Colesevelam

Colesevelam also known as colesevelam hydrochloride, is a nonabsorbed bile acid sequestrant that is used a therapy of high cholesterol in adults and children at least 10 years old and for the pruritus of chronic liver disease and biliary obstruction. Colesevelam lowers “bad” cholesterol in the blood, which is also called LDL (low-density lipoprotein) cholesterol. Lowering your LDL cholesterol may reduce your risk of hardened arteries, which can lead to heart attacks, stroke, and circulation problems. Colesevelam is also used to improve blood sugar control in adults with type 2 diabetes. LDL-cholesterol and hemoglobin (Hb)A1c were shown to be reduced in three double-blind, placebo-controlled trials with the use of colesevelam hydrochloride in type 2 diabetic patients ¹. These results led to the U.S. Food and Drug Administration (FDA) approval of colesevelam as an adjuvant to exercise and dietary restriction for improving glycemic control in patients with type 2 diabetes. Therefore, colesevelam therapy is effective for patients with type 2 diabetes who have not met their HbA1c goal of below 7% or LDL  “bad” cholesterol goal of under 100 mg/dL or 30 to 49 % or over 50 % reduction in LDL “bad” cholesterol ². The main advantage of using bile acid sequestrants is that it can safely be administered in combination with other anti-diabetic medications and statins. They are the safest LDL “bad” cholesterol lowering therapy to date.

Colesevelam is sometimes used together with “statin” (HMG-CoA reductase inhibitors) cholesterol medications such as atorvastatin, lovastatin, simvastatin, Crestor, Lipitor, Pravachol, Zocor, and others.

Colesevelam is not for treating type 1 diabetes.

Colesevelam was approved for use in the United States in 2000 and is currently used largely as an adjunctive therapy when statins or other lipid lowering agents result in an inadequate decrease in cholesterol levels. Colesevelam is also approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes. Colesevelam is available in tablets of 625 mg under the brand name of Welchol. The tablets are usually taken once or twice a day with meals and a beverage. The usual dose is three tablets twice a day, given with meals or six tablets once daily. Other drugs should be given 1 hour before or 4 to 6 hours after colesevelam. Colesevelam is administered in tablet form and does not have the problem of lack of palatability that is characteristic of other bile acid resins. Colesevelam also comes in a chewable bar, and as a powder to be mixed with a liquid to take by mouth. The chewable bars and the powder are usually taken once a day with a meal. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take colesevelam exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are taking the powder for oral suspension, empty the entire contents of 1 packet into a glass. Add 8 ounces of water, fruit juice, or a diet soft drink. Stir well and drink the entire contents of the glass. It is normal for the contents to appear cloudy and not fully dissolve. Do not take the powder in its dry form.

If you are taking the chewable bars, you should know that the chewable bars contain 80 calories per bar.

Colesevelam controls your condition but does not cure it. Continue to take colesevelam even if you feel well. Do not stop taking colesevelam without talking to your doctor.

Your doctor may want to measure the cholesterol levels in your blood on a regular basis to make sure colesevelam is working properly. Be sure to keep all of your appointments. You will also need to check your blood sugar regularly at home.

Do not stop using colesevelam without first checking with your doctor. When you stop using colesevelam, your blood cholesterol and sugar levels may increase again.

Colesevelam side effects include abdominal discomfort, indigestion, nausea, flatuence and constipation.

Colesevelam can cause low blood sugar (hypoglycemia). The symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). People may feel different symptoms with a low blood sugar. It is important that you learn which symptoms you get when your blood sugar is low. The symptoms of low blood sugar include: anxiety, behavior change similar to being drunk, blurred vision, cold sweats, confusion, cool, pale skin, difficulty with thinking, drowsiness, excessive hunger, a fast heartbeat, continuing headache, nausea, nervousness, nightmares, restless sleep, shakiness, slurred speech, and unusual tiredness or weakness.

If you have any symptoms of low blood sugar, check your blood sugar level right away. If needed, you can eat glucose tablets or gel, corn syrup, honey, or sugar cubes, or you can drink fruit juice, a non-diet soft drink, or sugar dissolved in water.

Check with your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness. These may be symptoms of acute pancreatitis.

Colesevelam can cause constipation, and for some people this can be very uncomfortable. If you have problems with severe constipation while using colesevelam, talk to your doctor.

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.

Colesevelam mechanism of action

Colesevelam is in a class of medications called bile acid sequestrants. It works by binding bile acids in your intestines to form a product that is removed from the body. Bile acids are made when cholesterol is broken down in your body. Removing these bile acids helps to lower your blood cholesterol. Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats may help prevent heart disease, angina (chest pain), strokes, and heart attacks.

Colesevelam is a large, highly positively charged anion exchange resin that binds to negatively charged anions such as bile acids (as well as other organic compounds and some medications) ³. The binding of bile acids to colesevelam creates an insoluble compound that cannot be reabsorbed and is thus excreted in the feces. Bile acids ordinarily undergo extensive (>95%) enterohepatic recirculation, being secreted in bile, acting as fat solubilizing compounds in the upper intestine, and then being reabsorbed in the distal small bowel. Chronic loss of bile acids results in a contraction in the total bile acid pool. The liver compensates for this decrease by increasing bile acid synthesis, which directly competes with cholesterol synthesis resulting in a decrease in serum levels. Some of the decrease in serum cholesterol may also result from inhibition of fat absorption by the binding of bile acids to colesevelam.

Colesevelam uses

Colesevelam is used in adults along with diet, weight loss, and exercise to reduce the amount of cholesterol and certain fatty substances in the blood alone or in combination with other cholesterol-lowering medications known as HMG-CoA reductase inhibitors (statins). Colesevelam is also used alone or in combination with statins (HMG-CoA reductase inhibitors) in certain boys and in girls, ages 10 to 17, with familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally) to decrease the amount of cholesterol and other fatty substances in the blood.

Colesevelam is also used along with diet and exercise to control blood sugar levels in adults with type 2 diabetes (condition in which the body does not use insulin normally and therefore cannot control the amount of sugar in the blood).

Colesevelam special precautions

Before taking colesevelam:

• tell your doctor and pharmacist if you are allergic to colesevelam or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the following: anticoagulants such as warfarin and metformin extended-release (Glucophage XR, Glumetaza).
• if you are taking cyclosporine (Gengraf, Neoral, Sandimmune),, glipizide (Glucotrol), glimepride (Amaryl), glyburide (Diabeta), levothyroxine (Synthroid), olmesartan (Benicar), oral contraceptives (birth control pills), phenytoin (Dilantin), or vitamins, take them at least 4 hours before colesevelam.
• tell your doctor if you have or have ever had a blockage in your stomach or intestines, high levels of triglycerides (fatty substance) in the blood, or swelling of the pancreas caused by high levels of triglycerides in the blood. Your doctor will probably tell you not to take colesevelam.
• tell your doctor if you have had gastrointestinal surgery, and if you have or have ever had any problem with the ability to digest or absorb nutrients from food, any type of stomach problem such as slow stomach emptying, or difficulty swallowing.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking colesevelam, 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 the powder for oral suspension contains aspartame that forms phenylalanine.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to colesevelam 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.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of colesevelam in children 10 years of age and older. However, safety and efficacy of colesevelam in children younger than 10 years of age or in girls before having their first menstrual period have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of colesevelam in the elderly. However, elderly patients are more sensitive to the effects of colesevelam than younger adults.

Breastfeeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Colesevelam 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 colesevelam, 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 colesevelam 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.

• Bezafibrate
• Deferasirox
• Mycophenolate Mofetil
• Mycophenolic Acid
• Pravastatin

Using colesevelam 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.

• Cyclosporine
• Desogestrel
• Dienogest
• Drospirenone
• Estradiol Cypionate
• Estradiol Valerate
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Glimepiride
• Glipizide
• Glyburide
• Levonorgestrel
• Levothyroxine
• Medroxyprogesterone Acetate
• Mestranol
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Olmesartan Medoxomil
• Phenytoin
• Warfarin

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 colesevelam. Make sure you tell your doctor if you have any other medical problems, especially:

• Bowel blockage, history of or
• Hypertriglyceridemia (high triglycerides or fatty acids in the blood), severe or
• Pancreatitis (swelling of the pancreas) caused by hypertriglyceridemia, history of—Should not be used in patients with these conditions.
• Diabetic ketoacidosis (high ketones and acid in the blood) or
• Type 1 diabetes—Should not be used in patients with these conditions. Your doctor must give you insulin to treat these conditions.
• Dysphagia (trouble swallowing) or
• Esophageal blockage (problem with swallowing) or
• Vitamin deficiency (eg, vitamin A, D, E, or K) or history of—Use with caution. May make these conditions worse.
• Gastrointestinal motility disorder (eg, chronic constipation) or
• Gastrointestinal surgery, major and recent (eg, colostomy) or
• Gastroparesis (bowels move slowly) or
• Malabsorption syndrome (food not absorbed in the stomach or bowels)—Use is not recommended. May cause side effects to become worse.
• Phenylketonuria (PKU)—The powder for oral suspension contains phenylalanine, which can make this condition worse.

Colesevelam dose

The dose of colesevelam 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 colesevelam. 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.

Adult dose for hyperlipidemia

Uses: As an adjunct to diet and exercise to reduce elevated low density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia.

Dose: 3.75 g orally/day; may take as follows:

• Oral Tablets:
  • Once-daily dosing regimen: 3.75 g (six 625 mg tablets) orally once a day
  • Twice-daily dosing regimen: 1.875 g (three 625 mg tablets) orally twice a day
• Oral Suspension: 3.75 g packet orally once a day
• Chewable Bar: 3.75 g bar orally once a day

Comments:

• Colesevelam may be dosed at the same time as a statin or dosed apart; lipid levels should be monitored within 4 to 6 weeks of initiating this drug.
• Colesevelamg has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.

Adult dose for diabetes type 2

Uses: As an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Dose: 3.75 g orally/day; may take as follows:

• Oral Tablets:
  • Once-daily dosing regimen: 3.75 g (six 625 mg tablets) orally once a day
  • Twice-daily dosing regimen: 1.875 g (three 625 mg tablets) orally twice a day
• Oral Suspension: 3.75 g packet orally once a day
• Chewable Bar: 3.75 g bar orally once a day

Comments:

• Colesevelam may be dosed at the same time as a statin or dosed apart; lipid levels should be monitored within 4 to 6 weeks of initiating this drug.
• Colesevelam has not been studied in combination with a dipeptidyl peptidase 4 inhibitor.
• Colesevelam should not be used for the treatment of type 1 diabetes or the treatment of diabetic ketoacidosis.

Pediatric dose for heterozygous familial hypercholesterolemia

Use: As an adjunct to diet and exercise to reduce elevated low density lipoprotein cholesterol (LDL-C) in boys and postmenarchal girls 10 years or older with primary hyperlipidemia.

For boys and postmenarchal girls 10 years or older:

• 3.75 g orally/day; may take as follows:
  • Oral Suspension: 3.75 g packet orally once a day
  • Chewable Bar: 3.75 g bar orally once a day

Comments:

• Due to tablet size, the oral suspension is recommended in the pediatric population.
• Colesevelam may be dosed at the same time as a statin or dosed apart; lipid levels should be monitored within 4 to 6 weeks of initiating this drug.
• The safety and efficacy of colesevelam was evaluated in pediatric patients with heterozygous familial hypercholesterolemia (HeFH) taking a stable statin dose (with LDL-C greater than 130 mg/dL) or naive to lipid-lowering therapy (with LDL-C greater than 160 mg/dL).

Renal dose adjustments

• No adjustment recommended

Liver dose adjustments

• No adjustment recommended.

What should I do if I forget a dose?

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 dose.

Colesevelam side effects

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

More common adverse effects:

• fever
• headache
• muscle aches
• sore throat
• unusual tiredness or weakness

Less common adverse effects:

• anxiety
• blurred vision
• body aches or pain
• chills
• cold sweats
• confusion
• cool, pale skin
• cough
• depression
• diarrhea
• difficulty in breathing
• difficulty in moving
• dizziness
• dry throat
• ear congestion
• general feeling of discomfort or illness
• hoarseness
• increased hunger
• joint pain or swelling
• loss of appetite
• loss of consciousness
• loss of voice
• muscle pains, cramps, or stiffness
• nausea
• nervousness
• nightmares
• pounding in the ears
• seizures
• shakiness
• shivering
• slow or fast heartbeat
• slurred speech
• sneezing
• stuffy or runny nose
• sweating
• tender, swollen glands in the neck
• trouble with sleeping
• trouble with swallowing
• voice changes
• vomiting

Incidence not known

• bleeding after defecation
• bloating
• constipation
• dark urine
• full or bloated feeling
• pain or discomfort in the chest
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pressure in the stomach
• severe stomach pain
• swelling of the abdominal or stomach area
• unable to swallow saliva
• uncomfortable swelling around the anus
• yellow eyes or skin

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

• belching
• bloating
• heartburn
• stomach discomfort, upset, or pain

Less common

• accidental injury
• back pain
• lack or loss of strength

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional. Call your doctor for medical advice about side effects.

References

1. Lent-Schochet D, Jialal I. Antilipemic Agent Bile Acid Sequestrants. [Updated 2019 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549906
2. Jialal I, Abby SL, Misir S, Nagendran S. Concomitant reduction in low-density lipoprotein cholesterol and glycated hemoglobin with colesevelam hydrochloride in patients with type 2 diabetes: a pooled analysis. Metab Syndr Relat Disord. 2009 Jun;7(3):255-8.
3. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Colesevelam. [Updated 2017 Sep 28]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548873