such as stomach or lower abdominal pain, cramping, bloating, soreness,
• nausea, or vomiting). Instead, check with your doctor as soon as possible.
• Do not take sodium bicarbonate with large amounts of milk or milk products. To do so may increase the chance of side effects.
• Do not take sodium bicarbonate for more than 2 weeks or if the problem comes back often. Instead, check with your doctor. Antacids should be used only for occasional relief, unless otherwise directed by your doctor.

Serum bicarbonate

Bicarbonate (HCO₃⁻, sometimes reported as total CO₂) is an electrolyte, a negatively charged ion that is used by the body to help maintain the body’s acid-base (pH) balance. It also works with the other electrolytes (sodium, potassium, and chloride) to maintain electrical neutrality at the cellular level. This test measures the total amount of carbon dioxide (CO2) in the blood, which occurs mostly in the form of bicarbonate (HCO3-). The CO₂ is mainly a by-product of various metabolic processes.

The lungs provide oxygen and regulate CO2. The CO2 is produced by the body and is in balance with bicarbonate bicarbonate (HCO₃⁻). The overall balance of these chemicals is an indication of the functional well-being of several basic body functions. They are important in maintaining a wide range of body functions, including heart and skeletal muscle contraction and nerve impulse conduction.

Sodium, along with other electrolytes such as potassium, chloride, and bicarbonate (or total CO₂), helps cells function normally and helps regulate the amount of fluid in the body. While sodium is present in all body fluids, it is found in the highest concentration in the blood and in the fluid outside of the body’s cells. This extracellular sodium, as well as all body water, is regulated by the kidneys.

Measuring bicarbonate as part of an electrolyte or metabolic panel may help diagnose an electrolyte imbalance or acidosis or alkalosis. Acidosis and alkalosis describe the abnormal conditions that result from an imbalance in the pH of the blood caused by an excess of acid or alkali (base). This imbalance is typically caused by some underlying condition or disease.

The body’s maintenance of a healthy pH range for blood and tissues that is slightly basic (pH between 7.35 – 7.45). This balance is achieved through the use of systems in the blood (which help to minimize pH changes) and by the lungs and kidneys, which eliminate excess amounts of acids or bases from the body.

The lungs and kidneys are the major organs involved in regulating blood pH through the removal of excess bicarbonate.

• The lungs flush acid out of the body by exhaling CO₂. Raising and lowering the respiratory rate alters the amount of CO₂ that is breathed out, and this can affect blood pH within minutes.
• The kidneys eliminate acids in the urine and they regulate the concentration of bicarbonate (HCO₃⁻, a base) in blood. Acid-base changes due to increases or decreases in HCO₃⁻ concentration occur more slowly than changes in CO₂, taking hours or days.

Any disease or condition that affects the lungs, kidneys, metabolism, or breathing has the potential to cause acidosis or alkalosis.

The bicarbonate test gives a healthcare practitioner a rough estimate of a patient’s acid-base balance. This is usually sufficient, but measurements of gases dissolved in the blood (blood gases) may be done if more information is needed. Bicarbonate is typically measured along with sodium, potassium, and possibly chloride in an electrolyte panel as it is the balance of these molecules that gives the healthcare practitioner the most information.

The bicarbonate (or total CO₂) test is usually ordered along with sodium, potassium, and chloride as part of an electrolyte panel. The electrolyte panel is used to help detect, evaluate, and monitor electrolyte imbalances and/or acid-base (pH) imbalances (acidosis or alkalosis). It may be ordered as part of a routine exam or to help evaluate a variety of chronic or acute illnesses.

This testing may be ordered when acidosis or alkalosis is suspected or when someone has an acute condition with symptoms that may include the following:

• Prolonged vomiting and/or diarrhea
• Weakness, fatigue
• Difficulty breathing (respiratory distress)

Electrolytes may be ordered at regular intervals when a person has a disease or condition or is taking a medication that can cause an electrolyte imbalance. Electrolyte panels or basic metabolic panels are commonly used to monitor treatment of certain problems, including high blood pressure (hypertension), heart failure, and liver and kidney disease.

An electrolyte panel may be used to help monitor conditions, such as kidney disease, lung disorders, and high blood pressure (hypertension). When acidosis or alkalosis is identified, bicarbonate (as part of the electrolyte panel) and blood gases may be ordered to evaluate the severity of the pH imbalance. These tests help determine whether it is primarily respiratory (due to an imbalance between the amount of oxygen coming in and CO₂ being released) or metabolic (due to increased or decreased amounts of bicarbonate in the blood). They also help monitor treatment until acid-base balance is restored.

What does the test bicarbonate result mean?

When bicarbonate levels are higher or lower than normal, it suggests that the body is having trouble maintaining its acid-base balance, either by failing to remove carbon dioxide through the lungs or the kidneys or perhaps because of an electrolyte imbalance, particularly a deficiency of potassium. Both of these imbalances may be due to a wide range of conditions.

Examples of causes of a low bicarbonate level include:

• Addison disease
• Chronic diarrhea
• Diabetic ketoacidosis
• Metabolic acidosis
• Respiratory alkalosis, which can be caused by hyperventilation
• Shock
• Kidney disease
• Ethylene glycol or methanol poisoning
• Salicylate (aspirin) overdose
• Drugs that may decrease bicarbonate levels include methicillin, nitrofurantoin, tetracycline, thiazide diuretics, and triamterene.

Examples of causes of a high bicarbonate level include:

• Severe, prolonged vomiting and/or diarrhea
• Lung diseases, including COPD
• Cushing syndrome
• Conn syndrome
• Metabolic alkalosis
• Some drugs may increase bicarbonate levels including fludrocortisone, barbiturates, bicarbonates, hydrocortisone, loop diuretics, and steroids.

If bicarbonate levels are too high or low, what treatments can help?

If your bicarbonate is high or low, your healthcare practitioner will identify and treat the underlying cause. For example, high bicarbonate may be caused by emphysema, which may be treated with oxygen therapy and medications, or by severe diarrhea or vomiting, which would be addressed by treating the cause of the diarrhea or vomiting. Low bicarbonate may be caused by diabetic ketoacidosis, for example, which can be addressed in part by fluid and electrolyte replacement and insulin therapy.

If I’ve had a bicarbonate (total CO₂) test, why does my doctor want to test my blood gases?

Blood gas tests, in which blood is drawn from an artery instead of a vein, can give your healthcare practitioner more information about your acid-base balance. They can tell your provider whether your lungs are working properly to keep oxygen and carbon dioxide at healthy levels.

Sodium bicarbonate injection

Sodium Bicarbonate Injection is a sterile, nonpyrogenic, hypertonic solution of Sodium Bicarbonate (NaHCO₃) in water for injection for administration by the intravenous route as an electrolyte replenisher and systemic alkalizer.

Solution is offered in 8.4% concentration. The solution has an approximate pH of 8.0 (7.5 to 8.5). Carbon dioxide may have been added to adjust the pH of the solution to approximately 8.0.

How is sodium bicarbonate injection supplied

Sodium Bicarbonate Injection, USP is supplied in the following dosage form.

In 50 mL single-dose packages containing a Luer-Jet™ Luer-Lock Prefilled Syringe.

10 individual cartons shrink wrapped as a group of 10 cartons.

Stock No.	NDC No.	Dosage Form	Con. %	mg/mL (NaHCO3)	mEq/mL (Na+)	mEq/mL (HCO3–)	mEq/Contain- er size (mL)	mOsm/ mL
3352	76329-3352-1	Prefilled Syringe	8.4%	84	1	1	50/50	2

The solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only for use as a single-dose injection. When smaller doses are required, the unused portion should be discarded with the entire unit.

Sodium Bicarbonate, 84 mg is equal to one milliequivalent each of sodium (Na⁺) and bicarbonate (HCO3¯ ) . Sodium Bicarbonate, USP is chemically designated NaHCO₃, a white crystalline powder soluble in water. Water for Injection, USP is chemically designated H2O.

Sodium Bicarbonate Injection- Clinical Pharmacology

Intravenous Sodium Bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis.

Indications and Usage for Sodium Bicarbonate Injection

Sodium Bicarbonate Injection, USP is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis. Sodium Bicarbonate is further indicated in the treatment of certain drug intoxications, including barbiturates (where dissociation of the barbiturate-protein complex is desired), in poisoning by salicylates or methyl alcohol and in hemolytic reactions requiring alkalinization of the urine to diminish nephrotoxicity of hemoglobin and its breakdown products. Sodium Bicarbonate also is indicated in severe diarrhea which is often accompanied by a significant loss of bicarbonate.

Treatment of metabolic acidosis should, if possible, be superimposed on measures designed to control the basic cause of the acidosis – e.g., insulin in uncomplicated diabetes, blood volume restoration in shock. But since an appreciable time interval may elapse before all of the ancillary effects are brought about, bicarbonate therapy is indicated to minimize risks inherent to the acidosis itself.

Vigorous bicarbonate therapy is required in any form of metabolic acidosis where a rapid increase in plasma total CO2 content is crucial – e.g., cardiac arrest, circulatory insufficiency due to shock or severe dehydration, and in severe primary lactic acidosis or severe diabetic acidosis.

Sodium Bicarbonate Injection Contraindications

Sodium Bicarbonate Injection, USP is contraindicated in patients who are losing chloride by vomiting or from continuous gastrointestinal suction, and in patients receiving diuretics known to produce a hypochloremic alkalosis.

Sodium Bicarbonate Injection Warnings

Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.

In patients with diminished renal function, administration of solutions containing sodium ions may result in sodium retention.

The intravenous administration of these solutions can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema.

Sodium Bicarbonate Injection Precautions

General

Do not use unless solution is clear and the container or seal is intact. Discard unused portion.

The potentially large loads of sodium given with bicarbonate require that caution be exercised in the use of Sodium Bicarbonate in patients with congestive heart failure or other edematous or sodium-retaining states, as well as in patients with oliguria or anuria.

Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin.

Potassium depletion may predispose to metabolic alkalosis and coexistent hypocalcemia may be associated with carpopedal spasm as the plasma pH rises. These dangers can be minimized if such electrolyte imbalances are appropriately treated prior to or concomitantly with bicarbonate infusion.

Laboratory Tests

The aim of all bicarbonate therapy is to produce a substantial correction of the low total CO2 content and blood pH, but the risks of overdosage and alkalosis should be avoided. Hence, repeated fractional doses and periodic monitoring by appropriate laboratory tests are recommended to minimize the possibility of overdosage.

Sodium Bicarbonate Injection Drug Interactions

Additives may be incompatible; norepinephrine and dobutamine are incompatible with Sodium Bicarbonate solution.

The addition of Sodium Bicarbonate to parenteral solutions containing calcium should be avoided, except where compatibility has been previously established. Precipitation or haze may result from Sodium Bicarbonate/calcium admixtures. NOTE: Do not use the injection if it contains precipitate.

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Pregnancy: Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with Sodium Bicarbonate. It is also not known whether Sodium Bicarbonate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Bicarbonate should be given to a pregnant woman only if clearly needed.

Pediatric

Rapid injection (10 mL/min) of hypertonic Sodium Bicarbonate Injection, USP solutions into neonates and children under two years of age may produce hypernatremia, a decrease in cerebrospinal fluid pressure and possible intracranial hemorrhage. The rate of administration in such patients should therefore be limited to no more than 8 mEq/kg/day. A 4.2% solution may be preferred for such slow administration. In emergencies such as cardiac arrest, the risk of rapid infusion must be weighed against the potential for fatality due to acidosis.

Geriatric

Clinical studies of Sodium Bicarbonate Injection, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Sodium Bicarbonate Injection Adverse Reactions

Overly aggressive therapy with Sodium Bicarbonate Injection, USP can result in metabolic alkalosis (associated with muscular twitchings, irritability, and tetany) and hypernatremia.

Inadvertent extravasation of intravenously administered hypertonic solutions of Sodium Bicarbonate have been reported to cause chemical cellulitis because of their alkalinity, with tissue necrosis, ulceration or sloughing at the site of infiltration. Prompt elevation of the part, warmth and local injection of lidocaine or hyaluronidase are recommended to reduce the likelihood of tissue sloughing from extravasated I.V. solutions.

Sodium Bicarbonate Injection Overdosage

Should alkalosis result, the bicarbonate should be stopped and the patient managed according to the degree of alkalosis present. 0.9% sodium chloride injection intravenous may be given; potassium chloride also may be indicated if there is hypokalemia. Severe alkalosis may be accompanied by hyperirritability or tetany and these symptoms may be controlled by calcium gluconate. An acidifying agent such as ammonium chloride may also be indicated in severe alkalosis.

Sodium Bicarbonate Injection Dosage and Administration

Sodium Bicarbonate Injection, USP is administered by the intravenous route.

In cardiac arrest, a rapid intravenous dose of one to two 50 mL syringes (44.6 to 100 mEq) may be given initially and continued at a rate of 50 mL (44.6 to 50 mEq) every 5 to 10 minutes if necessary (as indicated by arterial pH and blood gas monitoring) to reverse the acidosis. Caution should be observed in emergencies where very rapid infusion of large quantities of bicarbonate is indicated. Bicarbonate solutions are hypertonic and may produce an undesirable rise in plasma sodium concentration in the process of correcting the metabolic acidosis. In cardiac arrest, however, the risks from acidosis exceed those of hypernatremia.

In less urgent forms of metabolic acidosis, Sodium Bicarbonate Injection, USP may be added to other intravenous fluids. The amount of bicarbonate to be given to older children and adults over a four-to-eight-hour period is approximately 2 to 5 mEq/kg of body weight – depending upon the severity of the acidosis as judged by the lowering of total CO2 content, blood pH and clinical condition of the patient. In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. Bicarbonate therapy should always be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable. Initially an infusion of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours will produce a measurable improvement in the abnormal acid-base status of the blood. The next step of therapy is dependent upon the clinical response of the patient. If severe symptoms have abated, then the frequency of administration and the size of the dose may be reduced.

In general, it is unwise to attempt full correction of a low total CO2 content during the first 24 hours of therapy, since this may be accompanied by an unrecognized alkalosis because of a delay in the readjustment of ventilation to normal. Owing to this lag, the achievement of total CO2 content of about 20 mEq/liter at the end of the first day of therapy will usually be associated with a normal blood pH. Further modification of the acidosis to completely normal values usually occurs in the presence of normal kidney function when and if the cause of the acidosis can be controlled. Values for total CO2 which are brought to normal or above normal within the first day of therapy are very likely to be associated with grossly alkaline values for blood pH, with ensuing undesired side effects.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Before using sodium bicarbonate medication

In deciding to use sodium bicarbonate medication, the risks of taking sodium bicarbonate medication must be weighed against the good it will do. This is a decision you and your doctor will make. For sodium bicarbonate medication, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children

Antacids should not be given to young children (up to 6 years of age) unless prescribed by a physician. This medicine may not help and may even worsen some conditions, so make sure that your child’s problem should be treated with this medicine before you use it.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of sodium bicarbonate in the elderly with use in other age groups.

Pregnancy

Pregnancy Category C (all Trimesters): Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

It is not known whether sodium bicarbonate will harm an unborn baby. However, sodium bicarbonate can cause fluid to build up in your body, which may be dangerous during pregnancy. DO NOT use sodium bicarbonate without a doctor’s advice if you are pregnant.

Breastfeeding

It is not known whether sodium bicarbonate passes into breast milk or if it could harm a nursing baby. Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding. However, do not use sodium bicarbonate without a doctor’s advice if you are breast-feeding a baby.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using sodium bicarbonate medication with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acalabrutinib
• Amphetamine
• Benzphetamine
• Dextroamphetamine
• Digoxin
• Elvitegravir
• Gefitinib
• Ketoconazole
• Ledipasvir
• Lisdexamfetamine
• Mefenamic Acid
• Memantine
• Methamphetamine
• Pazopanib
• Rilpivirine

Sodium bicarbonate interactions ¹

• Concurrent use of citrates with sodium bicarbonate may promote the development of calcium stones in patients with uric acid stones, due to sodium ion opposition to the hypocalciuric effect of the alkaline load; may also cause hypernatremia.
• Alkalinization of the urine may reduce the solubility of ciprofloxacin, norfloxacin, or ofloxacin in the urine; patients should be observed for signs of crystalluria and nephrotoxicity.
• Antacids may alkalinize the urine and counteract the effect of urinary acidifiers such as ammonium chloride, ascorbic acid and potassium or sodium phosphates; frequent use of antacids, especially in high doses, is best avoided by patients receiving therapy to acidify the urine.
• Alkalinization of the urine caused by sodium bicarbonate may reduce the effectiveness of methenamine by inhibiting its conversion to formaldehyde; concurrent use is not recommended.
• Concurrent and prolonged use /of calcium-containing preparations or milk or milk products with sodium bicarbonate may result in the milk-alkali syndrome.
• Concurrent use of anticholinergics or other medications with anticholinergic action with sodium bicarbonate may decrease absorption, reducing the effectiveness of the anticholinergic; doses of these medications should be spaced 1 hour apart from doses of sodium bicarbonate; also, urinary excretion may be delayed by alkalinization of the urine, thus potentiating the side effects of the anticholinergic.
• Urinary excretion may be inhibited when these medications amphetamines or quinidine are used concurrently with sodium bicarbonate, possibly resulting in toxicity; dosage adjustment may be needed when sodium bicarbonate therapy is initiated or discontinued or if dosage is changed.
• Absorption may be decreased when oral tetracyclines are used concurrently with sodium bicarbonate because of increase in intragastric pH; patients should be advised not to take sodium bicarbonate within 1 to 2 hours of tetracyclines.
• Concurrent use of sucralfate with sodium bicarbonate may be indicated in the treatment of duodenal ulcer to relieve pain; however, simultaneous administration is not recommended since antacids, such as sodium bicarbonate, may interfere with binding of sucralfate to the mucosa; patients should be advised not to take sodium bicarbonate within one-half hour before or 1 hour after sucralfate.
• Marked alkalinization of the urine caused by sodium bicarbonate may retard renal excretion of mexiletine.
• Alkalinization of the urine caused by sodium bicarbonate slows excretion and prolongs the effects of mecamylamine; concurrent use is not recommended.
• Sodium bicarbonate enhances lithium excretion, possibly resulting in decreased efficacy; this may be partly due to the sodium content.
• Sodium bicarbonate may cause increased gastrointestinal pH; concurrent administration of ketoconazole with sodium bicarbonate may result in a marked reduction in absorption of ketoconazole; patients should take sodium bicarbonate at least 2 hours after ketoconazole.
• Absorption may be decreased when oral iron supplements or preparations are used concurrently with antacids containing carbonate; because of the formation of less soluble complexes, iron supplements should not be taken within 1 hour before or 2 hours after sodium bicarbonate.
• Concurrent use of cimetidine, famotidine, nizatidine, or ranitidine with sodium bicarbonate may be indicated in the treatment of peptic ulcer to relieve pain; however, simultaneous administration of antacids of medium to high potency (80 mmol to 150 mmol HCl) is not recommended since absorption of these medications may be decreased; patients should be advised not to take any antacids within one-half to 1 hour of histamine H 2-receptor antagonists.
• Urine alkalinization induced by sodium bicarbonate may increase the half life of ephedrine and prolong its duration of action, especially if the urine remains alkaline for several days or longer; dosage adjustment of ephedrine may be necessary.
• Itraconazole concentration decreased by simultaneous antacids administration which decrease gastric acidity ².
• Renal tubular acidosis induced by maleic acid causes diuresis that results in increased excretion of sodium bicarbonate, glucose, phosphate, amino acids, and chloride. Based on the effects of maleic acid on mitochondrial energy metabolism and cellular ATP levels, the principal transport abnormality identified by microperfusion of rat proximal tubule bicarbonate transport was impaired basolateral membrane-active sodium transport ³.
• Serum sodium bicarbonate levels are often depressed /in ethylene glycol poisoning ⁴.

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Appendicitis or
• Intestinal or rectal bleeding—Oral forms of sodium bicarbonate may make these conditions worse:
• Edema (swelling of feet or lower legs) or
• Heart disease or
• High blood pressure (hypertension) or
• Kidney disease or
• Liver disease or
• Problems with urination or
• Toxemia of pregnancy—Sodium bicarbonate may cause the body to retain (keep) water, which may make these conditions worse

Who may not be able to take sodium bicarbonate

Antacids are safe for most people to take, although they aren’t suitable for everyone.

Speak to a pharmacist or your doctor for advice first if you:

• are pregnant or breastfeeding – most sodium bicarbonate are considered safe to take while pregnant or breastfeeding, but always get advice first
• are looking for a medicine for a child under 12 years of age – some antacids are not recommended for children
• have liver disease, kidney disease or heart failure – sodium bicarbonate may not be safe if you have one of these problems
• have an illness that means you need to control how much salt (sodium) is in your diet, such as high blood pressure or cirrhosis (liver scarring) – sodium bicarbonate contains high levels of sodium, which could make you unwell
• are taking other medicines – sodium bicarbonate can interfere with other medications and may need be avoided or taken at a different time.

What is sodium bicarbonate used for

Sodium bicarbonate (NaHCO₃) may help if you have:

• indigestion
• heartburn or acid reflux – also known as gastro-esophageal reflux disease (GERD)
• a stomach ulcer
• gastritis (inflammation of the stomach lining)

They can quickly relieve your symptoms for a few hours. But they don’t treat the underlying cause and long-term use isn’t recommended.

Speak to your doctor if you find you need to take antacids regularly.

Sodium bicarbonate uses

For safe and effective use of sodium bicarbonate:

• Follow your doctor’s instructions if this medicine was prescribed.
• Follow the manufacturer’s package directions if you are treating yourself.

For patients taking this medicine for a stomach ulcer:

• Take it exactly as directed and for the full time of treatment as ordered by your doctor, to obtain maximum relief of your symptoms.
• Take it 1 and 3 hours after meals and at bedtime for best results, unless otherwise directed by your doctor.

Sodium bicarbonate dosage

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For sodium bicarbonate effervescent powder

To relieve heartburn or sour stomach:

• Adults and teenagers—3.9 to 10 grams (1 to 2½ teaspoonfuls) in a glass of cold water after meals. However, the dose is usually not more than 19.5 grams (5 teaspoonfuls) a day.
• Children up to 6 years of age—Dose must be determined by your doctor.
• Children 6 to 12 years of age—1 to 1.9 grams (¼ to ½ teaspoonful) in a glass of cold water after meals.

For sodium bicarbonate powder

To relieve heartburn or sour stomach:

• Adults and teenagers—One-half teaspoonful in a glass of water every two hours. Your doctor may change the dose if needed.
• Children—Dose must be determined by your doctor.

To make the urine more alkaline (less acidic):

• Adults and teenagers—One teaspoonful in a glass of water every four hours. Your doctor may change the dose if needed. However, the dose is usually not more than 4 teaspoonfuls a day.
• Children—Dose must be determined by your doctor.

For sodium bicarbonate tablets

To relieve heartburn or sour stomach:

• Adults and teenagers—325 milligrams (mg) to 2 grams one to four times a day.
• Children up to 6 years of age—Dose must be determined by your doctor.
• Children 6 to 12 years of age—The dose is 520 mg. The dose may be repeated in thirty minutes.

To make the urine more alkaline (less acidic):

• Adults and teenagers—At first, four grams, then 1 to 2 grams every four hours. However, the dose is usually not more than 16 grams a day.
• Children—The dose is based on body weight and must be determined by your doctor. The usual dose is 23 to 230 mg per kilogram (kg) (10.5 to 105 mg per pound) of body weight a day. Your doctor may change the dose if needed.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Usual Adult Dose for Metabolic Acidosis

Parenteral:
If acid-base status is available, dosages should be calculated as follows: 0.2 x weight (kg) x base deficit.

Alternatively:

HCO3 (mEq) required = 0.5 x weight (kg) x [24 – serum HCO3 (mEq/L)].

or

Moderate metabolic acidosis: 50 to 150 mEq sodium bicarbonate diluted in 1 L of D5W to be intravenously infused at a rate of 1 to 1.5 L/hour during the first hour.

Severe metabolic acidosis: 90 to 180 mEq sodium bicarbonate diluted in 1 L of D5W to be intravenously infused at a rate of 1 to 1.5 L/hour during the first hour.

If acid-base status is not available, dosages should be calculated as follows: 2 to 5 mEq/kg IV infusion over 4 to 8 hours; subsequent doses should be based on patient’s acid-base status.

Oral:

Moderate metabolic acidosis: 325 to 2000 mg orally 1 to 4 times a day. One gram provides 11.9 mEq (mmoL) each of sodium and bicarbonate.

Usual Adult Dose for Diabetic Ketoacidosis

Although sodium bicarbonate is approved for the treatment of metabolic acidosis, data have shown that the use of this drug may be harmful in certain clinical settings such as lactic acidosis, acidosis with tissue hypoxia, uremia, severe cardiac dysfunction or arrest, and diabetic ketoacidosis.

Most experts only allow for its use when tissue perfusion and ventilation are maximized and the arterial pH is 7.1 or lower.

If sodium bicarbonate is used to treat diabetic ketoacidosis, the initial dosage is 50 mEq sodium bicarbonate in 1 L of appropriate IV solution to be given once.

Insulin therapy may obviate the need for bicarbonate therapy since it will promote glucose utilization and decrease the production of ketoacids.

Usual Adult Dose for Urinary Alkalinization

Parenteral:

50 to 150 mEq sodium bicarbonate diluted in 1 L of D5W to be intravenously infused at a rate of 1 to 1.5 L/hour.

Oral:

325 to 2000 mg orally 1 to 4 times a day. One gram provides 11.9 mEq (mmoL) each of sodium and bicarbonate.

The goal of therapy is to correct serum pH and increase the urinary pH to 8 in order to increase the renal excretion of toxic substances such as salicylates or lithium.

If the increase in urinary pH is inadequate, increasing the sodium bicarbonate in solution to 100 to 150 mEq/L may result in further alkalinization of the urine.

Usual Adult Dose for Dyspepsia

325 to 2000 mg orally 1 to 4 times a day.

Usual Adult Dose for Hyperkalemia

One ampule of 7.5% sodium bicarbonate (44.6 mEq HCO3 ion) may be administered slowly IV over 5 minutes and repeated at 10 to 15 minute intervals if ECG changes persist. The onset of action occurs within 30 minutes and the effect lasts for 1 to 2 hours. The resultant effect restores intracellular potassium levels to normal without decreasing total body potassium stores.

Circulatory overload and hypernatremia can occur when large volumes of hypertonic sodium bicarbonate are given. If hypocalcemia is present, seizures and tetany may occur as blood pH rises and the ionized free calcium decreases; hence, calcium should be given first. Hyponatremia will magnify the cardiac effects of hyperkalemia, and sodium bicarbonate can be used to treat this as well.

Usual Adult Dose for Asystole

1 mEq/kg slow IV initially, may repeat with 0.5 mEq/kg 10 minutes later one time, or as indicated by the patient’s acid-base status.

Usual Pediatric Dose for Metabolic Acidosis

If acid-base status is available, dosages should be calculated as follows:
Infants and Children: HCO3 (mEq) required = 0.3 x weight (kg) x base deficit (mEq/L) OR HCO3 (mEq) required = 0.5 x weight (kg) x [24 – serum HCO3 (mEq/L)].

If acid-base status is not available, dosages should be calculated as follows:

Older children: 2 to 5 mEq/kg IV infusion over 4 to 8 hours; subsequent doses should be based on patient acid-base status.

Usual Pediatric Dose for Urinary Alkalinization

0 to 12 years: 1 to 10 mEq (84 to 840 mg)/kg/day orally in divided doses; dose should be titrated to desired urinary pH.

Greater than 12 to 18 years: 325 to 2000 mg orally 1 to 4 times a day. One gram provides 11.9 mEq (mmol) each of sodium and bicarbonate.

The goal of therapy is to correct serum pH and increase the urinary pH to 8 in order to increase the renal excretion of toxic substances such as salicylates or lithium.

If the increase in urinary pH is inadequate, increasing the sodium bicarbonate in solution to 100 to 150 mEq/L may result in further alkalinization of the urine.

Usual Pediatric Dose for Hyperuricemia Secondary to Chemotherapy

0 to 12 years:

Parenteral:
120 to 200 mEq/m2/day diluted in maintenance IV fluids of 3000 mL/m2/day; titrate to maintain urine pH between 6 and 7.

Oral:
12 g/m2/day divided into 4 doses; titrate to maintain urine pH between 6 and 7.

Usual Pediatric Dose for Asystole

1 mEq/kg slow IV initially, may repeat with 0.5 mEq/kg 10 minutes later one time, or as indicated by the patient acid-base status.

Renal Dose Adjustments

Due to the risk of hypernatremia, electrolyte shifts, and systemic pH changes, it is recommended that sodium bicarbonate be used with caution due to this patient’s renal dysfunction. Close monitoring of this patient’s plasma electrolytes and bicarbonate is recommended, particularly if dose increments are considered.

Liver Dose Adjustments

Due to the risk of hypernatremia, electrolyte shifts, and systemic pH changes, it is recommended that sodium bicarbonate be used with caution due to the patient’s liver disease. Close monitoring of this patient’s plasma electrolytes and bicarbonate is recommended, particularly if dose increments are considered.

Dialysis

Sodium bicarbonate is removed by peritoneal dialysis. Bicarbonate has been commonly used in the peritoneal dialysate to raise the pH in patients in whom the standard pH of 5.5 causes abdominal discomfort on inflow.

Sodium bicarbonate is removed by hemodialysis. Bicarbonate has been commonly used in the dialysate bath to correct metabolic acidosis, and has been used preferentially over acetate for patients with marked hemodynamic instability due to sepsis or other causes, particularly patients requiring vasopressor support. Bicarbonate dialysate is also used for high-flux and high-efficiency dialysis with K/V greater than 5.5 mL/min/L.

Other Comments

A gradual rise in the plasma bicarbonate concentration up to the normal range over a 12 to 24 hour period is recommended as opposed to a rapid “correction” of the patient’s entire bicarbonate deficit. Rapid correction of the deficit can cause hypokalemic cardiotoxicity in patients who are potassium-depleted, tetany in patients with renal failure or hypocalcemia or congestive heart failure in patients with poor left ventricular function due to the excess sodium load from this medication). Other possible side effects include systemic alkalosis and/or CNS acidosis. Further bicarbonate therapy depends on the patient’s plasma bicarbonate level.

In patients with lactic acidosis, resolution of the event responsible for the acidosis is the primary treatment. While severe lactic acidosis can contribute to circulatory collapse, treatment with sodium bicarbonate may promote lactate production. In general, sodium bicarbonate may be beneficial if the plasma bicarbonate is less than 8 mEq/L or the systemic pH is less than 7.1.

How and when to take sodium bicarbonate

Check the instructions on the packet or leaflet to see how much sodium bicarbonate to take and how often. This depends on the reasons for taking sodium bicarbonate.

Sodium bicarbonate should be used when you have symptoms or think you will get them soon – for most people, the best time to take sodium bicarbonate is with or soon after meals, and just before going to bed.

Remember that doses for children may be lower than for adults.

How should I take sodium bicarbonate?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Sodium bicarbonate tablets are usually dissolved completely in water before swallowing. Follow al directions on the product label.

Call your doctor if your symptoms do not improve, or if they get worse while using sodium bicarbonate.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since sodium bicarbonate is used when needed, you may not be on a dosing schedule. Do not take more of this medicine than recommended on the product label.

What should I avoid while taking sodium bicarbonate?

Avoid taking this medicine without a doctor’s advice if you regularly take other medicines.

Sodium bicarbonate side effects

Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism ⁵.

Sodium bicarbonate don’t usually have many side effects if they’re only taken occasionally and at the recommended dose.

Common side effects may include:

• dry mouth;
• increased thirst; or
• urinating more than usual.

But sometimes sodium bicarbonate can cause:

• diarrhea or constipation
• flatulence (wind)
• stomach cramps
• feeling sick or vomiting

These should pass once you stop taking sodium bicarbonate medicine.

Check with your doctor as soon as possible if any of the following side effects occur while taking sodium bicarbonate:

• frequent urge to urinate
• headache (continuing)
• loss of appetite (continuing)
• mood or mental changes
• muscle pain or twitching
• nausea or vomiting
• nervousness or restlessness
• slow breathing
• swelling of feet or lower legs
• unpleasant taste
• unusual tiredness or weakness

Some side effects of sodium bicarbonate may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less Common

• Increased thirst
• stomach cramps

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

Speak to a pharmacist or your doctor if they don’t improve or are troublesome. You may need to switch to another medicine.

• Volume expansion can increase blood pressure and promote edema, so that use of even moderate amt of sodium bicarbonate may be hazardous to persons with renal insufficiency or incipient or active hypertension or cardiac failure ⁶.
• Sodium bicarbonate should be used with extreme caution in patients with congestive heart failure or other edematous or sodium-retaining conditions; in patients with renal insufficiency, especially those with severe insufficiency such as oliguria or anuria ⁷.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using sodium bicarbonate and call your doctor at once if you have:

• severe stomach pain;
• swelling, rapid weight gain; or
• shortness of breath (even with mild exertion).

Metabolic

Chronic ingestion of bicarbonate may rarely cause intravascular volume expansion with resultant hyporeninemia and hypoaldosteronemia. In this rare circumstance, the serum potassium may be elevated.

Rare cases of sodium bicarbonate abuse have been associated with features of Munchausen syndrome. These patients often present with an otherwise unexplained hypokalemic hypochloremic metabolic alkalosis.

Hypernatremia may cause water retention, weight gain, and edema, which may be important in some patients with congestive heart failure, renal insufficiency, or severe liver disease.

Metabolic side effects have included metabolic alkalosis, hypernatremia/hyperosmolarity, hypochloremia, and hypokalemia. These effects have been associated with rapid or prolonged administration. Side effects have rarely included intravascular volume expansion with resultant hyporeninemia and hypoaldosteronemia.

Respiratory

The respiratory drive may be suppressed after bicarbonate administration due to increased venous C02 concentration. Without adequate ventilation, worsened systemic acidosis could develop.

Respiratory side effects have included suppressed respiratory drive.

Nervous system

Rapid infusion of hyperosmolar sodium bicarbonate has been associated with intraventricular hemorrhage in the pediatric literature.

Irritability and tetany have been associated with sodium bicarbonate-induced alkalosis or hypernatremia.

Due to greater permeability of the blood-brain barrier to hydrogen than to bicarbonate, the pH of cerebrospinal fluid may significantly decrease during sodium bicarbonate administration, which can cause mental stupor or coma.

Nervous system side effects have included irritability, tetany, mental stupor, coma, and intraventricular hemorrhage.

Local side effects

Local side effects have included IV site pain, venous irritation, and extravasation. Cellulitis, tissue necrosis, ulceration, or skin sloughing have possibly been the result of extravasation. A slow rate of administration of a properly diluted solution into a large bore needle and vein is recommended if IV administration is necessary.

Cardiovascular

Cardiovascular side effects have included decreased cardiac contractility possibly resulting from infusion of sodium bicarbonate in patients with severe acidosis.

Experimentally, the administration of intravenous hypertonic sodium bicarbonate has been associated with increased serum osmolality, decreased ionized serum calcium (which is associated with decreased myocardial contractility), and peripheral vasodilation. Some experts recommend invasive hemodynamic monitoring in acidotic patients before the administration of bicarbonate.

Gastrointestinal

Gastrointestinal side effects associated with oral administration have rarely included gastric rupture.

As an antacid, sodium bicarbonate, especially after excess food or liquid, can cause excess gas release (when combined with gastric acid). The mortality associated with gastric rupture is as high as 65%.

Renal

Urinary alkalinization from bicarbonate can cause a falsely positive colorimetric assay for protein.

Renal side effects have rarely included “False proteinuria”.

Human Toxicity Reports

With a combination of 380 milliequivalent (mEq) of sodium bicarbonate and 640 mEq of calcium carbonate/day only 10% of 1350 patients developed alkalosis ⁸. Daily doses up to 25 milliequivalent (mEq)/kg /were administered/ to patients for 3 weeks. Changes in plasma electrolyte concentration were not remarkable; plasma total carbon dioxide increased by only 5 mEq/L with largest dose. Considerable weight gain was most prominent effect ⁸.

In neutralizing gastric acid, distention and possible damage or rupture of the stomach may occur from carbon dioxide release ⁹.

When large doses of sodium bicarbonate (NaHCO₃) and/or calcium bicarbonate (CaHCO₃) were administered with milk or cream for the management of peptic ulcer, the milk-alkali syndrome occurred frequently. This syndrome results from large quantities of Ca²+ and absorbable alkali; effects consist of hypercalcemia, reduced secretion of parathyroid hormone, retention of phosphate, precipitation of Ca²+ salts in the kidney, and renal insufficiency. Therapeutic regimens emphasizing the use of dairy products seldom are employed in current practice ¹⁰.

Large doses of sodium bicarbonate (NaHCO₃), particularly in patients with renal insufficiency, have produced systemic alkalosis and/or an expansion in the extracellular fluid volume with edema. Frank hypocalcemic tetany accompanied by hypoglycemia has occurred in 9-yr old girl ⁹.

A case of baking soda pica in a woman at 31 weeks of pregnancy causing severe hypokalemic metabolic alkalosis and rhabdomyolysis was reported ¹¹. A multigravida at 31 weeks of gestation presented with weakness and muscle pain. She was found to have severe hypokalemic metabolic alkalosis and rhabdomyolysis, with elevation in serum transaminases and hypertension. It was initially thought the patient had an atypical presentation of preeclampsia until it was realized that she was ingesting 1 full box of baking soda (454 g sodium bicarbonate) per day ¹¹. Symptoms and abnormal laboratory findings resolved with discontinuation of the patient’s pica practices. Pica is a common but often overlooked practice that can potentially lead to life-threatening disorders. A thorough evaluation of a patient’s dietary intake is extremely important, especially in the setting of atypical presentations of disease in pregnancy.

The anticoagulant effects of sodium bicarbonate was investigated in fresh human whole blood obtained from normal healthy volunteers. Prothrombin and thrombin clotting time determination indicated that bicarbonate can interfere with the clotting process ¹².

Sodium bicarbonate hazards

Reactivity Alerts

none

Air & Water Reactions

Stable in dry air, but slowly decomposes in moist air. Moderately water soluble. Decomposes slowly in water (accelerated by agitation) ¹³.

Fire Hazard

Literature sources indicate that this chemical is noncombustible ¹³.

Health Hazard

Symptoms of exposure to this compound include irritation of the skin, eyes, nose and throat, coughing, chest discomfort and gastrointestinal disturbance. It may cause distention or rupture of the stomach, systemic alkalosis, edema and expansion of extracellular fluid volume. Severe alkalosis may be characterized by hyperirritability and tetany. It can cause cerebral edema leading to death. It may also cause renal injury.

When heated to decomposition this compound emits toxic fumes of carbon monoxide, carbon dioxide and sodium oxides ¹³.

Reactivity Profile

Sodium bicarbonate (NaHCO₃) reacts exothermically with acids to generate non-toxic carbon dioxide gas. Decomposes when heated. Incompatible with acids, acidic salts (dopamine hydrochloride, pentazocine lactate, many alkaloidal salts) aspirin and bismuth salicylate.

First Aid

EYES: First check the victim for contact lenses and remove if present. Flush victim’s eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim’s eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim’s airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital.

References

1. Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2006.
2. Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1303
3. Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty’s Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 5:842
4. Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty’s Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 7:8
5. Thomas SH, Stone CK; Am J Emerg Med 12 (1): 57-9; 1994
6. Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 966
7. McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 2590
8. Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 994
9. Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-125
10. Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 1013
11. Grotegut CA et al; Obstet Gynecol 107 (2 Pt 2) 484-6;2006
12. Wong DW et al; J Am Med Assoc 244 (1): 61; 1980
13. The National Toxicology Program. https://ntp.niehs.nih.gov/

What is ranitidine

Ranitidine is a class of medications called histamine-2 blockers (H2 blockers) and ranitidine works by reducing the amount of acid your stomach produces. Ranitidine is used to treat and prevent ulcers in the stomach and intestines. Ranitidine also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Ranitidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn and injury of the food pipe (esophagus).

Over-the-counter ranitidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach.

Ranitidine comes as tablets, soluble (dispersible) tablets that dissolve in water to make a drink, or as a liquid that you drink.

All types of ranitidine are available on prescription. You can also buy the lowest strength 75mg tablets from pharmacies and supermarkets.

Key facts

• It’s usual to take ranitidine once or twice a day.
• Some people only need to take ranitidine for a short time, when they have symptoms. Others need to take it for longer.
• You can take ranitidine with or without food.
• It’s unusual to get any side effects. However, some people may get stomach pain or constipation, or feel sick (nausea). This tends to get better as you carry on taking ranitidine.
• Ranitidine is called by the brand names Zantac, Zantac 75, Zantac EFFERdose, Zantac Syrup and Taladine

Ranitidine mechanism of action

Ranitidine is a histamine-2 antagonist or H2 blocker. Ranitidine works by reducing the amount of acid your stomach produces. Histamine is a chemical that occurs naturally in your body. Histamine encourages your stomach to produce acid which it needs to digest your food. By blocking the histamine, ranitidine reduces the amount of acid your stomach produces. Having less acid in your stomach allows ulcers and inflammation to heal. If your foodpipe (esophagus) has been damaged by stomach acid, this will also have a chance to heal.

Before taking ranitidine – Precautions

• tell your doctor and pharmacist if you are allergic to ranitidine or any other medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention either of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); and triazolam (Halcion). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had porphyria, phenylketonuria, or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ranitidine, call your doctor.
• Using ranitidine may increase your risk of developing pneumonia. Symptoms of pneumonia include chest pain, fever, feeling short of breath, and coughing up green or yellow mucus. Talk with your doctor about your specific risk of developing pneumonia.

How much ranitidine is safe to take?

Ranitidine comes as a tablet, an effervescent tablet, effervescent granules, and a syrup to take by mouth. Each tablet contains 75mg, 150mg or 300mg of ranitidine. You can buy 75mg tablets in pharmacies and supermarkets. Soluble tablets, and 150mg and 300mg tablets are only available on prescription.

Ranitidine is usually taken once a day at bedtime or two to four times a day. Over-the-counter ranitidine comes as a tablet to take by mouth. It is usually taken once or twice a day. To prevent symptoms, it is taken 30 to 60 minutes before eating or drinking foods that cause heartburn. Follow the directions on your prescription or the package label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ranitidine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Dissolve ranitidine effervescent tablets and granules in a full glass (6 to 8 ounces [180 to 240 milliliters]) of water before drinking.

Do not take over-the-counter ranitidine for longer than 2 weeks unless your doctor tells you to. If symptoms of heartburn, acid indigestion, or sour stomach last longer than 2 weeks, stop taking ranitidine and call your doctor.

The usual dose to treat:

• indigestion or heartburn is 75mg to 300mg ranitidine a day
• stomach ulcers and inflammation of the food pipe is 300mg to 600mg ranitidine a day
• Zollinger-Ellison syndrome is 450mg to 6 grams ranitidine a day

Ranitidine liquid comes in 2 different strengths – your daily dose will depend on what your doctor prescribes. Follow your doctor’s advice about how much ranitidine to take and when.

• Doses are usually lower for children and people with kidney problems.

If a doctor prescribes ranitidine for your child, they will use your child’s weight or age to work out the right dose.

How long does ranitidine take to work

Your indigestion and heartburn should start to feel better within 1 or 2 hours. The effects will usually last for around 12 hours.

It may take a few weeks for ranitidine to work properly. Depending on your problems, you may still have some acid symptoms during this time.

If you’re taking ranitidine to prevent stomach ulcers, however, you may not feel any different. Carry on taking your medicine. It will still be working.

How long will I take ranitidine for?

If you’re taking lower strength ranitidine (75mg) that you bought from a pharmacy or supermarket, speak to a pharmacist or doctor before starting on a second packet. They may recommend tests to find out what’s causing your symptoms, if taking ranitidine hasn’t cleared them up.

If your doctor prescribes ranitidine for you, you may only need to take it for a few weeks or months, depending on your health problem. Sometimes you might need to take it for longer.

Your doctor may suggest taking ranitidine only when you have symptoms. This means you won’t have to take it every day. Once you feel better, you can stop taking it – often after a few days or weeks.

Taking ranitidine this way isn’t suitable for everyone. Speak to your doctor about what’s best for you.

Although ranitidine appears to only minimally affect the secretion of gastric intrinsic factor, malabsorption of, and resultant deficiency in vitamin B12 may occur during long-term ranitidine therapy ¹.

Is it safe to take ranitidine every day?

It’s usually best to take ranitidine for a short time. You might take it for a month or two, for example, until your stomach heals. Some people may take it every now and again when they have symptoms. You may find that ranitidine stops working and your symptoms come back if you take it for longer than this.

If you’re taking ranitidine to treat Zollinger Ellison syndrome or another long term problem, however, you may need to take it for longer. In this case, follow your doctor’s instructions about the best way to take it.

Are there similar medicines to ranitidine?

There are 3 other medicines that are similar to ranitidine. They are cimetidine, famotidine and nizatidine.

Like ranitidine, these medicines are H2 blockers. They work in the same way as ranitidine to reduce the amount of acid in your stomach.

Famotidine and nizatidine generally work as well as ranitidine and have similar side effects. However they may suit some people better.

Cimetidine can interfere with lots of medicines and has more side effects than other H2 blockers.

Are there other indigestion medicines?

Yes there are other pharmacy and prescription medicines for indigestion and heartburn.

Antacids, like calcium carbonate (Tums or Mylanta), sodium bicarbonate (Neut), Maalox and Milk of Magnesia, relieve indigestion and heartburn by neutralizing the acid in your stomach. They give quick relief that lasts for a few hours. They’re ideal for occasional stomach acid symptoms.

Some antacids, such as Gaviscon, have an extra ingredient called alginic acid. They work by lining your stomach so that juices from it don’t splash up into your foodpipe. They’re especially good for relieving acid reflux.

Antacids are available from pharmacies and supermarkets.

Proton pump inhibitors (PPIs) reduce the amount of acid made in your stomach, but they do this in a different way to H2 blockers.

They include esomeprazole (Nexium), lansoprazole (Zoton FasTabs), omeprazole (Losec), pantoprazole (Pantoloc Control) and rabeprazole (Pariet).

In general, proton pump inhibitors (PPIs) are used first because they are better than H2 blockers at reducing stomach acid. Your doctor may prescribe an H2 blocker if you don’t get on with a proton pump inhibitor (PPI) – for example because of the side effects.

Lansoprazole and rabeprazole are only available on prescription but you can buy omeprazole, esomeprazole and pantoprazole directly from pharmacies. You can also buy esomeprazole from supermarkets.

Can I take ranitidine with other indigestion medicines?

Some antacids are okay to take at the same time as ranitidine. Other antacids, such as Gaviscon, need to be taken a certain amount of time before or after you take the ranitidine. Check the instructions on the packet to see how long you need to wait between medicines.

Sometimes, depending on your symptoms, your doctor may prescribe an H2 blocker as well as a proton pump inhibitor. This will often be for a short time and you’ll usually take the H2 blocker at night.

If you’re prescribed sucralfate (a medicine to treat ulcers), take it at least 2 hours after ranitidine. This is because sucralfate can stop your body from properly absorbing the ranitidine.

Can I drive or ride a bike after taking ranitidine?

Occasionally, ranitidine can make you feel dizzy or sleepy, or give you blurred vision. If this happens to you, don’t drive, cycle or use machinery or tools until you feel better.

Furthermore, the amount of alcohol contained in a large dose of ranitidine liquid may affect your ability to drive or operate machines. In this case, do not attempt to drive or use any machinery.

Can I drink alcohol with ranitidine?

Yes, you can drink alcohol with ranitidine but be aware that ranitidine liquid also contains a small amount of alcohol.

Also, drinking alcohol makes your stomach produce more acid than normal. This can irritate your stomach lining and make your symptoms worse.

Is there any food or drink I need to avoid?

You can eat and drink normally while taking ranitidine.

However, it’s best to avoid foods that seem to make your indigestion worse, such as rich, spicy and fatty foods. You may also want to cut down on caffeinated drinks, such as tea, coffee and cola, as well as alcohol.

Can lifestyle changes help?

It may be possible to ease symptoms caused by too much stomach acid by making a few changes to your diet and lifestyle:

• lose excess weight
• don’t eat foods that can make your symptoms worse, such as rich, spicy and fatty foods, and acidic foods like tomatoes, citrus fruits, salad dressings and fizzy drinks
• cut down on caffeinated drinks, such as tea, coffee and cola, as well as alcohol and smoking
• if you have symptoms at night, try not to eat for at least 3 hours before you go to bed
• raise the head of your bed by 10 to 20cm, so your head and chest are higher than your waist

Who can and can’t take ranitidine

Ranitidine can be taken by adults. It can also be given to children under 16 years of age on prescription.

Ranitidine isn’t suitable for some people. To make sure that it is safe for you, tell your doctor if you:

• have had an allergic reaction to ranitidine or any other medicines in the past
• have kidney problems
• have an intolerance to, or cannot absorb, some sugars such as fructose
• have been advised to eat a low calcium or low salt diet
• cannot have alcohol – ranitidine liquid contains a small amount of alcohol
• have phenylketonuria (PKU), a rare inherited illness

If you’re due to have an endoscopy to find out what’s causing your symptoms, stop taking ranitidine at least 2 weeks before your procedure. This is because ranitidine may hide some of the problems that would usually be spotted during an endoscopy.

Pediatric Use

The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Use of ranitidine in this age-group is supported by adequate and well-controlled trials in adults, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature.

Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established.

Safety and effectiveness in neonates (aged younger than 1 month) have not been established.

Geriatric Use

Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of ranitidine, for which there were subgroup analyses, 4,197 were aged 65 and older, while 899 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function.

Pregnancy and breastfeeding

Tell your pharmacist or doctor if you’re trying to get pregnant, are already pregnant or if you’re breastfeeding.

Usually, ranitidine is safe to take during pregnancy and while breastfeeding. Animal models have failed to reveal evidence of impaired fertility or fetal harm. It is unknown whether use of gastric-suppressing drugs are associated with childhood allergy and asthma. There are no controlled data in human pregnancy.

If you’re pregnant, it’s always better to try to treat indigestion without taking a medicine.

Your doctor or midwife will first advise you to try to ease your symptoms by eating smaller meals more often, and not eating fatty and spicy foods. They may also suggest raising the head of your bed by 10 to 20cm, so your head and chest are higher than your waist. This will help stop stomach acid travelling up towards your throat.

If these lifestyle changes don’t work, you may be recommended a medicine like ranitidine.

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ranitidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at dosages up to 2,000 mg/kg/day.

Ranitidine was not mutagenic in standard bacterial tests (Salmonella, Escherichia coli) for mutagenicity at concentrations up to the maximum recommended for these assays.

In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for the next 9 weeks.

Ranitidine and breastfeeding

Ranitidine is safe to take while you’re breastfeeding. It passes into breast milk, but only in small amounts which aren’t harmful to the baby.

However, if your baby is premature or has health problems check with your doctor first.

Cautions with other medicines

For safety, tell your pharmacist or doctor if you’re taking other medicines including herbal remedies, vitamins or supplements.

Some medicines can interfere with ranitidine and make you more likely to have side effects.

Tell your doctor if you’re taking these medicines before you start taking ranitidine:

• anti-fungal medicines such as itraconazole, ketoconazole or posaconazole
• any medicine used to treat cancer
• HIV medicines

Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.

Procainamide: Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral ranitidine at a dose exceeding 300 mg per day.

Warfarin: There have been reports of altered prothrombin time among patients on concomitant warfarin and ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.

Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.

Atazanavir: Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.

Delavirdine: Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H2-receptor antagonists with delavirdine is not recommended.

Gefitinib: Gefitinib exposure was reduced by 44% with the coadministration of ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.

Glipizide: In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral ranitidine. Use appropriate clinical monitoring when initiating or discontinuing ranitidine.

Ketoconazole: Oral ketoconazole exposure was reduced by up to 95% when oral ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of ranitidine (150 mg twice daily) is unknown.

Midazolam: Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily. However, in another interaction trial in 8 volunteers receiving IV midazolam, a 300-mg oral dose of ranitidine increased midazolam exposure by about 9%. Monitor patients for excessive or prolonged sedation when ranitidine is coadministered with oral midazolam.

Triazolam: Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.

These are not all the medicines that may not mix well with ranitidine. For a full list see the leaflet inside your medicines packet.

Mixing ranitidine with herbal remedies and supplements

There isn’t enough research to know if complementary medicines and herbal remedies are safe to take with ranitidine.

What is ranitidine used for

Ranitidine is used to treat and prevent ulcers in the stomach and intestines. Ranitidine also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Ranitidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn and injury of the food pipe (esophagus).

Ranitidine is also used sometimes to treat upper gastrointestinal bleeding and to prevent stress ulcers, stomach damage from use of nonsteroidal anti-inflammatory drugs (NSAIDs), and aspiration of stomach acid during anesthesia. Talk to your doctor about the risks of using this medication for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Ranitidine reduces the amount of acid your stomach makes.

• Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Trials available to date have not assessed the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled comparative trials have been carried out for periods of longer than 1 year.
• The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).
• Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment has not been demonstrated. Trials available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric ulcer for periods of more than 6 weeks.
• Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled trials have been carried out for 1 year.
• Treatment of gastro-esophageal reflux disease (GERD). Symptomatic relief commonly occurs within 24 hours after starting therapy with Zantac 150 mg twice daily.
• Treatment of endoscopically diagnosed erosive esophagitis. Symptomatic relief of heartburn commonly occurs within 24 hours of therapy initiation with ranitidine 150 mg 4 times daily.
• Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.

Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; GERD; and erosive esophagitis.

Ranitidine is also taken to prevent and treat stomach ulcers.

Sometimes, ranitidine is taken for a rare illness caused by a tumor in the pancreas or gut called Zollinger-Ellison syndrome.

Ranitidine dose

Usual Adult Dose for Duodenal Ulcer

Oral

• Treatment dose: 150 mg orally 2 times a day OR 300 mg orally once a day after the evening meal or at bedtime
• Maintenance dose: 150 mg orally once a day at bedtime
• Duration of therapy: 8 weeks (treatment); up to 1 year (maintenance)

Parenteral:

IM or IV (bolus or intermittent infusion) Injection:

-Usual dose: 50 mg IM or IV every 6 to 8 hours
-Maximum dose: 400 mg/day

Continuous IV Infusion:

-Usual rate: 6.25 mg/hour

Comments:

• Patients may use antacids to treat pain.
• Both once or 2 times a day oral dosing regimens were shown to be effective in inhibiting gastric acid secretion.
• Injectable formulations do not require dilution when given as an IM injection.
• Intermittent IV bolus injections should be diluted up to 2.5 mg/mL and injected at a rate of up to 4 mL/min.
• Intermittent IV infusions should be diluted up to a concentration of 0.5 mg/mL and infused at a rate of up to 5 to 7 mL/min (approximately 15 to 20 minutes).
• Most patients receiving oral formulations heal within 4 weeks; there are no safety data for the treatment of uncomplicated duodenal ulcer beyond 8 weeks. Studies have not been conducted to assess safety in oral maintenance therapy longer than 1 year.
  

Uses:

• Short-term treatment of active duodenal ulcer
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers
• Some hospitalized patients with intractable duodenal ulcers

Usual Adult Dose for Dyspepsia

ORAL (OVER-THE-COUNTER FORMULATIONS):

• Symptom relief: 75 to 150 mg orally with a glass of water
• Symptom prevention: 75 to 150 mg orally with a glass of water 30 to 60 minutes before a meal
• Maximum dose: 2 tablets/day
• Duration of therapy: Up to 14 days (self-treatment)

Uses:

• Relief of heartburn associated with acid indigestion and sour stomach
• Relief of heartburn associated with acid indigestion and sour stomach brought on by eating/drinking certain foods and beverages

Usual Adult Dose for Erosive Esophagitis

ORAL:

• Treatment dose: 150 mg orally 4 times a day
• Maintenance dose: 150 mg orally 2 times a day
• Duration of therapy: Up to 48 weeks (maintenance)

Comments:

• Symptomatic relief usually starts within 24 hours of starting oral treatment.
• Placebo-controlled studies included use of maintenance doses for up to 48 weeks.

Use:

• Treatment of endoscopically diagnosed erosive esophagitis

Usual Adult Dose for Zollinger-Ellison Syndrome

ORAL:

• Initial dose: 150 mg orally 2 times a day
• Maximum dose: Up to 6 g/day

PARENTERAL:
Continuous IV Infusion:

-Initial rate: 1 mg/kg/hr
-Titration: After 4 hours, if gastric acid output is greater than 10 mEq/hr or the patient is symptomatic, the dose should be increased in 0.5 mg/kg/hr increments and acid levels should be re-measured
-Maximum dose: 2.5 mg/kg/hr
-Maximum rate: 220 mg/hr

Comment:
-Continuous IV infusions should be diluted to a concentration of 2.5 mg/mL or less.

Uses:

• Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, systemic mastocytosis)
• Alternative to oral formulations for short-term use in some hospitalized patients who are unable to take oral medications

Usual Adult Dose for Pathological Hypersecretory Conditions

ORAL:

• Initial dose: 150 mg orally 2 times a day
• Maximum dose: Up to 6 g/day

PARENTERAL:
Continuous IV Infusion:

-Initial rate: 1 mg/kg/hr
-Titration: After 4 hours, if gastric acid output is greater than 10 mEq/hr or the patient is symptomatic, the dose should be increased in 0.5 mg/kg/hr increments and acid levels should be re-measured
-Maximum dose: 2.5 mg/kg/hr
-Maximum rate: 220 mg/hr

Comment:
-Continuous IV infusions should be diluted to a concentration of 2.5 mg/mL or less.

Uses:

• Treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, systemic mastocytosis)
• Alternative to oral formulations for short-term use in some hospitalized patients who are unable to take oral medications

Usual Adult Dose for Gastroesophageal Reflux Disease (GERD)

ORAL:

• Usual dose: 150 mg orally 2 times a day

Comment:

Symptomatic relief usually starts within 24 hours of starting oral treatment.

Use:

Treatment of gastroesophageal reflux disease

Usual Adult Dose for Gastric Ulcer

ORAL:

• Treatment dose: 150 mg orally 2 times a day
• Maintenance dose: 150 mg orally once a day at bedtime

Comments:

Most patients heal within 6 weeks; there are no safety data for the treatment of uncomplicated, benign gastric ulcer beyond 6 weeks.

Uses:

Short-term treatment of active, benign gastric ulcer
Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers

Usual Pediatric Dose for Duodenal Ulcer

Less than 1 month AND with Extracorporeal membrane oxygenation:

PARENTERAL:
-2 mg/kg IV every 12 to 24 hours OR as a continuous infusion

1 month to 16 years:

ORAL:

• Treatment dose: 2 to 4 mg/kg orally 2 times a day
• Maximum treatment dose: 300 mg/day
• Maintenance dose: 2 to 4 mg/kg orally once a day
• Maximum maintenance dose: 150 mg/day

PARENTERAL:
-Usual dose: 2 to 4 mg/kg IV, divided and given every 6 to 8 hours OR as a continuous infusion
-Maximum dose: 50 mg/dose

16 years and older:

ORAL:

• Treatment dose: 150 mg orally 2 times a day OR 300 mg orally once a day after the evening meal or at bedtime
• Maintenance dose: 150 mg orally once a day at bedtime
• Duration of therapy: 8 weeks (treatment); up to 1 year (maintenance)

PARENTERAL:

IM or IV (bolus or intermittent infusion) Injection:
-Usual dose: 50 mg IM or IV every 6 to 8 hours
-Maximum dose: 400 mg/day

Continuous IV Infusion:
-Usual rate: 6.25 mg/hour

Comments:
-Patients younger than 1 month with ECMO who were given doses of 2 mg/kg had a gastric pH of greater than 4 for at least 15 hours.
-Placebo-controlled studies included use of maintenance doses for up to 48 weeks.
-Injectable formulations do not require dilution when given as an IM injection.
-Intermittent IV bolus injections should be diluted up to 2.5 mg/mL and injected at a rate of up to 4 mL/min.
-Intermittent IV infusions should be diluted up to a concentration of 0.5 mg/mL and infused at a rate of up to 5 to 7 mL/min (approximately 15 to 20 minutes).

Uses:

• Alternative to oral formulations for short-term use in some hospitalized patients who are unable to take oral medications
• Short-term treatment of active duodenal ulcer
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers
• Some hospitalized patients with intractable duodenal ulcers

Usual Pediatric Dose for Gastric Ulcer

Less than 1 month AND with Extracorporeal membrane oxygenation (ECMO):

PARENTERAL:

-2 mg/kg IV every 12 to 24 hours OR as a continuous infusion

1 month to 16 years:

ORAL:

• Treatment dose: 2 to 4 mg/kg orally 2 times a day
• Maximum treatment dose: 300 mg/day
• Maintenance dose: 2 to 4 mg/kg orally once a day
• Maximum maintenance dose: 150 mg/day

PARENTERAL:

-Usual dose: 2 to 4 mg/kg IV, divided and given every 6 to 8 hours OR as a continuous infusion
-Maximum dose: 50 mg/dose

16 years and older:

ORAL:

• Treatment dose: 150 mg orally 2 times a day OR 300 mg orally once a day after the evening meal or at bedtime
• Maintenance dose: 150 mg orally once a day at bedtime
• Duration of therapy: 8 weeks (treatment); up to 1 year (maintenance)

PARENTERAL:

IM or IV (bolus or intermittent infusion) Injection:

-Usual dose: 50 mg IM or IV every 6 to 8 hours
-Maximum dose: 400 mg/day

Continuous IV Infusion:

-Usual rate: 6.25 mg/hour

Comments:

• Patients younger than 1 month with extracorporeal membrane oxygenation who were given doses of 2 mg/kg had a gastric pH of greater than 4 for at least 15 hours.
• Placebo-controlled studies included use of maintenance doses for up to 48 weeks.
• Injectable formulations do not require dilution when given as an IM injection.
• Intermittent IV bolus injections should be diluted up to 2.5 mg/mL and injected at a rate of up to 4 mL/min.
• Intermittent IV infusions should be diluted up to a concentration of 0.5 mg/mL and infused at a rate of up to 5 to 7 mL/min (approximately 15 to 20 minutes).

Uses:

• Alternative to oral formulations for short-term use in some hospitalized patients who are unable to take oral medications
• Short-term treatment of active duodenal ulcer
• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers
• Some hospitalized patients with intractable duodenal ulcers

Usual Pediatric Dose for Gastroesophageal Reflux Disease

1 month to 16 years:

ORAL:

Usual dose: 5 to 10 mg/kg/day orally, given in 2 divided doses

16 years and older:

ORAL:

Usual dose: 150 mg orally 2 times a day

Comments:

Symptomatic relief usually starts within 24 hours of starting oral treatment.
Placebo-controlled studies included use of maintenance doses for up to 48 weeks.

Use:

Treatment of gastroesophageal reflux disease

Usual Pediatric Dose for Erosive Esophagitis

1 month to 16 years:

ORAL:

Usual dose: 5 to 10 mg/kg/day, given in 2 divided doses

16 years and older:

ORAL:

• Treatment dose: 150 mg orally 4 times a day
• Maintenance dose: 150 mg orally 2 times a day
• Duration of therapy: Up to 48 weeks (maintenance)

Comments:

• Symptomatic relief usually starts within 24 hours of starting oral treatment.
• Placebo-controlled studies included use of maintenance doses for up to 48 weeks.

Use:

Treatment of endoscopically diagnosed erosive esophagitis

Usual Pediatric Dose for Dyspepsia

12 years and older:

ORAL (OVER-THE-COUNTER FORMULATIONS):

• Symptom relief: 75 mg orally with a glass of water
• Symptom prevention: 75 mg orally with a glass of water 30 to 60 minutes before a meal
• Maximum dose: 150 mg/day
• Duration of therapy: Up to 14 days (self-treatment)

Uses:

• Relieve heartburn associated with acid indigestion and sour stomach
• Relieve heartburn associated with acid indigestion and sour stomach brought on by eating/drinking certain foods and beverages

Renal Dose Adjustments

Creatinine Clearance less than 50 mL/min:

Oral: 150 mg orally every 24 hours. The frequency of dosing may be increased with caution.

Parenteral:

• IM/IV: 50 mg IM/IV every 18 to 24 hours. The frequency of dosing may be increased to every 12 hours (or further) with caution.
• Continuous infusion: Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Elderly patients: Since elderly patients are more likely to have decreased renal function, dose selection should be made cautiously, and an increased frequency of renal function monitoring should be considered.

How and when to take ranitidine

It’s usual to take ranitidine twice a day – 1 dose in the morning and 1 dose in the evening. Some people only need to take ranitidine once a day, at bedtime.

Very young babies, and people with Zollinger-Ellison syndrome, usually take ranitidine 3 times a day. People with severe inflammation of the food pipe (esophagitis) may need to take it 4 times a day.

How to take ranitidine

Take ranitidine exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Your doctor may recommend an antacid to help relieve pain. Carefully follow your doctor’s directions about the type of antacid to use, and when to use it.

You can take ranitidine with or without food. However, if you get symptoms whenever you eat or drink, take your medicine 30 minutes to 60 minutes before having a drink, snack or meal.

• Tablets – swallow tablets whole with a glass of water, milk or juice.
• Soluble tablets – dissolve tablets in half a glass of water. Do not use milk, fizzy water or other fizzy drinks. Wait until the medicine has completely dissolved and then drink it straight away.
• Liquid – this comes with a syringe or spoon to help you measure it. If you don’t have a syringe or spoon, ask your pharmacist for one. Do not use a kitchen teaspoon as it won’t give you the right amount.

Liquid ranitidine is suitable for children and people who find it difficult to swallow tablets.

Do not crush, chew, or break the ranitidine effervescent tablet, and do not allow it to dissolve on your tongue. The 25-milligram effervescent tablet must be dissolved in at least 1 teaspoon of water before swallowing. The150-milligram effervescent tablet should be dissolved in 6 to 8 ounces of water.

Allow the ranitidine effervescent tablet to dissolve completely in the water, and then drink the entire mixture. If you are giving this medicine to a child, you may draw the liquid mixture into a medicine dropper and empty the dropper into the child’s mouth.

Ranitidine granules should be mixed with 6 to 8 ounces of water before drinking.

Measure ranitidine liquid with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

It may take up to 8 weeks before your ulcer heals. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 6 weeks of treatment.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using ranitidine.

Store ranitidine at room temperature away from moisture, heat, and light.

Active Duodenal Ulcer:

The current recommended adult oral dosage of ranitidine for duodenal ulcer is 150 mg twice daily. An alternative dosage of 300 mg once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared with the other in a particular patient population have yet to be demonstrated. Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US trials, and several foreign trials have shown that 100 mg twice daily is as effective as the 150-mg dose.

Antacid should be given as needed for relief of pain.

Maintenance of Healing of Duodenal Ulcers:

The current recommended adult oral dosage is 150 mg at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome):

The current recommended adult oral dosage is 150 mg twice daily. In some patients it may be necessary to administer ranitidine 150-mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer:

The current recommended adult oral dosage is 150 mg twice daily.

Maintenance of Healing of Gastric Ulcers:

The current recommended adult oral dosage is 150 mg at bedtime.

Gastro-esophageal reflux disease (GERD):

The current recommended adult oral dosage is 150 mg twice daily.

Erosive Esophagitis:

The current recommended adult oral dosage is 150 mg 4 times daily.

Maintenance of Healing of Erosive Esophagitis:

The current recommended adult oral dosage is 150 mg twice daily.

Pediatric Use:

The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of ranitidine in neonatal patients (aged younger than 1 month) to make dosing recommendations.

The following 3 subsections provide dosing information for each of the pediatric indications.

• Treatment of Duodenal and Gastric Ulcers: The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical trials and pharmacokinetic data in pediatric patients.
• Maintenance of Healing of Duodenal and Gastric Ulcers: The recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day. This recommendation is derived from adult clinical trials and pharmacokinetic data in pediatric patients.
• Treatment of GERD and Erosive Esophagitis: Although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg/day, usually given as 2 divided doses.

Dosage Adjustment for Patients with Impaired Renal Function:

On the basis of experience with a group of subjects with severely impaired renal function treated with ranitidine, the recommended dosage in patients with a creatinine clearance <50 mL/min is 150 mg every 24 hours. Should the patient’s condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function.

Will my dose go up or down?

Sometimes your doctor will increase your dose of ranitidine if it isn’t working well enough.

Depending on the reason you take ranitidine, you may take a higher dose to start with – usually for at least 1 month. After this, your doctor may recommend a lower dose.

What if I forget to take ranitidine?

If you usually take it:

• once a day, take the missed dose as soon as you remember, unless it’s less than 12 hours until your next dose – in which case skip the missed dose
• twice a day, take the missed dose as soon as you remember, unless it’s nearly time for your next dose – in which case skip the missed dose
• 3 or 4 times a day, skip the missed dose and take your next dose as normal

Do NOT take a double dose to make up for a forgotten dose.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to remember your medicine.

What if I take too much ranitidine?

Ranitidine is generally very safe. Taking too much is unlikely to harm you or your child.

If you take an extra dose by mistake, you might get some side effects, such as feeling sick. Call your doctor if you’re worried, or you’re bothered by side effects.

Ranitidine side effects

Most people who take ranitidine do not have any side effects. If you do get a side effect, it is usually mild and will go away when you stop taking ranitidine.

The following side effects aren’t common and may happen in more than 1 in 1,000 people. Talk to your doctor or pharmacist if these side effects bother you or don’t go away:

• stomach pains
• constipation
• feeling sick (nausea)
• headache
• diarrhea
• vomiting

Ranitidine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

These are not all the side effects of ranitidine. For a full list see the leaflet inside your medicines packet.

The following have been reported as events in clinical trials or in the routine management of patients treated with ranitidine. The relationship to therapy with ranitidine has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of ranitidine.

Central Nervous System

Rarely, malaise, dizziness, somnolence, insomnia, and vertigo. Rare cases of reversible mental confusion, agitation, depression, and hallucinations have been reported, predominantly in severely ill elderly patients. Rare cases of reversible blurred vision suggestive of a change in accommodation have been reported. Rare reports of reversible involuntary motor disturbances have been received.

Cardiovascular

As with other H2-blockers, rare reports of arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats.

Gastrointestinal

Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis.

Hepatic

There have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has occurred. Rare cases of hepatic failure have also been reported. In normal volunteers, SGPT values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg intravenously 4 times daily for 7 days, and in 4 of 24 subjects receiving 50 mg intravenously 4 times daily for 5 days.

Musculoskeletal

Rare reports of arthralgias and myalgias.

Hematologic

Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported.

Endocrine

Controlled studies in animals and man have shown no stimulation of any pituitary hormone by ranitidine and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ranitidine has been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving ranitidine, but the incidence did not differ from that in the general population. Rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females.

Integumentary

Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.

Respiratory

A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-receptor antagonists (H2RAs) compared with patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63. However, a causal relationship between use of H2RAs and pneumonia has not been established.

Other

Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.

Serious side effects

Serious side effects are very rare and happen in less than 1 in 10,000 people. Call a doctor straight away if you have:

• stomach pain that seems to be getting worse – this can be a sign of an inflamed liver or pancreas
• back pain, fever, pain when peeing or blood in your pee – these can be signs of kidney problems
• a rash, swollen joints or kidney problems – these can be signs that your small blood vessels are swollen (vasculitis)
• a slow or irregular heartbeat

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction to ranitidine.

• A serious allergic reaction is an emergency. Contact a doctor straight away if you think you or someone around you is having a serious allergic reaction.

The warning signs of a serious allergic reaction are:

• getting a skin rash that may include itchy, red, swollen, blistered or peeling skin
• wheezing
• tightness in the chest or throat
• having trouble breathing or talking
• swelling of the mouth, face, lips, tongue or throat

How to cope with side effects

What to do about:

• stomach pains – try to rest and relax. It can help to eat and drink slowly and have smaller and more frequent meals. Putting a heat pad or covered hot water bottle on your tummy may also help. If you are in a lot of pain, speak to your pharmacist or doctor.
• constipation – eat more high-fiber foods such as fresh fruit and vegetables and cereals, and drink plenty of water. Try to exercise more regularly, for example, by going for a daily walk or run. If this doesn’t help, talk to your pharmacist or doctor.
• feeling sick – it may help if you don’t eat rich or spicy food while you’re taking ranitidine.

Human Toxicity Reports

Headache (sometimes severe) occurs in approx 3% of patients receiving the drug ². Malaise, dizziness, somnolence, insomnia, and vertigo have been reported less frequently. Reversible mental confusion, agitation, mental depression, and hallucinations have occurred, mainly in debilitated geriatric patients. A child who was receiving prolonged, high-dose oral ranitidine therapy (8 mg/kg once daily for 10 months) developed altered consciousness, drowsiness, dysarthria, hyporeflexia, positive Babinski’s sign, diaphoresis, and bradycardia, which resolved within 24 hr after discontinuance of the drug.

Constipation, nausea, vomiting, and abdominal discomfort or pain have occurred in patients receiving ranitidine. Pancreatitis has been reported rarely ².

Rash, which may be urticarial, maculopapular, and/or pruritic, has been reported during ranitidine therapy ². Rash suggestive of mild erythema multiforme has occurred rarely. Urticaria at the site of injection has occurred following IV admin of ranitidine. Alopecia has occurred rarely ².

Leukopenia, granulocytopenia, agranulocytosis, thrombocytopenia, aplastic anemia, acquired immune hemolytic anemia, and pancytopenia, which may be accompanied by bone marrow hypoplasia, have been reported rarely in patients receiving ranitidine ². Alterations in blood cell counts usually were reversible. At least one case of leukocytosis has been reported 6-8 days after initiating ranitidine therapy, which resolved following discontinuance ². Aplastic anemia has occurred in at least one patient receiving ranitidine ².

Small increases in serum creatinine, without concomitant increases in BUN, have been reported during ranitidine therapy ². Increases in serum aminotransferase, alkaline phosphatase, LDH, total bilirubin, and gamma-glutamyl transferase concentration have been reported and reversible hepatitis, which may be hepatocellular, hepatocanalicular, or both and may or may not be accompanied by jaundice, has occurred occasionally in individuals receiving ranitidine and usually was reversible; however, death has been reported rarely ².

A 63 yr old woman developed anicteric hepatitis after two wk of therapy with ranitidine ³. Despite continuation of therapy, her symptoms resolved within 5 days and transaminase levels returned to normal in the next 4 weeks, at which time use of the drug ceased. No other cause for the reaction could be found ³.

Cardiac arrhythmias have occurred rarely in patients receiving ranitidine ². Bradycardia, sometimes assoc with dyspnea, has occurred ². Tachycardia, AV block, asystole, and ventricular premature complexes have also been reported rarely ².

Arthralgias, myalgias, and hypersensitivity reactions such as bronchospasm, fever, rash, and eosinophilia have occurred rarely in patients receiving ranitidine ². Anaphylaxis, characterized by severe urticaria and a decrease in blood pressure in one patient following administration of a single dose of ranitidine, has occurred rarely; exacerbation of asthma and angioedema also has occurred ². Mild erythema multiforme-like rash and alopecia also have occurred rarely. Rare reports suggest that ranitidine may precipitate acute attacks of porphyria in patients with acute porphyria; therefore, the drug should be avoided in patients with a history of acute porphyria ².

In a study of 51 male patients with duodenal ulcer, treatment with ranitidine, produced no decrease in basal levels of serum testosterone, as did cimetidine ⁴.

Ranitidine inhibited in a dose-dependent manner acetylcholinesterases from human erythrocytes and gastric mucosa ⁵. Pseudocholinesterase in serum was also inhibited, the levels required were about 25 times higher. A stimulation of cholinergic mechanisms in ranitidine treatment should occur, e.g, stimulation of glandular secretion or increase of gastrointestinal motility ⁵.

Symptoms of acute intoxication with both cimetidine and ranitidine are bradycardia and tachycardia ⁶; CNS disturbances, including confusion, delirium, drowsiness, slurred speech, flushing, and sweating; dermatologic lesions; endocrine abnormalities; GI disorders; and liver dysfunction ⁶.

Most controlled studies in humans indicate that ranitidine does not alter theophylline metabolism, even at high doses ⁷. However, there have been several case reports published recently which demonstrate the development of theophylline toxicity mostly in older patients receiving stable oral doses of this drug when ranitidine was administered simultaneously ⁷. A study involving eleven elderly (mean age, 69.0 + or – 6.2 years) patients with chronic obstructive pulmonary disease (COPD). During one week the patients took slow-release theophylline, 200 mg every 12 hr, followed by one week intake of the same dose of theophylline plus ranitidine tablets, 150 mg every 12 hr. At the end of each period, blood samples were obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 hr after the morning dose for the determination of serum theophylline levels. The peak theophylline concentration (Tmax) was achieved after 4.1 + or – 0.9 hr while the patients were taking theophylline, and after 2.9 + or – 1.4 hr with the combined regimen. This difference was statistically significant. In only 3/11 subjects did Tmax remain unchanged during both phases of the study. The mean theophylline clearance rates while the patients were receiving theophylline alone (39.58 + or – 19.89 ml/min) and when they were receiving both medications 134.42 + or – 10.55 ml/min) were similar. The mean serum levels while the patients were receiving theophylline alone were slightly higher but not statistically different. These results suggest that the reported increases in serum theophylline levels in older patients receiving theophylline and ranitidine cannot be ascribed to slower theophylline metabolism in the geriatric patients with chronic obstructive pulmonary disease who is also given ranitidine ⁷.

A case report of acute cholestatic hepatitis associated with rash and hypereosinophilia, in which the absence of transfusion, intercurrent viral infection, alcohol consumption or other hepatotoxic drugs are suggestive of ranitidine-induced hepatotoxicity ⁸. The pathogenesis of the disorder is unknown, but the lack of a dose-effect relationship, the rarity and unpredictability of the reaction, as well as the clinical signs suggest that hypersensitivity is involved. Physicians should be aware of this rare and idiosyncratic side-effect of ranitidine ⁸.

Although acute interstitial nephritis has been well described with the histamine H2-receptor antagonist cimetidine, a study authors found only one previous case report of ranitidine-induced interstitial nephritis in the literature ⁹. They describe an additional patient who developed acute interstitial nephritis after taking ranitidine ⁹. Electron microscopy showed focal fusion of the epithelial cell foot processes that was not described in the previous report of ranitidine-induced interstitial nephritis.

Reversible hematologic abnormalities including hemolytic anemia ¹⁰ with a positive direct Coombs’ test have been associated with ranitidine. In addition to the case report cited above, the US Food and Drug Administration had received five other cases of hemolysis associated with recent intake of ranitidine as of February 1991 ¹⁰. To investigate the possible association of ranitidine with autoimmune hemolytic anemia, a study was conducted to determine how often diagnoses of hemolytic anemia or abnormal Coombs’ test results followed dispensing of ranitidine using the automated medical and pharmacy records of a large health maintenance organization. No occurrences of hemolytic anemia were identified among 12,054 individuals following 38,686 prescriptions for this medication. The 95% upper confidence bound was 3.1 cases/10,000 exposed persons. One abnormal direct Coombs test with mild anemia was discovered during routine prenatal testing of an asymptomatic patient who was dispensed ranitidine two and a half months previously. Hemolysis, however, was not demonstrated and an association with prior ranitidine use could not be confirmed. Additional analyses indicate that in only 30% of ranitidine courses was a blood count obtained. In those courses with hematocrits below 40%, less than 1% had a Coombs’ test performed. Chart review suggests that the majority of individuals with severe anemia have alternative explanations other than autoimmune hemolysis for their anemia ¹⁰. This analysis indicates that ranitidine is unlikely to be a common cause of clinically recognized autoimmune hemolytic anemia and demonstrates the utility of large automated medical and pharmacy data bases to conduct post-marketing studies of spontaneously reported drug effects.

Ranitidine overdose

Ranitidine overdose occurs when someone takes more than the normal or recommended amount of this medicine. This can be by accident or on purpose.

There has been limited experience with overdosage. Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience. In addition, abnormalities of gait and hypotension have been reported.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Symptoms of an ranitidine overdose are:

• Abnormal heartbeat, including rapid or slow heartbeat
• Drowsiness, confusion
• Diarrhea
• Difficulty breathing
• Dilated pupils
• Flushing
• Low blood pressure
• Nausea, vomiting
• Slurred speech
• Sweating

Seek medical help right away. DO NOT make the person throw up unless poison control or a health care provider tells you to.

When overdosage occurs, the usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.

Studies in dogs receiving dosages of ranitidine in excess of 225 mg/kg/day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD50 values in mice and rats were 77 and 83 mg/kg, respectively.

What to Expect at the Emergency Room

Take the container with you to the hospital, if possible.

The provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure. Symptoms will be treated. The person may receive:

• Activated charcoal
• Blood and urine tests
• Breathing support, including oxygen
• Chest x-ray
• ECG (electrocardiogram, or heart tracing)
• Intravenous fluids (through a vein)
• A laxative
• Medicine to treat symptoms
• Tube through the mouth into the stomach to empty the stomach (gastric lavage)

Outlook (Prognosis)

Serious complications are rare. These are generally safe medicines, even when taken in large doses.

References

1. McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2184
2. McEvoy G.K. (ed.). American Hospital Formulary Service-Drug Information 96. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1996 (Plus Supplements)., p. 2182
3. Barr GD, Piper DW; Med J Aust 2 (8): 421; 1981 https://www.ncbi.nlm.nih.gov/pubmed/6275248
4. Peden NR et al; Acta Endocrinol (Copenh) 96 (4): 564-8;1981 http://www.eje-online.org/content/96/4/564.long
5. Hansen WE, Bertl S; Z Gastroenterol 21 (4): 164-7;1983 https://www.ncbi.nlm.nih.gov/pubmed/6306938
6. Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 824
7. Cukier A et al; Braz J Med Biol Res 28 (8): 875-9;1995 https://www.ncbi.nlm.nih.gov/pubmed/8555989
8. Devuyst C et al; Acta Clin Belg 48 (2): 109-14;1993 https://www.ncbi.nlm.nih.gov/pubmed/8392242
9. Gaughan WJ et al; Am J Kidney Dis 22 (2): 337-40;1993 https://www.ncbi.nlm.nih.gov/pubmed/8352263
10. Choo PW et al; J Clin Epidemiol 47 (lO): 1175-9; 1994 ttps://www.ncbi.nlm.nih.gov/pubmed/7722551