What are opioids

Opioids also known as prescription opioids, narcotics or pain killers (narcotic analgesics), are a large class of medications related in structure to the natural plant alkaloids found in opium that are derived from the resin of the opium poppy, Papaver somniferum. The natural alkaloids are also referred to as opiates and include morphine and codeine. Synthetic derivatives include heroin, fentanyl, hydromorphone, methadone, buprenorphine and others. If a narcotic analgesic is deemed appropriate, codeine or tramadol should be tried first if the pain is mild-to-moderate. If the pain is unresponsive to these analgesics, or for more severe pain, then hydromorphone, morphine, or oxycodone should be considered. Fentanyl and methadone should only be used for severe pain that is unresponsive to other narcotic analgesics. Buprenorphine and methadone are the most frequently dispensed opioids worldwide ¹. Buprenorphine and methadone are chosen due to their safety and long duration of action, and only one administration daily is needed ². Not all opioids are prescription drugs. Heroin is considered a highly addictive and illegal opiate drug and is classified as a Schedule I drug under the Controlled Substances Act of 1970. Heroin carries strong criminal penalties and has no accepted medical use in the United States as determined by the Drug Enforcement Administration (DEA).

Opioid medications may be used short-term to ease the discomfort from conditions such as a broken bone or after surgery, or for long-term pain (chronic pain) such as cancer. Opioids are also used in cough medications (codeine or hydrocodone), in medicines for diarrhea and even to help combat opioid addiction itself. They can also be used in combination with other medications, such as acetaminophen or ibuprofen, for added pain relief. There are risks, though, when opioid medications are used incorrectly most have a high potential for dependency and abuse. Misuse of opiates can lead to opioid dependence, addiction, and in some situations, overdose, which can be fatal. According to the National Institute on Drug Abuse, over 70,000 Americans died from drug-involved overdose in 2019, including illicit drugs and prescription opioids ³. Because of this risk, as well as the risk of diversion, opioids are classified as controlled substances in the U.S. The misuse of and addiction to opioids—including prescription pain relievers, heroin, and synthetic opioids such as fentanyl—is a serious national crisis that affects public health as well as social and economic welfare. The Centers for Disease Control and Prevention (CDC) estimates that the total “economic burden” of prescription opioid misuse alone in the United States is $78.5 billion a year, including the costs of healthcare, lost productivity, addiction treatment, and criminal justice involvement ⁴.

Opioids work on your central nervous system (brain and spinal cord) to slow down nerve signals between your brain and your body. This can reduce feelings of pain, but it can also produce side effects, ranging from constipation to dangerous slowing down of a person’s breathing.

Opioids can also increase the production of the hormone dopamine in the brain. Dopamine can produce feelings of pleasure and pain relief.

Opioids have a variety of clinical effects, but are predominantly known and used for their profound pain relieving effects. Other effects that are often linked to opiate analgesia include euphoria, changes in mood, drowsiness and mental clouding. However, the distinctive feature of the analgesia induced by the opioids is the lack of loss of consciousness. The pain is often described as less intense, but still present although better tolerated. Thus, the opioids do not decrease or treat the cause of the painful stimulus, but rather decrease its perception.

Other effects of opioids include respiratory depression, decreased gastrointestinal motility, sedation, nausea, vomiting, constipation and intestinal bloating. Opioids also have direct cardiovascular effects, decreasing blood pressure, causing vasodilation and decreasing cardiac work.

Opioid medications can be taken in many different ways, including as tablets or pills, injection or patches on the skin.

All opioids are chemically related and work in concert with opioid receptors on nerve cells in the body and central nervous system. Some opioids are stronger than others, but over time you can develop a tolerance to them and may need higher doses to be effective for the same level of pain.

Morphine is considered the prototype opiate, against which other agents are measured for their analgesic effects as well as adverse side effects.

All opioids come in varying strengths or different potencies, based on how strongly they bind to the opioid receptor. The measurement of strength is called ‘oral morphine equivalent daily dose’ (OMEDD). It’s useful to understand the total ‘oral morphine equivalent daily dose’ being taken (for example, fentanyl is 80 to 100 times stronger than morphine). This means that dosages for one narcotic may be significantly different from another. A doctor or pharmacist can help calculate this. Although conversion charts exist (these tell you what dose of a narcotic compares to the equivalent analgesic dose of morphine), these are only at best a guide because other variables, such as an individual’s genetics, also play a part in how a person responds to a narcotic.

How do opioids work?

Opioids attach to proteins called opioid receptors, which are designated µ [mu], κ [kappa] and δ [delta], on nerve cells in your brain and spinal cord (the central nervous system), but are also present on vascular, cardiac, lung, gut and even peripheral blood mononuclear cells. Engagement of the opiate receptors generates a series of intracellular signals, including inhibition of adenylate cyclase, decreased opening of calcium channels, increased potassium currents and activation of protein kinase C (PKC) ⁵. The major effect of these pathways is reduction in cell excitability and neurotransmission. When this happens, the opioids block pain messages sent from the body through the spinal cord to the brain.

The natural ligands for the opiate receptors are the so-called endogenous opioid peptides such as the enkephalins, endorphins and endomorphins.

While opioids can effectively relieve pain, opioids carry some risks and can be highly addictive. The risk of addiction is especially high when opioids are used to manage chronic pain over a long period of time.

What is the difference between acute pain and chronic pain?

Acute pain starts suddenly and is caused by a specific reason. It can stem from a surgery or injury and your body usually heals in a few months. Chronic pain is on-going and the cause of the pain can be less clear or even unknown. This kind of pain comes from a disease, condition, injury or other long-term medical reason. Chronic pain will last for a prolonged period of time.

What opioid medications do?

Opioids are a broad group of pain-relieving drugs that work by interacting with opioid receptors in your cells. Opioids can be made from the poppy plant — for example, morphine (Kadian, Ms Contin, others) — or synthesized in a laboratory — for example, fentanyl (Actiq, Duragesic, others).

When opioid medications travel through your blood and attach to opioid receptors in your brain cells, the cells release signals that muffle your perception of pain and boost your feelings of pleasure.

Are opioids safe?

Prescription opioids are usually safe when used as directed and for short periods of time as directed by your doctor. Due to the risk of abuse, doctors only prescribe opioids when other pain treatments such as non-opioid pain medicines (like acetaminophen or non-steroidal anti-inflammatory drugs [NSAIDs]) do not adequately treat your pain or you cannot take these medications due to side effects, allergies or other problems.

Even when prescribed correctly by a doctor, some people will take opioids for longer than prescribed, use larger quantities, abuse them by taking with alcohol or other drugs, or sell or give them to people illegally. Opioids are frequently misused because they cause euphoria, or a “high” and relaxation, in addition to the pain relief effect.

Is it safe to continue my other medications when taking opioid medications?

Many drugs have the potential to interact negatively with opioid medications. Review all of your medications with your doctor, including over-the-counter (OTC) medications, so you can reduce the risks of interactions with opioids.

Check with your pharmacist before taking over-the-counter (OTC) medication if you’re taking an opioid. Many OTC medications can cause significant drug interactions with opioids. For example, diphenhydramine found in some cold and allergy medications can cause sedative effects and can be dangerous when added to opioid’s sedative side effects.

While many medications can interact with opioid medications, some examples are:

• Alcohol
• Anti-seizure medications, such as carbamazepine (Carbatrol, Tegretol, others), topiramate (Topamax, Qudexy XR, others) and lamotrigine (Lamictal)
• Benzodazepines, such as diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax) and clonazepam (Klonopin)
• Certain antibiotics, including clarithromycin
• Certain antidepressants
• Certain antifungals, including itraconazole (Onmel, Sporanox, Tolsura), voriconazole (Vfend) and ketoconazole
• Certain antiretroviral drugs used for HIV infection, including atazanavir (Reyataz), indinavir (Crixivan) and ritonavir (Norvir)
• Drugs for sleeping problems, such as zolpidem (Ambien, Edluar, others), eszopiclone (Lunesta) and zaleplon (Sonata)
• Drugs used to treat psychiatric disorders, such as haloperidol (Haldol), clozapine (Clozaril, Versacloz), aripiprazole (Abilify) and quetiapine (Seroquel)
• Medications used to treat certain types of nerve pain, such as gabapentin (Neurontin, Gralise) and pregabalin (Lyrica)
• Muscle relaxers, such as cyclobenzaprine (Amrix) and baclofen
• Other opioid medications

Opioid medications affect your brain and may make you sleepy. Mixing these medications with other drugs can heighten these effects, leading to slowed breathing, decreased heart rate and a risk of death.

Signs of a medical emergency include:

• Very small pupils that don’t change size when a light is quickly shined in your eyes
• Losing consciousness or going into a deep sleep from which you can’t be wakened
• Very slow breathing
• Fingernails or lips that appear purple or blue

Call your local emergency number if you or someone you know is experiencing these signs.

Opioid harms

What makes opioid medications effective for treating pain can also make them harmful. Evidence suggests that harmful effects of opioids are more likely to happen to people who take opioids for 3 months or more, or who take higher doses of opioids. The harms from opioids can range from mild to severe and can end up causing death.

Some harms, such as constipation, nausea and drowsiness, tend to occur for a lot of the people who take opioids. Longer term use of opioids increases the risk of bone fractures (breaks), becoming dependent on the opioid and experiencing depression.

Opioids can actually cause more pain. This is called opioid-induced hyperalgesia, and it can occur with long-term use. It happens because taking opioids has made specific nerves and the brain more sensitive to pain.

People taking opioids also need to be careful about mixing them with other medicines that can make them feel sleepy or increase the effects of alcohol. It’s important to tell a doctor about all the medicines being taken.

Does everyone who is prescribed an opioid become addicted?

No, not everyone taking a prescription opioid becomes an addict. When prescription instructions are followed, the chances of becoming addicted are decreased. Opioids are useful for treating acute pain through short-term use. However, when a prescription drug is used outside of the instructions or for chronic pain, the risk of developing an opioid use disorder increases.

Opioid crisis

In the late 1990s, pharmaceutical companies reassured the medical community that patients would not become addicted to prescription opioid pain relievers, and healthcare providers began to prescribe them at greater rates ³. This subsequently led to widespread diversion and misuse of opioid medications before it became clear that these medications could indeed be highly addictive ⁶. Opioid overdose rates began to increase. In 2017, more than 47,000 Americans died as a result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl, a powerful synthetic opioid ⁷. That same year, an estimated 1.7 million people in the United States suffered from substance use disorders related to prescription opioid pain relievers, and 652,000 suffered from a heroin use disorder ⁸. This issue has become a public health crisis with devastating consequences including increases in opioid misuse and related overdoses, as well as the rising incidence of neonatal abstinence syndrome due to opioid use and misuse during pregnancy. The increase in injection drug use has also contributed to the spread of infectious diseases including HIV and hepatitis C.

Opioid crisis key statistics ³:

• Roughly 21 to 29 percent of patients prescribed opioid medications for chronic pain misuse them ⁹
• Between 8 and 12 percent of people using an opioid for chronic pain develop an opioid use disorder ⁹
• An estimated 4 to 6 percent who misuse prescription opioids transition to heroin ¹⁰
• About 80 percent of people who use heroin first misused prescription opioids ¹¹
• Likelihood of developing an opioid use disorder depends on many factors, including length of time a person is prescribed to take opioids for acute pain, and length of time that people continue taking opioids (whether as prescribed, or misused).

Opioid tolerance

You might find that over time you need larger doses of pain medicine. This may be because the pain has increased or you have developed a drug tolerance. Evidence shows that the longer someone takes an opioid, the less pain relief they have. This is because the brain gets used to that opioid dose. This effect is known as tolerance and can lead a person to take higher doses or more types of opioids in order to get the same pain relief.

Drug tolerance occurs when your body gets used to the opioid you’re taking, and it takes more medicine to relieve the pain as well as it once did. Many people do not develop a tolerance to opioids. But if you do develop drug tolerance, usually small increases in the dose or a change in the kind of medicine will help relieve the pain.

Having to increase your dose of opioids to relieve increasing pain or to overcome drug tolerance DOES NOT mean that you are addicted.

Opioid dependence and withdrawal

Dependence is different from tolerance. When someone is dependent on their opioid medication, they will experience withdrawal symptoms if the opioid dose is reduced or stopped. Dependence can occur within one month of starting to take an opioid.

For some people, the main reason they continue to take opioids long-term is to avoid withdrawal symptoms, although they may not realize this. They mistakenly think the opioid is working to reduce pain, when in fact it’s only reducing withdrawal symptoms, which can include pain.

You should not stop taking opioids suddenly. People who need or want to stop taking opioids are usually tapered off the medicine slowly so that their bodies have time to adjust to it. Withdrawal symptoms may occur when people who have been taking narcotic analgesics abruptly stop taking them. Symptoms are like having the flu (flu-like illness) and may include body aches, chills, depression, diarrhea, goose-bumps, headaches, high blood pressure, insomnia, irritability, a runny nose and excessive sweating. Withdrawal symptoms usually last about a week.

Withdrawal symptoms can be treated and tend to go away in a few days or weeks. Again, slowly decreasing your opioid dose over time usually keeps these kinds of symptoms from happening. Check with your doctor about the best way to taper off your pain medicines.

Unless advised otherwise by a doctor, there are also self-management strategies that may help with symptoms experienced by people withdrawing from opioids. General strategies may include:

• relaxation techniques
• listening to music
• using distraction, such as talking to someone with a positive outlook
• drinking plenty of water during withdrawal to replace any fluids lost through sweating and diarrhoea – people on restricted fluids should check with a doctor about fluid intake.

Strategies and medicines for specific symptoms may include:

• nausea and vomiting: eat small, frequent meals, and bland food, avoid spicy, fatty or strong-smelling foods, fructose syrup, ginger (250 mg oral tablets, four times a day) – this is a complementary medicine
• gut cramps: hyoscine butybromide, an over-the-counter (OTC) medicine
• diarrhea: loperamide, an over-the-counter (OTC) medicine
• headaches, muscle aches and pains: paracetamol and/or nonsteroidal anti-inflammatories (NSAIDs) such as ibuprofen oral tablets and gels or creams rubbed into the painful area
• insomnia (inability to sleep): chamomile (3 cups a day)
• anxiety/agitation: lavender oil or another complementary medicine

Opioid use disorder

Opioids can be very addictive and can lead to opioid abuse disorders. Opioid use disorder consists of an overpowering desire to use opioids, increased opioid tolerance, and withdrawal syndrome when discontinued ¹². Opioid use disorder includes dependence and addiction with addiction representing the most severe form of opioid use disorder ¹³. Opioid use disorder is the chronic use of opioids that causes clinically significant distress or impairment ¹². Opioid-use disorder is defined as the repeated occurrence of at least two out of 11 specific opioid-associated problems, including using opioids in increased amounts or for longer than intended; continued use despite interference with daily activities; or still using while in hazardous situations. Severe opioid-use disorder is defined as a cluster of 6 or more problems and it can affect people from all educational and socioeconomic backgrounds.

Opioid use disorders affect over 16 million people worldwide, over 2.1 million in the United States, and there are over 120,000 deaths worldwide annually attributed to opioids ¹⁴.

When an opioid use disorder is being diagnosed, several factors are considered. These factors include:

• Withdrawal when use of the opioid stops
• Use of more and more opioids
• Attempts to cut down or control use are unsuccessful
• Cravings for an opioid
• Continued use of an opioid despite personal, social or work problems

Opioid use disorder diagnosis is based on the American Psychiatric Association DSM-5 ¹⁵ and includes a desire to obtain and take opioids despite social and professional consequences.

Diagnostic Criteria for Opioid Use Disorder DSM-5 ¹⁵:

A. A problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Opioids are often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in failure to fulfill major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
10. Tolerance as defined by either of the following:
    1. A need for markedly increased amounts of opioids to achieve intoxication or desired effect.
    2. A markedly diminished effect with continued use of the same amount of an opioid.
    3. Note: This criterion is not considered to be met for those taking opioids solely under appropriate medical supervision.
11. Withdrawal, as manifested by either of the following:
    1. The characteristic opioid withdrawal syndrome (refer to Criteria A and B of the criteria set for opioid withdrawal).
    2. Opioids (or a closely related substance) are taken to relieve or avoid withdrawal symptoms.
    3. Note: This criterion is not considered to be met for those individuals taking opioids solely under appropriate medical supervision.

Specify if:

• In early remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met for at least 3 months but for less than 12 months (with the exception that Criterion 4A, “Craving, or a strong desire or urge to use opioids,” may be met).
• In sustained remission: After full criteria for opioid use disorder were previously met, none of the criteria for opioid use disorder have been met at any time during a period of 12 months or longer (with the exception that Criterion 4A, “Craving, or a strong desire or urge to use opioids,” may be met).

Specify if:

• On maintenance therapy: This additional specifier is used if the individual is taking a prescribed antagonist medication such as methadone or buprenorphine and none of the criteria for opioid use disorder have been met for that class of medication (except tolerance to or withdrawal from the agonist). This category also applies to those individuals being maintained on a partial agonist, an agonist/antagonist, or a full antagonist such as oral naltrexone or depot naltrexone.

In a controlled environment: This additional specifier is used if the individual is in an environment where access to opioids is restricted.

Specify current severity:

• Mild: Presence of 2–3 symptoms.
• Moderate: Presence of 4–5 symptoms.
• Severe: Presence of 6 or more symptoms.

Opioid abuse disorder treatment

An opioid abuse disorder can be treated through psychological counseling, twelve-step programs and medically-assisted therapies (MAT). Counseling involves shifting the person’s unhealthy behaviors regarding opioid misuse and changing the way they think about opioid use. Medication assisted treatment compliments counseling. Three medications typically come up when discussing medication assisted treatment. Methadone, buprenorphine/naloxone and naltrexone can be used to help lessen symptoms of withdrawal and cravings.

• Methadone: Methadone is an opioid agonist—a drug that fully activates the receptors—works to eliminate symptoms of withdrawal. Methadone reduces cravings by influencing the same opioid receptors in the brain as drugs like heroin, morphine and opioid pain medications. Methadone acts slowly, allowing the patient to feel the effects for a longer stretch of time.
• Buprenorphine: Buprenorphine is a prescription medication that can be used to treat pain and is sometimes used in a combination product with naloxone as part of a medication assisted treatment program for opioid use disorder. Buprenorphine is an opioid agonist, which has high affinity (a strong bond to the cell) for the opioid receptor, but low intrinsic activity (lower ability to make cellular change). It is associated with less opioid-induced hyperalgesia (higher sensitivity to pain) and less respiratory depression (trouble breathing) than other long-acting opioids. This medication produces some feelings of euphoria, but they tend to plateau (level out) as the dose is increased.
• Naltrexone: Naltrexone is an opioid antagonist—a drug that stops opioids by attaching to the receptors and preventing activation. Where Methadone and Buprenorphine still allow some levels of euphoria to be felt by the user, naltrexone does not allow any rewarding euphoria. Because this drug does not produce the rewarding euphoria of other opioids, patients do not always stay on it for a long period of time. However, the FDA approved a long-lasting injectable version of the medication (Vivitrol) that lasts for weeks. This option can help those without easy access to healthcare or those who have trouble regularly taking their medications.

Treatment through medications alone is typically not enough. Behavioral and psychological counseling are usually integrated into the therapy.

Opioid use disorder treatment during pregnancy

The treatment of an opioid use disorder during pregnancy can be difficult. Just as nutrients taken in by the mother influence the growth of a fetus, drug usage can impact the pregnancy. Neonatal abstinence syndrome (NAS) can happen when a pregnant women is abusing opioids while pregnant. As a result, the baby is born with neonatal abstinence syndrome. Some symptoms of neonatal abstinence syndrome include:

• Fetal growth restriction
• Placental abruption
• Preterm labor
• Fetal convulsions
• Fetal death
• Untreated maternal infections like HIV
• Malnutrition

Similarly to medication assisted treatment for opioid use disorders listed above, pregnant women can be treated with medications like methadone, buprenorphine and naltrexone to decrease the dependence of the fetus on opioids. Utilizing these medications can lessen the impact of the opioid on the fetus. Buprenorphine in particular can produce lower instances of neonatal abstinence syndrome by 10 percent, according to the National Institute on Drug Abuse. Use of these medications can stabilize opioid levels in the fetus, improve neonatal results, and are linked to higher weight and gestational age.

Despite using these medications for treatment during pregnancy, neonatal abstinence syndrome can still occur. However, the effects may be decreased when treatment is pursued.

Types of opioids

Opioid medications are divided into two groups:

• Opiates, produced from the opium poppy plant, (including the illegal opioid heroin), and
• Synthetic substances, produced in a laboratory from chemicals.

Opioids can be categorized into subclasses on the basis of their chemical structure as opium alkaloids (opiates: codeine, morphine), semisynthetic derivatives of the natural alkaloids (hydrocodone, hydromorphone, oxycodone, buprenorphine), and various classes of synthetic opioids such as the anililopiperidines (fentanyl, alfentanil, sufentanil, remifentanil), diphenylpropylamine derivatives (propoxyphene, dextropropoxyphene, methadone, diphenoxylate, loperamide), and others (pentazocine, butorphanol, nalbuphine, levorphanol, tramadol), and, the opioid antagonists (nalmefene, naloxone and naltrexone).

Opioids can also be informally classified based upon their major use such as anesthesia (fentanyl, alfentanil, remifentanil, sufentanil), severe pain (morphine, hydromorphone, levorphanol, meperidine), moderate-to-severe acute or chronic pain (transdermal or transbuccal fentanyl, codeine, oxycodone, hydrocodone, levorphanol, methadone), diarrhea (loperamide, diphenoxylate), and cough (codeine, hydrocodone). Finally, opioids can be categorized on the basis of their action as full agonists, partial agonists or mixed agonists/antagonists, and antagonists of opiate receptors.

Commonly used opioid medications contain active ingredients such as buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, tapentadol and tramadol.

Common prescription opioids available in the U.S. include codeine, fentanyl, hydrocodone, morphine, oxycodone, and tramadol.

Some of the most common single agent opioids prescribed for pain in the U.S include:

• Codeine sulfate
• Fentanyl (Actiq, Duragesic, Fentora, Lazanda, Sublimaze, Subsys)
• Hydrocodone (Hysingla ER, Zohydro ER)
• Hydromorphone (Dilaudid)
• Morphine (Kadian, MS Contin)
• Oxycodone (Oxaydo, OxyContin, Roxicodone, Xtampza ER)
• Oxymorphone
• Tramadol (Conzip, Qdolo, Ultram)

If a narcotic analgesic is deemed appropriate, codeine or tramadol should be tried first if the pain is mild-to-moderate. If the pain is unresponsive to these analgesics, or for more severe pain, then hydromorphone, morphine, or oxycodone should be considered. Fentanyl and methadone should only be used for severe pain that is unresponsive to other narcotic analgesics.

Narcotic analgesic combinations contain an opioid with another class of analgesic, such as acetaminophen, ibuprofen or aspirin. They are used to treat moderate to severe pain. Common examples include:

• aspirin, butalbital, caffeine and codeine (Fiorinal with Codeine)
• acetaminophen, butalbital, caffeine and codeine (Fioricet with Codeine)
• acetaminophen and oxycodone (Oxycet, Percocet)
• hydrocodone and ibuprofen
• acetaminophen and hydrocodone (Lortab, Lorcet, Norco, Vicodin)
• acetaminophen, caffeine and dihydrocodeine (Trezix)
• acetaminophen and tramadol (Ultracet)
• naloxone and pentazocine
• aspirin and oxycodone (Percodan)
• acetaminophen and codeine
• acetaminophen, caffeine and dihydrocodeine (Trezix)

Table 1. Common opioids (narcotic analgesics) available in the U.S.

Abbreviations: IM = intramuscular; IV = intravenous; SC = subcutaneous (under the skin); SL = sublingual (under the tongue)

Opioid uses

A doctor may give you a prescription opioid to reduce pain after you have had a major injury or surgery. Doctors and cancer care teams may prescribe opioids for patients having increasing or severe pain from their cancer or their treatment. Opioids are appropriate for the relief of pain due to cancer, or for palliative care or end-of life care. Some doctors also prescribe opioids for chronic non-cancer pain. However, opioids should only be considered to treat chronic non-cancer pain under strict conditions and with close monitoring.

Here are some of the opioids used in cancer care:

• Tramadol (Ultram)
• Hydromorphone (Dilaudid)
• Methadone (Dolophine, Methadose)
• Morphine (Apokyn, Avinza, Kadian, MS-Contin, and others)
• Oxycodone (OxyContin, OxyIR, Roxicodone)
• Hydrocodone
• Oxymorphone (Opana)
• Fentanyl (Actiq, Duragesic, Fentora, Lazanda, Subsys, and others)
• Tapentadol (Nucynta)

An “ER” behind the name of any opioid drug names stands for “extended release,” and is a sign that the drug is taken on a regular schedule to treat chronic pain. An “IR” stands for “immediate release” and means that the drug will work quickly and for only a short time. These rapid-onset opioids are used to treat breakthrough pain. Examples of these types of drugs are fast-acting oral morphine; fentanyl in a lozenge, “sucker,” or under-the-tongue spray. (These forms of fentanyl are absorbed from your mouth – they are not swallowed.)

A short-acting opioid, which relieves breakthrough pain quickly, is often used with a long-acting opioid.

Many times the same opioid drug is used to treat both chronic and breakthrough pain. But, it might be prescribed in 2 different pill forms, one that has only the opioid in it and one that combines an opioid with a non-opioid. Be sure you know what you’re taking because it’s important not to mix them up!

Prescription opioids used for pain relief are generally safe when taken for a short time and as prescribed by your health care provider. However, people who take opioids are at risk for opioid dependence and addiction, as well as an overdose. These risks increase when opioids are misused. Misuse means you are not taking the medicines according to your doctor’s instructions, you are using them to get high, or you are taking someone else’s opioids.

Because opioids can help reduce acute pain and cancer pain, people with chronic non-cancer pain often expect opioids will also reduce or stop the pain they’re feeling. But unfortunately there is no such thing as a ‘pain killer’ and this is especially true for people experiencing chronic non-cancer pain. Opioids can improve pain and the ability to do day-to-day tasks. But this improvement is small and the harms of these medicines also need to be taken into account.

Medical experts recommend that people living with chronic non-cancer pain should first try to manage pain using combinations of treatments and medicines that include:

• gradually increasing physical activity (sometimes called graded activity)
• learning about why and how chronic pain happens
• self-management approaches
• psychological treatments such as cognitive behavioral therapy (CBT)
• the use of certain pain relief medicines such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs).

These treatments are recommended because they can be effective and safe, even more so when done at the same time.

Opioid pain medicines should only be recommended after someone has tried to get the most out of the above treatments but has not felt enough improvement. Even then, it may not be appropriate to take them.

Opioid for chronic non-cancer pain

Opioids have limited value for people with chronic non-cancer pain because the benefits reduce over time, while their potential for harm increases. If a decision to prescribe an opioid for chronic non-cancer pain has been made, then the opioid medicine should first be taken for a trial period. The aim of a trial is to better understand how the person responds to the opioid, as well as work out the lowest dose needed to improve pain and ability to do day-to-day tasks.

What to consider when trialing an opioid:

• How long the trial should go for: This varies for each individual, but up to a maximum of 8 weeks is considered acceptable.
• What dose and what type of opioid to use: ‘Start low, go slow’ with the dose adjusted depending on its effect. Different formulations (eg tablet, capsule, patch) will suit different people.
• What is the goal of treatment: Before starting any medicine it is important to have agreement between the patient and their doctor about the goals of treatment. For people living with chronic non-cancer pain, goals should not just be about pain reduction, but also focus on reducing the impact of pain on day-to-day tasks such as walking the dog, returning to work and attending family activities.
• When to reduce or stop taking opioids: Have an agreement in place in advance on when to start reducing or stopping an opioid. This is known as tapering. The main reason for tapering is that the longer a person takes an opioid, the greater the risk of harms.
• When to come back for a review: People trialling an opioid are encouraged to see their doctor every 1–2 weeks. These visits are used to monitor progress such as activity levels, sleep and social life, and to discuss harms.

Results of a trial

Benefits are weighed against the harms at the end of the trial to help decide whether to continue taking an opioid. If there is no meaningful improvement in symptoms, it is very unlikely that opioid treatment will be helpful. So stopping the opioid is recommended.

If benefits outweigh harms, there can be an agreement between the patient and doctor to continue the trial for another limited time. It’s important to continue regular reviews of harms and benefits.

Opioid side effects

Not everyone has side effects from opioids. The most common side effects are usually sleepiness, constipation, nausea, and vomiting. Some people might also have dizziness, itching, mental effects (such as nightmares, confusion, and hallucinations), slow or shallow breathing, or trouble urinating.

Many side effects from opioid pain medicine can be prevented. Some of the mild ones such as nausea, itching, or drowsiness, often go away without treatment after a few days, as your body adjusts to the medicine. Let your doctor know if you’re having any side effects and ask for help managing them.

At lower doses, opioids may make you feel sleepy, but higher doses can slow your breathing and heart rate, which can lead to death. And the feelings of pleasure that result from taking an opioid can make you want to continue experiencing those feelings, which may lead to addiction.

Here are a few of the more common side effects of opioid use:

• Drowsiness or sleepiness
• Confusion
• Nausea and vomiting
• Constipation
• Respiratory depression (trouble breathing)
• Euphoria
• Itching or a skin rash
• Loss of appetite
• Low blood pressure
• Miosis (constriction of the pupil of the eye)
• Problems with urination
• Shakiness or a tremor
• Slow heartbeat.

You can reduce your risk of dangerous side effects by following your doctor’s instructions carefully and taking your medication exactly as prescribed. Make sure your doctor knows all of the other medications and supplements you’re taking.

Drowsiness or sleepiness

When you first start taking them, opioids might make you sleepy, but this usually goes away after a few days. If your pain has kept you from sleeping, you may sleep more for a few days after starting opioids while you “catch up” on your sleep. You also will get less sleepy as your body gets used to the medicine. Call your doctor or nurse if you still feel too sleepy for your normal activities after you’ve been taking the medicine for a week.

Sometimes it may be unsafe for you to drive a car, or even to walk up and down stairs alone. Don’t do anything that requires you to be alert until you know how the medicine affects you.

Here are some ways to handle sleepiness:

• Wait a few days and see if it goes away.
• Check to see if other medicines you’re taking can also cause sleepiness.
• Ask the doctor if you can take a smaller dose more often or an extended-release opioid.
• Ask your doctor what you can do to get better pain relief, if the opioid is not relieving the pain. The pain itself may be tiring you out. In this case, better pain relief may lead to less sleepiness.
• Ask for a small decrease in the opioid dose. It will still relieve your pain but won’t cause drowsiness. If the drowsiness is very bad, you may be taking more medicine than you need. Talk to your doctor about lowering the amount you’re taking.
• Ask your doctor about changing to a different medicine.
• Ask your doctor if you can take a mild stimulant such as caffeine during the day.
• If drowsiness is bad or if it suddenly starts to be a problem after you’ve been taking opioids for a while, call your doctor or nurse right away.

Constipation

Opioids cause constipation in most people, but it can often be prevented or controlled. Opioids slow the movement of stool through the intestinal tract, which allows more time for water to be absorbed by the body. The stool then becomes hard. When you start taking opioids, it’s best to take a laxative, stool softener, or other treatment to help keep your stool soft and your bowels moving.

Nausea and vomiting

Nausea and vomiting caused by opioids will usually go away after a few days of taking opioid medicine. Some people think they’re allergic if they have nausea after they take an opioid. Nausea and vomiting alone usually are not allergic reactions. But a rash or itching along with nausea and vomiting may be an allergic reaction. If this happens, stop taking the opioid medicine and see your doctor right away. If you have swelling in your throat, hives (itchy welts on the skin), or trouble breathing, get emergency medical help right away.

Opioids overdoses

Opioids also affect the part of your brain that regulates breathing. When people take high doses of opioids, it can lead to an overdose, with the slowing or stopping of breathing and sometimes death.

Anyone who takes an opioid can be at risk of an overdose, but you are at higher risk if you:

• Take illegal opioids
• Take an opioid to get high
• Take an extra dose of a prescription opioid or take it too often (either accidentally or on purpose)
• Combine opioids with other medicines, illegal drugs, and/or alcohol. An overdose can be fatal when mixing an opioid and certain anxiety treatment medicines (benzodiazepines), such as Xanax (alprazolam) or Valium (diazepam).
• Take an opioid medicine that was prescribed for someone else. Children are especially at risk of an accidental overdose if they take medicine not intended for them.
• Have certain medical conditions, such as sleep apnea, or reduced kidney or liver function
• Are over 65 years old

There is also a risk of overdose if you are getting medication-assisted treatment (MAT). Medication-assisted treatment (MAT) is a treatment for opioid abuse and addiction. Many of the medicines used for medication-assisted treatment (MAT) are controlled substances that can be misused.

Signs and symptoms of an opioid overdose

The signs and symptoms of an opioid overdose include:

• The person’s face is extremely pale and/or feels clammy to the touch
• Their body goes limp
• Their fingernails or lips have a purple or blue color
• They start vomiting or making gurgling noises
• They cannot be awakened or are unable to speak
• Their breathing or heartbeat slows or stops
• Coma
• Death

Opioid overdose prevention

There are steps you can take to help prevent an opioid overdose:

• Take your medicine exactly as prescribed by your health care provider. Do not take more medicine at once or take medicine more often than you are supposed to.
• Never mix pain medicines with alcohol, sleeping pills, or illegal substances
• Store medicine safely where children or pets can’t reach it. Consider using a medicine lockbox. Besides keeping children safe, it also prevents someone who lives with you or visits your house from stealing your medicines.
• Dispose of unused medicine promptly

If you take an opioid, it is also important to teach your family and friends how to respond to an opioid overdose. If you are at high risk for an overdose, ask your health care provider about whether you need a prescription for naloxone (commonly known by the brand name Narcan).

Opioids overdoses treatment

An overdose occurs when too much of a substance is taken, harming the body. When too many prescription opioids are taken, breathing can slow and stop. Opioids overdoses can be nonfatal or they can result in death (fatal). Immediate action is needed to help someone experiencing an opioid overdose.

The chance of an overdose increases when opioids are taken in combination with other drugs. Benzodiazepines—sedatives commonly used to treat anxiety or insomnia—act as a depressant to the central nervous system. They greatly increase the risk of overdose death when taken with a prescription opioid.

Opioid receptor antagonists (e.g., naloxone, naltrexone, nalmefene) are used to reverse the effects of opioids and are invaluable in the management of opioid overdose. Specialized opioid antagonists (e.g., naldemedine, naloxegol) can be used to reverse unwanted opioid effects, such as constipation in patients with chronic pain on long-term opioids. These agents (naldemedine, naloxegol) are generally modified so as not to cross the blood brain and reverse the central nervous system effects of opiates.

If you think someone is having an opioid overdose:

• Call local emergency services number immediately
• Naloxone (Narcan) is a drug that treats opioids overdose immediately. Administer naloxone, if it is available. Naloxone is a safe medication that can quickly stop an opioid overdose. Naloxone can reverse the effects of an opioid overdose if it is given to the person quickly. It can be injected into the muscle or sprayed into the nose to rapidly block the effects of the opioid on the body. Medical attention is still needed after Naloxone is administered.
• Try to keep the person awake and breathing
• Lay the person on their side to prevent choking
• Stay with the person until emergency workers arrive.

Alfentanil

Alfentanil is a phenylpiperidine analogue of fentanyl and has a similar spectrum of activity, but differ in its pharmacokinetics, potency and routes of administration. Alfentanil injection (IV) is given together with other medicines to relieve pain during surgery. Alfentanil is also used as a primary anesthesia (numbing medicine) for patients undergoing general surgery. Alfentanil is to be given only by or under the direct supervision of a doctor.

Alfentanil special precautions

• Tell all of your health care providers that you take alfentanil. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until the effects of alfentanil wear off and you feel fully awake.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Alfentanil has an opioid drug in it. Severe side effects have happened when opioid drugs were used with benzodiazepines or other drugs that may make you drowsy or slow your actions. This includes slow or troubled breathing and death. Benzodiazepines include drugs like alprazolam, diazepam, and lorazepam. Benzodiazepines may be used to treat many health problems like anxiety, trouble sleeping, or seizures. If you have questions, talk with your doctor.
• Many drugs interact with alfentanil and can raise the chance of side effects like deadly breathing problems. Talk with your doctor and pharmacist to make sure it is safe to use alfentanil with all of your drugs.
• Do not take with alcohol or products that have alcohol. Unsafe and sometimes deadly effects may happen.
• Alfentanil may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking alfentanil.
• If you are 65 or older, use alfentanil with care. You could have more side effects.
• Alfentanil may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking alfentanil, call your doctor right away.
• Using alfentanil for a long time during pregnancy may lead to withdrawal in the newborn baby. This can be life-threatening. Talk with the doctor.
• Tell your doctor if you are breast-feeding or plan to breast-feed. This medicine passes into breast milk and may harm your baby.

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

• Alcohol abuse, or history of or
• Brain tumor or
• Breathing or lung problems (eg, apnea, COPD, cor pulmonale, respiratory depression, sleep apnea) or
• Drug dependence, especially with narcotics, or history of or
• Head injury, history of—May increase risk for more serious side effects.
• Gallbladder problems or
• Heart disease or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, history of or
• Slow heartbeat—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Alfentanil 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 receiving alfentanil, 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 alfentanil with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using alfentanil 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.

• Acepromazine
• Alefacept
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asciminib
• Asenapine
• Atazanavir
• Avacopan
• Baclofen
• Belzutifan
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Berotralstat
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butalbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desflurane
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Duvelisib
• Efavirenz
• Eletriptan
• Eluxadoline
• Enflurane
• Enzalutamide
• Erdafitinib
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Fexinidazole
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ivosidenib
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lanreotide
• Larotrectinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Lorlatinib
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methoxyflurane
• Methylene Blue
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Octreotide
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pazopanib
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Saquinavir
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Sodium Oxybate
• Sotorasib
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Toloxatone
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Tucatinib
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Voxelotor
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using alfentanil 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.

• Propofol

Alfentanil uses

Alfentanil injection (through a needle placed in one of your veins) is given together with other medicines to relieve pain during surgery. Alfentanil is also used as a primary anesthesia (numbing medicine) for patients undergoing general surgery. A nurse or other trained health professional will give you alfentanil in a hospital.

Alfentanil dosage

Alfentanil will be given on an as needed basis in a healthcare setting.

Adult dose for anesthesia

Uses:

• As an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturates/nitrous oxide/oxygen (generally for surgeries with an expected duration of less than 1 hour).
• As an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia.
• As a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.
• As the analgesic component for monitored anesthesia care (MAC).

Doses should be individualized and titrated to the desired effect according to body weight, physical status, underlying pathological condition, use of other drugs, and type and duration of surgical procedure, and anesthesia.

Spontaneously breathing or assisted ventilation

• Induction of Analgesia: 8 to 20 mcg/kg IV
• Maintenance of Analgesia: 3 to 5 mcg/kg IV every 5 to 20 minutes or 0.5 to 1 mcg/kg/min IV
• Total dose: 8 to 40 mcg/kg

Assisted or controlled ventilation

• Incremental Injection (to attenuate response to laryngoscopy and intubation):
  • Induction of analgesia: 20 to 50 mcg/kg IV
  • Maintenance of analgesia: 5 to 15 mcg/kg IV every 5 to 20 minutes
  • Total dose: Up to 75 mcg/kg
• Continuous Infusion (to provide attenuation of response to intubation and incision):
  • Induction of analgesia: 50 to 75 mcg/kg IV
  • Maintenance of analgesia: 0.5 to 3 mcg/kg/min IV (average rate 1 to 1.5 mcg/kg/min); infusion rates are variable and should be titrated to the desired clinical effect
  • Total dose: Dependent on duration of procedure

Anesthetic induction

• Induction of analgesia: 130 to 245 mcg/kg IV slowly over 3 minutes
• Maintenance of analgesia: 0.5 to 1.5 mcg/kg/min or general anesthetic
• At these doses, truncal rigidity should be expected and a muscle relaxant should be utilized
• Total dose: Dependent on duration of procedure

Monitored Anesthesia Care (MAC)

• Induction of monitored anesthesia care (MAC): 3 to 8 mcg/kg
• Maintenance of monitored anesthesia care (MAC) 3 to 5 mcg/kg every OR 0.25 to 1 mcg/kg/min
• Total dose: 3 to 40 mcg/kg

Continuous infusions

• Infusion Rate: 0.5 to 3 mcg/min
• Infusion rates are variable and should be titrated to the desired clinical effect
• Administer with nitrous oxide/oxygen in patients undergoing general surgery
• See dose adjustments section for dose modifications and discontinuation.

Comments:

• Induction doses should be administered slowly over 3 minutes.
• Fluid replacement should be considered prior to induction as induction doses may produce loss of vascular tone and hypotension.
• Patients receiving monitored anesthesia care (MAC) should be continuously monitored by persons not involved in the surgical or diagnostic procedure.

Adult dose for pain

Uses:

• As an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturates/nitrous oxide/oxygen (generally for surgeries with an expected duration of less than 1 hour).
• As an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia.
• As a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.
• As the analgesic component for monitored anesthesia care (MAC).

Doses should be individualized and titrated to the desired effect according to body weight, physical status, underlying pathological condition, use of other drugs, and type and duration of surgical procedure, and anesthesia:

Spontaneously breathing or assisted ventilation

• Induction of Analgesia: 8 to 20 mcg/kg IV
• Maintenance of Analgesia: 3 to 5 mcg/kg IV every 5 to 20 minutes or 0.5 to 1 mcg/kg/min IV
• Total dose: 8 to 40 mcg/kg

Assisted or controlled ventilation

• Incremental Injection (to attenuate response to laryngoscopy and intubation):
  • Induction of analgesia: 20 to 50 mcg/kg IV
  • Maintenance of analgesia: 5 to 15 mcg/kg IV every 5 to 20 minutes
  • Total dose: Up to 75 mcg/kg
• Continuous Infusion (to provide attenuation of response to intubation and incision):
  • Induction of analgesia: 50 to 75 mcg/kg IV
  • Maintenance of analgesia: 0.5 to 3 mcg/kg/min IV (average rate 1 to 1.5 mcg/kg/min); infusion rates are variable and should be titrated to the desired clinical effect
  • Total dose: Dependent on duration of procedure

Anesthetic induction

• Induction of analgesia: 130 to 245 mcg/kg IV slowly over 3 minutes
• Maintenance of analgesia: 0.5 to 1.5 mcg/kg/min or general anesthetic
• At these doses, truncal rigidity should be expected and a muscle relaxant should be utilized
• Total dose: Dependent on duration of procedure

Monitored Anesthesia Care (MAC)

• Induction of monitored anesthesia care (MAC): 3 to 8 mcg/kg
• Maintenance of monitored anesthesia care (MAC) 3 to 5 mcg/kg every OR 0.25 to 1 mcg/kg/min
• Total dose: 3 to 40 mcg/kg

Continuous infusions

• Infusion Rate: 0.5 to 3 mcg/min
• Infusion rates are variable and should be titrated to the desired clinical effect
• Administer with nitrous oxide/oxygen in patients undergoing general surgery
• See dose adjustments section for dose modifications and discontinuation.

Comments:

• Induction doses should be administered slowly over 3 minutes.
• Fluid replacement should be considered prior to induction as induction doses may produce loss of vascular tone and hypotension.
• Patients receiving monitored anesthesia care (MAC) should be continuously monitored by persons not involved in the surgical or diagnostic procedure.

Pediatric dose for anesthesia

Uses:

• As an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturates/nitrous oxide/oxygen (generally for surgeries with an expected duration of less than 1 hour).
• As an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia.
• As a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.
• As the analgesic component for monitored anesthesia care (MAC).

Doses should be individualized and titrated to the desired effect according to body weight, physical status, underlying pathological condition, use of other drugs, and type and duration of surgical procedure, and anesthesia.

12 years or older

Spontaneously breathing or assisted ventilation

• Induction of Analgesia: 8 to 20 mcg/kg IV
• Maintenance of Analgesia: 3 to 5 mcg/kg IV every 5 to 20 minutes or 0.5 to 1 mcg/kg/min IV
• Total dose: 8 to 40 mcg/kg

Assisted or controlled ventilation

• Incremental Injection (to attenuate response to laryngoscopy and intubation):
  • Induction of analgesia: 20 to 50 mcg/kg IV
  • Maintenance of analgesia: 5 to 15 mcg/kg IV every 5 to 20 minutes
  • Total dose: Up to 75 mcg/kg
• Continuous Infusion (to provide attenuation of response to intubation and incision):
  • Induction of analgesia: 50 to 75 mcg/kg IV
  • Maintenance of analgesia: 0.5 to 3 mcg/kg/min IV (average rate 1 to 1.5 mcg/kg/min); infusion rates are variable and should be titrated to the desired clinical effect
  • Total dose: Dependent on duration of procedure

Anesthetic induction

• Induction of analgesia: 130 to 245 mcg/kg IV slowly over 3 minutes
• Maintenance of analgesia: 0.5 to 1.5 mcg/kg/min or general anesthetic
• At these doses, truncal rigidity should be expected and a muscle relaxant should be utilized
• Total dose: Dependent on duration of procedure

Monitored Anesthesia Care (MAC)

• Induction of monitored anesthesia care (MAC): 3 to 8 mcg/kg
• Maintenance of monitored anesthesia care (MAC) 3 to 5 mcg/kg every OR 0.25 to 1 mcg/kg/min
• Total dose: 3 to 40 mcg/kg

Continuous infusions

• Infusion Rate: 0.5 to 3 mcg/min
• Infusion rates are variable and should be titrated to the desired clinical effect
• Administer with nitrous oxide/oxygen in patients undergoing general surgery
• See dose adjustments section for dose modifications and discontinuation.

Comments:

• Induction doses should be administered slowly over 3 minutes.
• Fluid replacement should be considered prior to induction as induction doses may produce loss of vascular tone and hypotension.
• Patients receiving monitored anesthesia care (MAC) should be continuously monitored by persons not involved in the surgical or diagnostic procedure.

Pediatric dose for pain

Uses:

• As an analgesic adjunct given in incremental doses in the maintenance of anesthesia with barbiturates/nitrous oxide/oxygen (generally for surgeries with an expected duration of less than 1 hour).
• As an analgesic administered by continuous infusion with nitrous oxide/oxygen in the maintenance of general anesthesia.
• As a primary anesthetic agent for the induction of anesthesia in patients undergoing general surgery in which endotracheal intubation and mechanical ventilation are required.
• As the analgesic component for monitored anesthesia care (MAC).

Doses should be individualized and titrated to the desired effect according to body weight, physical status, underlying pathological condition, use of other drugs, and type and duration of surgical procedure, and anesthesia.

12 years or older

Spontaneously breathing or assisted ventilation

• Induction of Analgesia: 8 to 20 mcg/kg IV
• Maintenance of Analgesia: 3 to 5 mcg/kg IV every 5 to 20 minutes or 0.5 to 1 mcg/kg/min IV
• Total dose: 8 to 40 mcg/kg

Assisted or controlled ventilation

• Incremental Injection (to attenuate response to laryngoscopy and intubation):
  • Induction of analgesia: 20 to 50 mcg/kg IV
  • Maintenance of analgesia: 5 to 15 mcg/kg IV every 5 to 20 minutes
  • Total dose: Up to 75 mcg/kg
• Continuous Infusion (to provide attenuation of response to intubation and incision):
  • Induction of analgesia: 50 to 75 mcg/kg IV
  • Maintenance of analgesia: 0.5 to 3 mcg/kg/min IV (average rate 1 to 1.5 mcg/kg/min); infusion rates are variable and should be titrated to the desired clinical effect
  • Total dose: Dependent on duration of procedure

Anesthetic induction

• Induction of analgesia: 130 to 245 mcg/kg IV slowly over 3 minutes
• Maintenance of analgesia: 0.5 to 1.5 mcg/kg/min or general anesthetic
• At these doses, truncal rigidity should be expected and a muscle relaxant should be utilized
• Total dose: Dependent on duration of procedure

Monitored Anesthesia Care (MAC)

• Induction of monitored anesthesia care (MAC): 3 to 8 mcg/kg
• Maintenance of monitored anesthesia care (MAC) 3 to 5 mcg/kg every OR 0.25 to 1 mcg/kg/min
• Total dose: 3 to 40 mcg/kg

Continuous infusions

• Infusion Rate: 0.5 to 3 mcg/min
• Infusion rates are variable and should be titrated to the desired clinical effect
• Administer with nitrous oxide/oxygen in patients undergoing general surgery
• See dose adjustments section for dose modifications and discontinuation.

Comments:

• Induction doses should be administered slowly over 3 minutes.
• Fluid replacement should be considered prior to induction as induction doses may produce loss of vascular tone and hypotension.
• Patients receiving monitored anesthesia care (MAC) should be continuously monitored by persons not involved in the surgical or diagnostic procedure.

Dose adjustments

Obese patients (more than 20% above ideal body weight):

• Concomitant use of other central nervous system (CNS) depressants:
  • Dose reductions of alfentanil may be needed
  • Following administration of alfentanil, the dose of other CNS depressant drugs should be reduced

To reduce incidence of skeletal muscle rigidity:

• Use neuromuscular blocking agent for balance opioid anesthesia; the neuromuscular blocking agent should be appropriate for patient’s cardiovascular status
• For use of alfentanil at doses up to 130 mcg/kg: Administer up to one-fourth of the full paralyzing dose of a neuromuscular blocking agent just prior and following loss of consciousness, give the full paralyzing dose of the neuromuscular blocking agent, or
• Simultaneously give alfentanil with a full paralyzing dose of a neuromuscular blocking agent

Continuous Infusion Dose Adjustments

• Following anesthetic induction dose: Infusion rate should be reduced by 30% to 50% for the first hour of maintenance
• Following anesthetic induction dose: Volatile inhalation anesthetics should be reduced 30% to 50% for the first hour of maintenance.
• For changes in vital signs that indicate a response to surgical stress or lightening of anesthesia: Increase infusion to a maximum of 4 mcg/kg/min and/or give up to 3 IV bolus doses of 7 mcg/kg over 5 minutes
• If still not controlled, a barbiturate, vasodilator, and/or inhalation agent should be used
• Infusion rates should be adjusted downward until there is some response to surgical stimulation
• Within the last 15 minutes of surgery, IV boluses (7 mcg/kg) or a potent inhalation agent should be administered in response to signs of lightening of anesthesia.

Discontinuation

• During general anesthesia, continuous infusions should be discontinued at least 10 to 15 minutes prior to the end of surgery
• For monitored anesthesia care (MAC), infusions may be continued to the end of the procedure

Alfentanil side effects

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.

Alfentanil common side effects:

• drowsiness
• sleepiness

Alfentanil rare side effects:

• False or unusual sense of well-being

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

More common side effects:

• blurred vision
• chest pain or discomfort
• confusion
• difficult or troubled breathing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, slow, pounding, or irregular heartbeat or pulse
• headache
• irregular, fast or slow, or shallow breathing
• lightheadedness, dizziness, or fainting
• nervousness
• not breathing
• pale or blue lips, fingernails, or skin
• pounding in the ears
• sweating
• trouble breathing
• unusual tiredness or weakness

Rare side effects:

• cough
• noisy breathing
• rigid muscles of the neck, arms, and legs
• tightness in the chest

Incidence not known:

• agitation
• cough
• darkening of the skin
• diarrhea
• difficulty with swallowing
• fainting
• fever
• hives, itching, or skin rash
• loss of appetite
• nausea
• overactive reflexes
• poor coordination
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• restlessness
• shivering
• sweating
• talking or acting with excitement you cannot control
• trembling or shaking
• twitching
• vomiting

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

Buprenorphine

Buprenorphine is a strong opioid painkiller. Buprenorphine is used to treat moderate to severe pain, for example during or after an operation or a serious injury, or pain from cancer. Buprenorphine is also used for other types of pain you’ve had for a long time, when weaker painkillers have stopped working. Buprenorphine can also be used to treat drug addiction (either prescription or illegal drugs) and opioid use disorder, but this is usually by a specialist, as part of a complete treatment program that also includes counseling and behavioral therapy.

Buprenorphine is a semisynthetic, highly lipophilic derivative of the opioid alkaloid thebaine ¹⁶. As a partial opioid agonist, buprenorphine maximal effect is less than that of full agonists, which can limit its effectiveness for pain control, and reaches a ceiling where higher doses do not increase the effect ¹⁷. This ceiling makes it much safer than full opioid agonists because respiratory depression is limited. Buprenorphine has high affinity for but low intrinsic activity at the μ (mu) opioid receptors, and will displace morphine, methadone, and other full opioid agonists from those receptors. Full agonists cannot displace buprenorphine; thus, buprenorphine effectively blunts the high of heroin and other full opioid agonists. Buprenorphine’s slow dissociation (disengagement or uncoupling of the drug from the receptor) contributes to its long duration of action ¹⁸. Buprenorphine’s terminal half-life ranges from three hours after intravenous administration to 28 to 37 hours after sublingual administration ¹⁹. The long half-life allows patients to feel stable throughout the day and engage in normal daily activities.

Buprenorphine for pain is available only on prescription. Buprenorphine comes as:

• patches to put on your skin. Buprenorphine patches – release 5 micrograms, 10 micrograms, 15 micrograms or 20 micrograms every hour for 7 days, or 35 micrograms, 52.5 micrograms or 70 micrograms every hour for 3 or 4 days.
• tablets that dissolve in your mouth (sublingual). Buprenorphine tablets – 200 micrograms or 400 micrograms
• injections (usually only given in hospital)
• In 2016, the U.S. Food and Drug Administration (FDA) approved the first extended-release buprenorphine subdermal implant for the treatment of opioid use disorder, with effectiveness comparable to an 8-mg daily dosage of buprenorphine ²⁰. These subdermal implants are indicated for maintenance treatment in patients stabilized on low to moderate dosages of transmucosal buprenorphine (8 mg per day) and are designed to provide steady low levels of buprenorphine for six months, reducing the clinical burden and risk of diversion ²⁰.

Take buprenorphine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of buprenorphine is taken for a long time, it may become habit-forming (causing mental or physical dependence).

To use the buprenorphine buccal film:

• Do not place the medicine on areas of the mouth with sores or lesions.
• Use your tongue to wet the inside of your cheek or rinse your mouth with water before placing the film in your mouth.
• Place the yellow side of the film against the inside of your cheek.
• Press against the film and hold it there with clean, dry fingers for 5 seconds.
• Leave the film in place until it dissolves and do not touch or move it. Do not chew or swallow the film.
• Do not eat or drink anything until the film is completely dissolved, which is usually within 30 minutes.

Do not crush or swallow the sublingual tablet. Place the tablet under the tongue until it is dissolved. If you take 2 or more tablets at a time, place all of the tablets under the tongue together. If this is uncomfortable, place 2 tablets at a time under the tongue and repeat the process until all tablets have been taken. Do not chew or swallow the sublingual tablet.

Use only the brand of buprenorphine that your doctor prescribed. Different brands may not work the same way.

To apply the buprenorphine patch, follow these steps:

1. Clean the area where you plan to apply the patch with clear water and pat completely dry. Do not use any soaps, lotions, alcohols, or oils.
2. Use scissors to cut open the pouch containing the buprenorphine patch along the dotted line. Remove the patch from the pouch and peel off the protective liner from the back of the patch. Try not to touch the sticky side of the patch.
3. Immediately press the sticky side of the patch onto the chosen area of skin with the palm of your hand.
4. Press the patch firmly for at least 15 seconds. Be sure that the patch sticks well to your skin, especially around the edges. Do not rub the patch.
5. If the patch does not stick well or comes loose after it is applied, tape only the edges to your skin with first aid tape. If the patch still does not stick well, you may cover it with Bioclusive or Tegaderm brand see-through dressings. Do not cover the patch with any other type of bandages or tape. Talk to your doctor or pharmacist if your patch continues to have problems sticking to your skin.
6. If a patch falls off before it is time to remove it, dispose of the patch properly and apply a new patch at a different area of skin. Leave the new patch in place for 7 days.
7. When you are finished applying the patch, wash your hands with only clear water right away.
8. Write down the date and time that the patch is applied.
9. When it is time to change your patch, peel off the old patch and apply a new patch to a different skin area.
10. After you remove your patch, use the Patch Disposal Unit provided to you by the manufacturer to safely dispose of the used patch in the trash. Close the Patch Disposal Unit by folding the sticky sides together, then press firmly and smoothly over the entire Unit so that the patch is sealed within. Do not place used patches in the trash without first sealing them in the Patch Disposal Unit. Alternatively, you may also may fold the sticky sides of a used patch together and flush it down the toilet. Used patches may still contain some medication and may be dangerous to children, pets, or adults who have not been prescribed buprenorphine patches.

Buprenorphine special precautions

You should not use buprenorphine if you are allergic to buprenorphine, or:

• if you have used another narcotic drug within the past 4 hours.
• tell your doctor and pharmacist if you are allergic to buprenorphine, any other medications, or any of the ingredients in a buprenorphine patch. Ask your doctor or pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take or use. Be sure to mention the medications listed in the IMPORTANT WARNING and any of the following medications: anticholinergics (atropine, belladonna, benztropine, dicyclomine, diphenhydramine, isopropamide, procyclidine, and scopolamine); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); diuretics (‘water pills’); certain medications for irregular heartbeat including amiodarone (Cordarone, Nexterone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), procainamide (Procanbid), quinidine (in Nuedexta), and sotalol (Betapace, Betapace AF, Sorine, Sotylize, others); lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); certain medications for seizures such as carbamazepine (Tegretol, Teril, others), phenobarbital, phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); trazodone; or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with buprenorphine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have or have ever had conditions mentioned in the IMPORTANT WARNING section or a paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to use buprenorphine patches.
• tell your doctor if you or an immediate family member have or have ever had prolonged QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause loss of consciousness, or sudden death); or if you have or ever had atrial fibrillation; heart failure; seizures; a head injury, a brain tumor, a stroke or any other condition that caused high pressure inside your skull; biliary tract disease; slowed heartbeat; low blood pressure; low blood levels of potassium; problems urinating; or pancreas, thyroid, heart, kidney, or liver disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of using buprenorphine patches.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using a buprenorphine patch.
• you should know that this medication may make you drowsy. Do not drive a car, operate machinery, or do other possibly dangerous activities until you know how this medication affects you.
• you should know that buprenorphine patches may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start using a buprenorphine patch. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that buprenorphine patches may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are using buprenorphine patches.
• you should know that if you have a fever or if you get very hot after physical activity, the amount of buprenorphine that you receive from the patch may increase and possibly cause an overdosage of medication. Avoid physical activity that might cause you to get very hot. Call your doctor right away if you have a fever. Your doctor may need to adjust your dose.

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain problems (eg, tumor, increased intracranial pressure), history of or
• Breathing problems, severe (eg, hypercapnia, hypoxia, sleep apnea) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate (eg, BPH, prostatic hypertrophy) or
• Gallbladder disease or gallstones or
• Head injury, history of or hallucinations, mental illness
• Heart disease (eg, angina, congestive heart failure) or
• Heart rhythm problems (eg, atrial fibrillation, slow heartbeat, long QT syndrome) or
• Hepatitis B or C, history of or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood) or
• Hypothyroidism (an underactive thyroid) or
• Hypovolemia (low blood volume) or
• Kyphoscoliosis (curvature of the spine with breathing problems) or
• Problems with passing urine—Enlarged prostate and urination problems. Use with caution. May increase risk for more serious side effects.
• Kidney disease
• Asthma, acute or severe or
• Respiratory depression (very slow breathing) or
• Stomach or bowel blockage (including paralytic ileus)—Belbuca® should not be used in patients with these conditions.
• Constipation or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas), history of or
• Seizures, history of—Use with caution. May make these conditions worse.
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Mucositis (mouth sores or ulcers)—Use with caution. The effects of the Belbuca® film may be increased because of more drug being absorbed.
• Methadone treatment;

If you use buprenorphine while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks.

Buprenorphine can pass into breast milk and may cause drowsiness, and breathing problems in a nursing baby. There are no adequate studies in women for determining infant risk when using buprenorphine during breastfeeding. Weigh the potential benefits against the potential risks before taking buprenorphine while breastfeeding. Ask your doctor about any risk.

Buprenorphine is not approved for use by anyone younger than 18 years old.

Buprenorphine and pregnancy

Buprenorphine is generally not recommended during pregnancy. There is very little information on taking buprenorphine in pregnancy. If you take buprenorphine at the end of pregnancy there’s a risk that your baby may get withdrawal symptoms or be born addicted to buprenorphine. However, it’s important to treat pain in pregnancy. For some pregnant women with severe pain, buprenorphine might be the best option. Your doctor is the best person to help you decide what’s right for you and your baby.

Buprenorphine and breastfeeding

Buprenorphine is not usually recommended if you’re breastfeeding. Small amounts of buprenorphine pass into breast milk and can cause breathing problems for your baby. Speak to your doctor, as they may want to recommend a different painkiller.

Buprenorphine 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 buprenorphine, 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 buprenorphine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bepridil
• Cisapride
• Dronedarone
• Fluconazole
• Ketoconazole
• Mesoridazine
• Nalmefene
• Naltrexone
• Pimozide
• Piperaquine
• Posaconazole
• Safinamide
• Samidorphan
• Saquinavir
• Sparfloxacin
• Terfenadine

Using buprenorphine 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.

• Acecainide
• Acepromazine
• Alfentanil
• Alfuzosin
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anagrelide
• Apomorphine
• Aprepitant
• Aripiprazole
• Aripiprazole Lauroxil
• Armodafinil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Baclofen
• Bedaquiline
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Bupropion
• Buserelin
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clofazimine
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Dantrolene
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Ebastine
• Efavirenz
• Eletriptan
• Encorafenib
• Enflurane
• Entrectinib
• Enzalutamide
• Eribulin
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Famotidine
• Felbamate
• Fenfluramine
• Fentanyl
• Fexinidazole
• Fingolimod
• Flecainide
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Formoterol
• Fosamprenavir
• Fosaprepitant
• Foscarnet
• Fosphenytoin
• Fospropofol
• Fostemsavir
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halazepam
• Halofantrine
• Haloperidol
• Halothane
• Hexobarbital
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroquinidine
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imatinib
• Imipramine
• Indinavir
• Inotuzumab Ozogamicin
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivabradine
• Ivacaftor
• Ivosidenib
• Ketamine
• Ketazolam
• Ketobemidone
• Lapatinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Lenvatinib
• Leuprolide
• Levocetirizine
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Lumefantrine
• Lurasidone
• Macimorelin
• Magnesium Oxybate
• Meclizine
• Mefloquine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Metronidazole
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Mizolastine
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Moxifloxacin
• Nafarelin
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Nevirapine
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Paliperidone
• Palonosetron
• Panobinostat
• Papaveretum
• Paregoric
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pipamperone
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Ponesimod
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Probucol
• Procainamide
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propafenone
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinidine
• Quinine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Risperidone
• Ritonavir
• Rizatriptan
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Siponimod
• Sodium Oxybate
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John’s Wort
• Sufentanil
• Sulpiride
• Sultopride
• Sumatriptan
• Sunitinib
• Suvorexant
• Tacrolimus
• Tamoxifen
• Tapentadol
• Telaprevir
• Telavancin
• Telithromycin
• Temazepam
• Tetrabenazine
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Thiothixene
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Tolterodine
• Topiramate
• Toremifene
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Triclabendazole
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Triptorelin
• Tryptophan
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Verapamil
• Vilanterol
• Vilazodone
• Vinflunine
• Voclosporin
• Voriconazole
• Vorinostat
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolpidem
• Zopiclone
• Zotepine
• Zuclopenthixol

Other interactions

Using buprenorphine 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 buprenorphine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Buprenorphine uses

Buprenorphine is a strong opioid painkiller. Buprenorphine is used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications, for example during or after an operation or a serious injury, or pain from cancer. Buprenorphine is also used for other types of pain you’ve had for a long time, when weaker painkillers have stopped working.

Buprenorphine can also be used to treat drug addiction (either prescription or illegal drugs) and opioid use disorder, but this is usually by a specialist, as part of a complete treatment program that also includes counseling and behavioral therapy.

Buprenorphine dosage

The dose of buprenorphine 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 buprenorphine. 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 buccal dosage form (film)

• For severe pain:
  • Adults—At first, 75 micrograms (mcg) as a single dose once a day or every 12 hours for at least 4 days. Your doctor may adjust your dose as needed. However, the dose is usually not more than 900 mcg every 12 hours.
  • Children—Use and dose must be determined by your doctor.

For sublingual dosage form (tablets)

• For maintenance treatment of opioid dependence:
  • Adults—4 to 24 milligrams (mg) as a single dose once a day.
  • Children—Use and dose must be determined by your doctor.

Table 2. Buprenorphine formulations for treatment of Opioid Use Disorder

Missed dose

If you miss a dose of buprenorphine, 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.

Buprenorphine side effects

Buprenorphine can cause side effects in some people, but many people have no side effects or only minor ones.

You are more likely to get side effects with higher doses of buprenorphine. Common side effects happen in more than 1 in 100 people. Talk to your doctor or pharmacist if the side effects bother you or do not go away:

• constipation
• feeling or being sick (nausea or vomiting)
• feeling sleepy or tired
• feeling dizzy or a sensation of spinning (vertigo)
• confusion
• headaches
• stomach pain
• itching or skin rashes

Serious side effects

Serious side effects happen in less than 1 in 100 people.

See your doctor (if you are wearing a patch, remove your patch) if:

• your muscles feel stiff for no obvious reason
• you feel dizzy, tired and have low energy – this could be a sign of low blood pressure

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to buprenorphine.

Call your local emergency number or go to emergency department now if:

• you get a skin rash that may include itchy, red, swollen, blistered or peeling skin
• you’re wheezing
• you get tightness in the chest or throat
• you have trouble breathing or talking
• your mouth, face, lips, tongue or throat start swelling

You could be having a serious allergic reaction and may need immediate treatment in hospital.

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

Codeine

Codeine is an opioid pain-relief medication (narcotic analgesic) used for the short-term relief of mild to moderate pain. Codeine is used to treat mild to moderately severe pain and cough. Codeine is not usually recommended for the treatment of chronic (long-term) pain. Codeine belongs to a class of medications called opiate (narcotic) analgesics and to a class of medications called antitussives (cough suppressants). When codeine is used to treat pain, it works by changing the way the brain and nervous system respond to pain. When codeine is used to reduce coughing, it works by decreasing the activity in the part of the brain that causes coughing.

Codeine is only available on prescription from your doctor. If you stop taking codeine suddenly, you may experience withdrawal symptoms.

Codeine is also available in combination with acetaminophen (Capital and Codeine, Tylenol with Codeine), aspirin, carisoprodol, and promethazine and as an ingredient in many cough and cold medications.

Codeine (alone or in combination with other medications) comes as a tablet, a capsule, and a solution (liquid) to take by mouth. It is usually taken every 4 to 6 hours as needed. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take codeine exactly as directed.

If you have taken codeine for several weeks or longer, do not stop taking the medication without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop taking codeine, you may experience withdrawal symptoms such as restlessness, widened pupils (black circles in the center of the eyes), teary eyes, irritability, anxiety, runny nose, difficulty falling asleep or staying asleep, yawning, sweating, fast breathing, fast heartbeat, chills, hair on your arms standing on end, nausea, loss of appetite, vomiting, diarrhea, stomach cramps, muscle aches, or backache.

Shake the solution well before each use to mix the medication evenly. Do not use a household spoon to measure your dose. Use the measuring cup or spoon that came with the medication or use a spoon that is made especially for measuring medication.

Codeine special precautions

You should not use codeine if you have severe breathing problems, a blockage in your stomach or intestines, or frequent asthma attacks or hyperventilation.

You should not use codeine if you are allergic to it, or if you have:

• severe asthma or breathing problems;
• a blockage in your stomach or intestines; or
• frequent asthma attacks or hyperventilation.

In some people, codeine breaks down rapidly in the liver and reaches higher than normal levels in the body. This can cause dangerously slow breathing and may cause death, especially in a child.

Do not give codeine to anyone younger than 18 years old.

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

• Addison’s disease (adrenal gland problem) or
• Alcohol abuse, history of or
• Brain problems (eg, tumor, increased intracranial pressure) or
• Breathing or lung problems (eg, COPD, hypoxia, sleep apnea) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially narcotic abuse or dependence, or history of or
• Enlarged prostate (BPH, prostatic hypertrophy) or
• Head injuries or
• Hypothyroidism (an underactive thyroid) or
• Kyphoscoliosis (curvature of spine that can cause breathing problems) or
• Mental health problems, history of or
• Obesity (overweight) or
• Problems with passing urine or
• Stomach or digestion problems—Use with caution. May increase risk for more serious side effects.
• Breathing problems (eg, asthma, hypercapnia), severe or
• Respiratory depression (hypoventilation or slow breathing) or
• Stomach or bowel blockage (including paralytic ileus)—Should not be used in patients with these conditions.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Some medicines can interact with codeine and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take stimulant medicine, herbal products, or medicine for depression, mental illness, Parkinson’s disease, migraine headaches, serious infections, or prevention of nausea and vomiting. Ask your doctor before making any changes in how or when you take your medications.

If you use codeine while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Tell your doctor if you are pregnant or plan to become pregnant.

Do not breast-feed while taking codeine. This medicine can pass into breast milk and cause drowsiness, breathing problems, or death in a nursing baby.

Before taking codeine:

• tell your doctor and pharmacist if you are allergic to codeine, any other medications, or any of the ingredients in the codeine product you plan to take. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Your doctor will probably tell you not to take codeine if you are taking one or more of these medications, or have taken them within the past 2 weeks.
• 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: bupropion (Aplenzin, Wellbutrin, Zyban); cyclobenzaprine (Amrix); diuretics (‘water pills’); lithium (Lithobid); medications for cough, cold, or allergies; medications for anxiety or seizures; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); 5HT3serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip); trazodone (Oleptro); and tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with codeine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, a blockage or narrowing of your stomach or intestines, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take codeine.
• tell your doctor if you drink or have had recent abdominal or urinary tract surgery. Also tell your doctor if you have or have ever had seizures; mental illness; prostatic hypertrophy (enlargement of a male reproductive gland); urinary problems; low blood pressure; Addison’s disease (condition in which the body does not make enough of certain natural substances); or thyroid, pancreatic, intestinal, gallbladder, liver, or kidney disease.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking codeine.
• tell your doctor if you are breastfeeding. You should not breastfeed while taking codeine. Codeine can cause shallow breathing, difficulty or noisy breathing, confusion, more than usual sleepiness, trouble breastfeeding, or limpness in breastfed infants.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking codeine.
• 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.
• you should know that codeine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking codeine. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that codeine may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

Codeine 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 codeine, 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 codeine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Samidorphan
• Selegiline
• Toloxatone
• Tranylcypromine

Using codeine 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.

• Abametapir
• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asenapine
• Atazanavir
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Cinacalcet
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Enzalutamide
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Fexinidazole
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirabegron
• Mirtazapine
• Mitotane
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenobarbital
• Phenytoin
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinidine
• Quinine
• Ramelteon
• Ranitidine
• Ranolazine
• Remifentanil
• Remimazolam
• Remoxipride
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Rolapitant
• Saquinavir
• Scopolamine
• Secobarbital
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Terbinafine
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using codeine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use codeine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Codeine uses

Codeine is used for the short-term relief of mild to moderate pain. Codeine is also used, usually in combination with other medications, to reduce coughing. Codeine will help relieve symptoms but will not treat the cause of symptoms or speed recovery.

Codeine dosage

The dose of codeine 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 codeine. 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 oral dosage form (tablets)

• For mild to moderate pain:
  • Adults—At first, 15 to 60 milligrams (mg) every 4 hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 360 mg per day.
  • Children 12 to 18 years of age—Use and dose must be determined by your doctor.
  • Children younger than 12 years of age—Should not be used in these patients.

Missed dose

Codeine is usually taken as needed. If your doctor has told you to take codeine 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.

Codeine side effects

All opioids, including codeine, can have side effects including life-threatening breathing problems. The risk of these is higher:

• when first taking codeine
• after a dosage increase
• if you are older
• if you have an existing lung problem

The side effects of codeine are similar to those of other opioids, and include:

• constipation
• nausea and stomach cramps
• mood changes
• dizziness
• drowsiness
• feeling faint
• inability to sleep and unusual dreams

Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• stomach pain
• difficulty urinating

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNINGS section, stop taking codeine and call your doctor immediately or get emergency medical attention:

• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• noisy or shallow breathing
• difficulty breathing or swallowing
• changes in heartbeat
• rash
• itching
• hives
• changes in vision
• seizures

Codeine may cause other side effects. Call your doctor if you have any unusual problems while you are taking codeine.

Fentanyl

Fentanyl is a fully synthetic opioid that is more potent that morphine and is commonly used for management of severe pain and as an adjunct to general anesthesia.

Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications.

Fentanyl special precautions

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

• Adrenal problems or
• Brain tumor, history of or
• Breathing or lung problems (eg, COPD, respiratory depression, sleep apnea) or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially with narcotics, or history of or
• Head injury, history of or
• Heart disease or
• Hypokalemia (low potassium levels in the blood) or
• Hypomagnesemia (low magnesium levels in the blood)—Use with caution. May increase risk for more serious side effects.
• Bradycardia (slow heart rhythm) or
• Gallbladder problems or
• Heart rhythm problems (eg, QT prolongation) or
• Hypertension (high blood pressure) or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation or swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Before using fentanyl:

• tell your doctor and pharmacist if you are allergic to fentanyl patches, injection, nasal spray, tablets, lozenges, or films; any other medications; or any of the ingredients in fentanyl tablets, lozenges, or films. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following medications: antihistamines; barbiturates such as phenobarbital; buprenorphine (Buprenex, Subutex, in Suboxone); butorphanol (Stadol); carbamazepine (Carbatrol, Epitol, Tegretol); efavirenz (Sustiva, in Atripla); modafinil (Provigil); nalbuphine (Nubain); naloxone (Evzio, Narcan); nevirapine (Viramune); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); oxcarbazepine (Trileptal); pentazocine (Talwin); phenytoin (Dilantin, Phenytek); pioglitazone (Actos, in Actoplus Met, in Duetact); rifabutin (Mycobutin); and rifampin (Rifadin, Rimactane, in Rifamate, in Rifater). Also tell your doctor or pharmacist if you are taking any of the following medications or if you have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol or uses or has ever used street drugs or excessive amounts of prescription medications. Also tell your doctor if you have or have ever had a head injury, a brain tumor, a stroke, or any other condition that caused high pressure inside your skull; seizures; slowed heartbeat or other heart problems; low blood pressure; mental problems such as depression, schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions), or hallucinations (seeing things or hearing voices that do not exist); breathing problems such as asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic bronchitis and emphysema); or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using fentanyl, call your doctor.
• you should know that fentanyl may decrease fertility in men and women. Talk to your doctor about the risks of using fentanyl.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using fentanyl.
• you should know that fentanyl may make you drowsy or dizzy. Do not drive a car or operate machinery until you know how this medication affects you.
  you should know that fentanyl may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start using fentanyl. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• if you have diabetes, you should know that each fentanyl lozenge (Actiq) contains about 2 grams of sugar.
• if you will be using the lozenges (Actiq), talk to your dentist about the best way to care for your teeth during your treatment. The lozenges contain sugar and may cause tooth decay and other dental problems.
• you should know that fentanyl may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

Check with your doctor at regular times while using fentanyl. Be sure to report any side effects. It is very important that your doctor check your or your child’s progress while using fentanyl. This will allow your doctor to see if fentanyl is working properly and to decide if you should continue to take it. Blood and urine tests may needed to check for unwanted effects.

Do not touch the sticky side of the patch or the gel. Fentanyl can be quickly absorbed through your eyes and mouth and can be extremely dangerous. If you do touch the sticky side of the fentanyl patch or gel, let your nurse or doctor know right away and rinse the area with large amounts of water. Do not use soaps or other cleansers.

After you have been using fentanyl for awhile, “breakthrough” pain may occur more often than usual, and it may not be relieved by your regular dose of fentanyl. If this occurs, do not increase the amount of fentanyl skin patch or other narcotic that you are using without first checking with your doctor.

Fentanyl will add to the effects of alcohol and other central nervous system (brain and spinal cord) depressants. Central nervous system depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of central nervous system depressants are antihistamines or medicine for hay fever, other allergies, or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, benzodiazepines, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. This effect may last for a few days after you stop using this medicine. Check with your doctor before taking any of the medicines listed while you are using this medicine.

The Ionsys® patch must be removed before a procedure called a magnetic resonance imaging (MRI) scan. It may cause skin burns if left in place during the procedure.

The Ionsys® patch may cause serious skin reactions. Call you doctor right away if you have blistering, lesions, a rash, redness, or swelling of the skin, especially at the site of application.

Fentanyl may cause some people to become drowsy, dizzy, or lightheaded, or to feel a false sense of well-being. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. These effects usually go away after a few days of treatment, when your body gets used to the medicine. However, check with your doctor if drowsiness that is severe enough to interfere with your activities continues for more than a few days.

Dizziness, lightheadedness, or even fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve dizziness or lightheadedness.

Nausea or vomiting may occur, especially during the first several days of treatment. Lying down for a while may relieve these effects. However, if they are especially bothersome or if they continue for more than a few days, check with your doctor. You may be able to take another medicine to help prevent these problems.

Using narcotics for a long time may cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

Heat can cause the fentanyl in the patch to be absorbed into your body faster. This may increase the chance of serious side effects or an overdose. While you are using this medicine, do not use a heating pad, electric blanket, heat or tanning lamps, sauna, a sunlamp, or a heated water bed, and do not sunbathe, or take long baths or showers in hot water. Also, check with your doctor if you get a fever.

Be careful about letting other people come in contact with your patch. The patch could stick to someone else, such as when you hug them or if someone helps you put the patch on. If any medicine gets on another person, wash it off right away with clear water.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are using fentanyl. Serious side effects can occur if your medical doctor or dentist gives you certain other medicines without knowing that you are using fentanyl.

You may bathe, shower, or swim while wearing a fentanyl skin patch. However, be careful to wash and dry the area around the patch gently. Rubbing may cause the patch to get loose or come off. If this does occur, throw away the patch and apply a new one in a different place. Make sure the area is completely dry before applying the new patch.

If you have been using fentanyl regularly for several weeks or more, do not suddenly stop using it without first checking with your doctor. You may be directed to gradually reduce the amount you are using before stopping treatment completely to lessen the chance of withdrawal side effects.

Using too much fentanyl skin patch, or taking too much of another narcotic with fentanyl skin patch, may cause an overdose. If this occurs, get emergency help right away. An overdose can cause severe breathing problems (breathing may even stop), unconsciousness, and death. Serious signs of an overdose include: very slow breathing (fewer than 8 breaths a minute) and drowsiness that is so severe that you are not able to answer when spoken to, or, if asleep, cannot be awakened. Other signs of an overdose may include: cold, clammy skin, low blood pressure, pinpoint pupils of the eyes, and slow heartbeat. It may be best to have a family member or a friend check on you several times a day when you start using a narcotic regularly, and whenever your dose is increased, so that he or she can get help for you if you cannot do so yourself.

Fentanyl may cause sleep-related breathing problems (e.g., sleep apnea, sleep-related hypoxemia). Your doctor may decrease your dose if you have sleep apnea (stop breathing for short periods during sleep) while using this medicine.

Do not use a fentanyl patch if you have taken a monoamine oxidase (MAO) inhibitor in the past 2 weeks. Some examples of MAO inhibitors are isocarboxazid (Marplan®), phenelzine (Nardil®), selegiline (Eldepryl®), and tranylcypromine (Parnate®). If you use the 2 medicines close together it may cause serious side effects like confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high temperature, an extremely high blood pressure, or severe convulsions.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Using fentanyl while you are pregnant may cause serious unwanted effects, including neonatal opioid withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using fentanyl.

Using too much of fentanyl may cause reduced infertility (unable to have children). Talk with your doctor before using fentanyl if you plan to have children.

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.

Fentanyl and pregnancy

Very little is known about how fentanyl might affect a baby’s development in the womb and it is therefore not possible to say that it is safe. Fentanyl is generally not recommended during pregnancy. In early pregnancy, it’s been linked to some problems for your baby. If you take fentanyl at the end of pregnancy there’s a risk that your baby may get withdrawal symptoms or be born addicted to fentanyl. However, it’s important to treat severe pain in pregnancy. For some pregnant women with severe pain, fentanyl might be the best option. Any assessment of safety needs to weigh up the risks and benefits to both mother and baby of using fentanyl against those of not using fentanyl. The outcome of this assessment will vary from person to person and will depend on the severity of the mother’s condition. Your doctor is the best person to help you decide what’s right for you and your baby.

When deciding whether to use fentanyl during pregnancy it is therefore important to weigh up how necessary it is to your health against any possible risks to you or your baby, some of which might depend on how many weeks pregnant you are.

Recreational use of fentanyl in pregnancy is not advised as there is no benefit to the health of the mother or baby in this context. Recreational fentanyl use also carries a high risk of overdose and death. If you are pregnant and use fentanyl recreationally it is important that your doctor or midwife is aware of this. If necessary, they will be able to get you help and support to safely stop using fentanyl.

Can using fentanyl in early pregnancy cause my baby to be born with birth defects?

A baby’s body and most internal organs are formed during the first 12 weeks of pregnancy. It is mainly during this time that some medicines are known to cause birth defects.

There are currently no large scientific studies that have investigated whether fentanyl use during the first trimester of pregnancy can cause birth defects in the baby. Experts have been able to identify case studies of only four babies who were born to pregnant women who used fentanyl in the first trimester. None of these babies had birth defects, however information on many more pregnancies needs to be collected before it is possible to accurately assess whether fentanyl causes birth defects.

Can taking fentanyl in pregnancy cause miscarriage, stillbirth, preterm birth, or my baby to be small at birth (low birth weight)?

No studies have specifically analysed whether these outcomes are more or less common in pregnant women taking fentanyl.

Can using fentanyl in pregnancy cause other health problems in the baby/child?

Withdrawal symptoms at birth

Withdrawal symptoms are thought to occur as the newborn baby’s body has to adapt to no longer getting certain types of medicines through the placenta. Medicines related to fentanyl are known to increase the risk of withdrawal symptoms in the baby when used around the time of delivery.

There are a small number of reports in the scientific literature of babies who had withdrawal symptoms after being exposed to fentanyl in the womb. If you have used fentanyl regularly in pregnancy it is important to let your doctor or midwife know as it might be advisable that your baby is born in a unit with facilities to monitor and treat withdrawal symptoms if necessary.

Learning and behavioural problems in the child

A baby’s brain continues to develop right up until the end of pregnancy. It is therefore possible that taking certain medicines at any stage of pregnancy could have a lasting effect on a child’s learning or behavior.

There are no studies that have been specifically designed to investigate whether fentanyl exposure in the womb might affect a child’s learning and behaviour. Nearly all medicines still need to be studied to determine whether exposure in the womb might affect a child’s learning or behaviour.

Will I or my baby need extra monitoring during pregnancy?

Most women will be offered a scan at around 20 weeks of pregnancy to look for birth defects as part of their routine antenatal care.

Because the effects of taking fentanyl in early pregnancy are largely unknown, your doctor may suggest extra monitoring of your baby, including more detailed or earlier scans to detect birth defects, and more frequent reviews of your baby’s growth in the womb.

Women with some of the underlying conditions that fentanyl can be used to treat might be more closely monitored to ensure that their baby is growing and moving as expected. Women who use fentanyl recreationally might also receive extra monitoring.

Fentanyl and breastfeeding

Fentanyl is not usually recommended if you’re breastfeeding. Small amounts of fentanyl pass into breast milk and can cause breathing problems for your baby. Speak to your doctor as they may want to recommend a different painkiller.

The results of studies on the effect of epidural fentanyl on breastfeeding initiation and duration are mixed and controversial, because of the many different combinations of drugs, dosages and patient populations studied as well as the variety of techniques used and deficient designs of many of the studies. It has been suggested that a cumulative dose of over 150 mcg of fentanyl during labor and delivery reduces breastfeeding success ²¹, but another study found no marked decrease in breastfeeding success with doses above 150 mcg in motivated women with previous breastfeeding success ²². In infants placed skin-to-skin after a normal vaginal delivery, epidural fentanyl given during labor may delay the infant’s first suckling in a dose-dependent manner ²³, perhaps because it can persist in the infant’s serum for over 24 hours after discontinuation ²⁴. However, it appears that with good breastfeeding support, epidural fentanyl plus bupivacaine has little overall effect on breastfeeding success ²⁵.

No waiting period or discarding of milk is required before resuming breastfeeding after fentanyl is used for short procedures (e.g., for endoscopy) ²⁶. After general anesthesia, breastfeeding can be resumed as soon as the mother has recovered sufficiently from anesthesia to nurse. When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure. Limited information indicates that transdermal fentanyl in a dosage of 100 mcg/hour results in undetectable fentanyl concentrations in breastmilk.

Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother’s milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of fentanyl to a few days at a low dosage with close infant monitoring ²⁷. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

What special dietary instructions should I follow?

Do not eat grapefruit or drink grapefruit juice while using fentanyl.

Grapefruit juice can increase the amount of fentanyl in your body so it’s a good idea not to drink more than a large glass of it.

It’s best not to drink alcohol when you first start taking or using fentanyl until you see how it affects you.

Fentanyl is not generally affected by food so you can eat normally.

Can I drink alcohol with fentanyl?

It’s best not to drink alcohol when you first start taking or using fentanyl until you see how it affects you.

Drinking alcohol while taking fentanyl will make you more sleepy and increases the risk of serious side effects.

Fentanyl 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 receiving fentanyl, 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 fentanyl with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Mifepristone
• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using fentanyl 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.

• Abametapir
• Acepromazine
• Alefacept
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asciminib
• Asenapine
• Atazanavir
• Avacopan
• Baclofen
• Belzutifan
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Berotralstat
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Eluxadoline
• Enflurane
• Enzalutamide
• Erdafitinib
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fexinidazole
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketobemidone
• Ketoconazole
• Lanreotide
• Lasmiditan
• Lefamulin
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Lorlatinib
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Mibefradil
• Midazolam
• Milnacipran
• Mirtazapine
• Mitotane
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicardipine
• Nicomorphine
• Nifedipine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Octreotide
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pazopanib
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Saquinavir
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• Sotorasib
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tacrolimus
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Tucatinib
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Voxelotor
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using fentanyl 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 fentanyl, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Fentanyl uses

Fentanyl has a rapid onset and short duration of action, making it particularly effective in anesthesia induction as well as maintenance ²⁸. Fentanyl was approved for use in general anesthesia in the United States in 1968 and is still widely used in anesthesia practice ²⁸. With the development of transdermal and buccal formulations of fentanyl, it was approved for use in pain management and has become the most widely used synthetic opioid in clinical practice.

Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur despite round the clock treatment with pain medication) in cancer patients at least 18 years of age (or at least 16 years of age if using Actiq brand lozenges) who are taking regularly scheduled doses of another narcotic (opiate) pain medication, and who are tolerant (used to the effects of the medication) to narcotic pain medications. Tolerance occurs when you need a higher and/or more frequent amount of a drug to get the desired effects. Fentanyl should not be prescribed for other uses; ask your doctor or pharmacist for more information.

Fentanyl dosage

The different types of fentanyl come in a range of strengths:

• Fentanyl patches – these release 12 micrograms to 100 micrograms of fentanyl every hour
• Fentanyl nasal spray – 50 micrograms to 400 micrograms
• Fentanyl tablets – 100 micrograms to 800 micrograms
• Fentanyl lozenges – 200 micrograms to 1,600 micrograms

The dose of fentanyl 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 fentanyl. If your dose is different, do not change it unless your doctor tells you to do so.

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

Discontinue all other extended-release opioids when beginning therapy.

Due to the risk of respiratory depression, the transdermal patch is for use in opioid-tolerant patients only; opioid tolerant patients have been taking at least: morphine 60 mg daily, oral oxycodone 30 mg daily, oral hydromorphone 8 mg daily, or an equianalgesic dose of another opioid for 1 week or longer.

Dose for chronic pain

For transdermal dosage form (Duragesic® skin patch):

• For relief of chronic pain:
  • Adults and children 2 years of age and older: Your doctor will decide which dose of the patch you need based on your present daily narcotic dose. The patch is applied to the skin and left in place for 3 days (72 hours). Your doctor may adjust your dose as needed.
  • Children younger than 2 years of age: Use and dose must be determined by your doctor.

For transdermal dosage form (Ionsys® skin patch) (the Ionsys® patch is not for use at home):

• For short-term relief of acute pain after surgery:
  • Adults—Your doctor will decide which dose of the patch you need based on your present daily narcotic dose. The patch is applied by your healthcare provider to your upper outer arm or chest. Your doctor will show you how to adjust your dose as needed while in the hospital.

Adult dose for breakthrough pain

For the management of breakthrough pain in patients who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.

Transmucosal products

• For use in patients who are opioid-tolerant and taking around-the-clock opioids. Opioid tolerant patients have been taking at least: morphine 60 mg daily, oral oxycodone 30 mg daily, oral hydromorphone 8 mg daily, or an equianalgesic dose of another opioid for 1 week or longer.
• All transmucosal products must be individually titrated to an effective and tolerable dose. Once titrated, these products are used to treat up to 4 episodes of breakthrough pain a day; if a patient is experiencing more than 4 breakthrough episodes per day, the around-the-clock opioid dose should be re-evaluated. If the around-the-clock opioid dose is adjusted, re-adjustment of the transmucosal product may be necessary.
• Transmucosal fentanyl products are not bioequivalent; patients should not be interchanged on a mcg per mcg basis from 1 fentanyl product to any other fentanyl product

Transmucosal lozenge (Actiq)

The lozenge should be placed in mouth between cheek and lower gum and sucked; occasionally move from side to side using the handle; do not chew. If signs of excessive opioid effects appear before the lozenge is consumed, the lozenge should be removed immediately and subsequent doses should be decreased.

• Initial dose: 200 mcg consumed over 15 minutes
• Dose titration: If breakthrough pain is not relieved 15 minutes after completion of 1 unit (30 minutes after start), 1 additional unit of the same strength may be taken; Patients must wait at least 4 hours before re-treating. If breakthrough pain had not been relieved with 1 unit, the dose should be increased to the next highest strength with subsequent episodes of pain.
• Maintenance dose: An effective dose is achieved when 1 unit is mostly sufficient to treat an episode of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given 15 minutes after completion (30 minutes after start); no more than 2 doses should be used to treat any episode of breakthrough pain.
• Maximum dose: 4 breakthrough episodes per day at intervals of at least 4 hours

Nasal spray (Lazanda)

• Initial dose: 100 mcg sprayed in 1 nostril
• Dose titration: If adequate analgesia is not achieved after 30 minutes, the dose should be escalated in a step-wise manner over consecutive episodes. Patients must wait at least 2 hours between doses. Patients should confirm the dose that works for them with a second episode of breakthrough pain.
• Maintenance dose: Once an effective dose has been established, patients should use that dose for each subsequent breakthrough episode.
• Maximum dose: 800 mcg per dose; 4 breakthrough episodes per day at intervals of at least 2 hours

Sublingual tablet (Abstral)

The sublingual tablet should be placed on the floor of the mouth and allowed to completely dissolve; do not eat or drink until the tablet is completely dissolved. The initial dose of the sublingual tablet is always 100 mcg except in patients receiving the transmucosal lozenge – see dose adjustment section for initial dosing recommendations for these patients.

• Initial dose: 100 mcg sublingually
• Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be taken. Patients must wait at least 2 hours before re-treating. Dose escalation should proceed in a stepwise manner (200 to 300 to 400 to 600 to 800 mcg) as needed. During titration, multiples of 100 mcg and/or 200 mcg tablets may be used for any single dose. Patients should not use more than 4 tablets at one time.
• Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
• Maximum dose: 4 episodes per day; 800 mcg per dose at intervals of at least 2 hours

Sublingual spray

Spray into mouth underneath the tongue. The initial dose of is always 100 mcg except in patients receiving the transmucosal lozenge – see dose adjustment section for initial dosing recommendations for these patients.

• Initial dose: 100 mcg sprayed sublingually
• Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be used. Patients must wait at least 4 hours before re-treating. If breakthrough pain is not relieved with the 100 mcg dose, dose escalation should proceed in a stepwise manner (200 to 400 to 600 to 800 to 1200 to 1600 mcg) for subsequent episodes of pain.
• Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
• Maximum dose: 4 episodes per day at intervals of at least 4 hours

Buccal tablet (Fentora)

Tablet should be placed in the buccal cavity (above the rear molar, between the upper cheek and gum); alternatively, may be placed under the tongue. The initial dose of is always 100 mcg except in patients receiving the transmucosal lozenge – see dose adjustment section for initial dosing recommendations for these patients.

• Initial dose: 100 mcg buccally
• Dose titration: If adequate analgesia is not obtained after 30 minutes, a second dose of the same strength may be taken. Patients must wait at least 4 hours before re-treating. If breakthrough pain is not relieved with 100 mcg, the next dose should be two 100 mcg tablets (one on each side of the mouth in the buccal cavity). The patient may be further titrated in a stepwise manner. During titration, multiples of 100 mcg or 200 mcg tablets may be used for any single dose. Patients should not use more than 4 tablets at one time.
• Maintenance dose: An effective dose is achieved when 1 dose is sufficient to treat most episodes of breakthrough pain; however, if there is inadequate analgesia a second dose of the same strength may be given after 30 minutes; no more than 2 doses should be used to treat any episode of breakthrough pain. Patients should limit treatment to 4 or fewer breakthrough episodes per day.
• Maximum dose: 4 episodes per day; at intervals of at least 4 hours

Adult dose for anesthesia

Premedication for anesthesia:

• 50 to 100 mcg IM, 30 to 60 minutes prior to surgery.
• Lozenge: 5 mcg/kg (400 mcg is the maximum dose).
• Lower doses should be used for vulnerable patients.

General Anesthesia:

• Total Low dose: 2 mcg/kg (minor procedures).
• Maintenance low dose: Infrequently needed.
• Total Moderate dose: 2 to 20 mcg/kg.
• Maintenance moderate dose: 25 to 100 mcg IV/IM.
• Total high dose: 20 to 50 mcg/kg (prolonged surgeries).
• Maintenance high dose: 25 mcg to half of the initial dose.

Adjunct to regional anesthesia:

• 50 to 100 mcg IM or slow IV over 3 to 5 minutes as required.

Postoperative:

• 50 to 100 mcg IM. May repeat dose in 1 to 2 hours as needed.

Pediatric dose for anesthesia

Doses should be titrated to appropriate effects; a wide range of doses is possible depending upon desired degree of analgesia/anesthesia, clinical environment, patient’s status, and presence of opioid tolerance.

Neonates analgesia (International Evidence-Based Group for Neonatal Pain recommendations):

• Intermittent doses: Slow IV push: 0.5 to 3 mcg/kg/dose
• Continuous IV infusion: 0.5 to 2 mcg/kg/hour
• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Mean required dose: Neonates with gestational age less than 34 weeks: 0.64 mcg/kg/hour; neonates with gestational age greater than or equal to 34 weeks: 0.75 mcg/kg/hour
• Continuous sedation/analgesia during extracorporeal membrane oxygenation (ECMO): Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Younger infants:

• Sedation/analgesia: Slow IV push: 1 to 4 mcg/kg/dose; may repeat every 2 to 4 hours
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg, then 0.5 to 1 mcg/kg/hour; titrate upward
• Continuous sedation/analgesia during extracorporeal membrane oxygenation ECMO: Initial IV bolus: 5 to 10 mcg/kg slow IV push over 10 minutes, then 1 to 5 mcg/kg/hour; titrate upward; tolerance may develop; higher doses (up to 20 mcg/kg/hour) may be needed by day 6 of ECMO.

Older Infants and Children 1 to 12 years:

• Sedation for minor procedures/analgesia: IM or IV: 1 to 2 mcg/kg/dose; may repeat at 30 to 60 minute intervals. Note: Children 18 to 36 months of age may require 2 to 3 mcg/kg/dose.
• Intranasal: Children greater than or equal to 10 kg: 1.5 mcg/kg once (maximum: 100 mcg/dose); reported range: 1 to 2 mcg/kg; some studies allowed for additional incremental doses of 0.5 mcg/kg to be administered every 5 minutes, not to exceed a total dose of 3 mcg/kg depending on pain type and severity.
• Continuous sedation/analgesia: Initial IV bolus: 1 to 2 mcg/kg then 1 mcg/kg/hour; titrate upward; usual: 1 to 3 mcg/kg/hour; some require 5 mcg/kg/hour

Children greater than or equal to 5 years and less than 50 kg:

• Patient-controlled analgesia (PCA): IV: Opioid-naive: Note: patient-controlled analgesia has been used in children as young as 5 years of age; however, clinicians need to assess children 5 to 8 years of age to determine if they are able to use the patient-controlled analgesia device correctly. All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting patient-controlled analgesia for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed.

Usual concentration: Determined by weight; some clinicians use the following:

• Children less than 12 kg: 10 mcg/mL
• Children 12 to 30 kg: 25 mcg/mL
• Children greater than 30 kg: 50 mcg/mL
• Demand dose: Usual initial: 0.5 to 1 mcg/kg/dose; usual range: 0.5 to 1 mcg/kg/dose
• Lockout: Usual initial: 5 doses/hour
• Lockout interval: Range: 6 to 8 minutes
• Usual basal rate: 0 to 0.5 mcg/kg/hour

Children greater than 12 years to adult:

• Sedation for minor procedures/analgesia: IV: 0.5 to 1 mcg/kg/dose; may repeat after 30 to 60 minutes; or 25 to 50 mcg, repeat full dose in 5 minutes if needed, may repeat 4 to 5 times with 25 mcg at 5 minute intervals if needed. Note: Higher doses are used for major procedures.
• Continuous sedation/analgesia:
  • Less than 50 kg: Initial IV bolus: 1 to 2 mcg/kg; continuous infusion rate: 1 to 2 mcg/kg/hour
  • Greater than 50 kg: Initial IV bolus: 1 to 2 mcg/kg or 25 to 100 mcg/dose; continuous infusion rate: 1 to 2 mcg/kg/hour or 25 to 200 mcg/hour
• Patient-controlled analgesia (PCA): IV: Children greater than 50 kg, Adolescents greater than 50 kg, and Adults: Note: All patients should receive an initial loading dose of an analgesic (to attain adequate control of pain) before starting patient-controlled analgesia for maintenance. Adjust doses, lockouts, and limits based on required loading dose, age, state of health, and presence of opioid tolerance. Use lower end of dosing range for opioid-naive. Assess patient and pain control at regular intervals and adjust settings if needed:
  • Usual concentration: 50 mcg/mL
  • Demand dose: Usual initial: 20 mcg; usual range: 10 to 50 mcg
  • Lockout interval: Usual initial: 6 minutes; usual range: 5 to 8 minutes
  • Usual basal rate: less than or equal to 50 mcg/hour

Preoperative sedation, adjunct to regional anesthesia, postoperative pain: IM, IV: 25 to 100 mcg/dose

Adjunct to general anesthesia: Slow IV:

• Low dose: 0.5 to 2 mcg/kg/dose depending on the indication
• Moderate dose: Initial: 2 to 20 mcg/kg/dose; Maintenance (bolus or infusion): 1 to 2 mcg/kg/hour. Discontinuing fentanyl infusion 30 to 60 minutes prior to the end of surgery will usually allow adequate ventilation upon emergence from anesthesia. For “fast-tracking” and early extubation following major surgery, total fentanyl doses are limited to 10 to 15 mcg/kg.
• High dose: 20 to 50 mcg/kg/dose; Note: High dose fentanyl as an adjunct to general anesthesia is rarely used, but is still described in the manufacturer label.

General anesthesia without additional anesthetic agents: IV: 50 to 100 mcg/kg with oxygen and skeletal muscle relaxant.

Fentanyl side effects

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

• drowsiness
• stomach pain
• gas
• heartburn
• weight loss
• difficulty urinating
• changes in vision
• anxiety
• depression
• unusual thinking
• unusual dreams
• difficulty falling asleep or staying asleep
• dry mouth
• sudden reddening of the face, neck, or upper chest
• uncontrollable shaking of a part of the body
• back pain
• chest pain
• pain, sores, or irritation in the mouth in the area where you placed the medication
• swelling of the hands, arms, feet, ankles, or lower legs

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• changes in heartbeat
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• seizures
• hives
• rash
• itching

If you experience any of these symptoms, stop using fentanyl and call your doctor immediately or get emergency medical treatment:

• slow, shallow breathing
• decreased urge to breathe
• difficulty breathing or swallowing
• extreme drowsiness
• dizziness
• confusion
• fainting

Fentanyl may cause other side effects. Call your doctor if you have any unusual problems while using fentanyl.

Hydrocodone

Hydrocodone is an opioid pain medication that is used to relieve severe pain. Extended-release (long-acting) forms of hydrocodone are used for around-the-clock treatment of severe pain. Hydrocodone is only used to treat people who are expected to need medication to relieve severe pain around-the-clock for a long time and who cannot be treated with other medications or treatments. Hydrocodone extended-release (long-acting) capsules or extended-release tablets should not be used to treat pain that can be controlled by medication that is taken as needed. Hydrocodone is available only with your doctor’s prescription. Hysingla and Zohydro are available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

Hydrocodone comes as an extended-release (long-acting) capsule and an extended-release (long-acting) tablet to take by mouth. The extended-release capsule is usually taken once every 12 hours. The extended-release tablet is usually taken once daily. Take hydrocodone 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 hydrocodone exactly as directed by your doctor.

Swallow the extended-release capsules or extended-release tablets one at a time with plenty of water. Swallow each capsule or tablet as soon as you put it in your mouth. Do not presoak, wet, or lick the extended-release tablets before you put them in your mouth.

Your doctor will probably start you on a low dose of hydrocodone and may gradually increase your dose, not more than once every 3 to 7 days if needed to control your pain. After your take hydrocodone for a period of time, your body may become used to the medication. If this happens, your doctor may increase your dose of hydrocodone or may prescribe a different medication to help control your pain. Talk to your doctor about how you are feeling during your treatment with hydrocodone.

Do not stop taking hydrocodone without talking to your doctor. If you suddenly stop taking hydrocodone, you may experience withdrawal symptoms such as restlessness, teary eyes, runny nose, yawning, sweating, chills, hair standing on end, muscle pain, widened pupils (black circles in the middle of the eyes), irritability, anxiety, back or joint pain, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, loss of appetite, vomiting, diarrhea, fast breathing, or fast heartbeat. Your doctor will probably decrease your dose gradually.

Hydrocodone special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse or
• Brain tumor, history of or
• Breathing or lung problems (eg, apnea, low oxygen levels) or
• Chronic obstructive pulmonary disease (COPD) or
• Congestive heart failure or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially with narcotics abuse or dependence, history of or
• Electrolyte imbalance or
• Gallbladder problems or
• Head injury, history of or
• Heart rhythm problems (eg, congenital long QT syndrome, slow heartbeat) or
• Increased pressure in the head or
• Mental health problems, history of or
• Stomach or bowel problems or
• Trouble swallowing or
• Weakened immune system—Use with caution. May increase risk for more serious side effects.
• Asthma, acute or severe or
• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus), known or suspected—Should not be used in patients with these conditions.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Before taking hydrocodone:

• tell your doctor and pharmacist if you are allergic to hydrocodone, any other medications, or any of the ingredients in hydrocodone extended-release capsules or extended-release tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following medications: antihistamines (found in cough and cold medications); amiodarone (Nexterone, Pacerone); azithromycin (Zithromax, Zmax); butorphanol; chlorpromazine; citalopram (Celexa); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); dronedarone (Multaq); haloperidol (Haldol); laxatives such as lactulose (Cholac, Constulose, Enulose, others); levofloxacin (Levaquin); lithium (Lithobid); medications for irritable bowel disease, Parkinson’s disease, ulcers, and urinary problems; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; pentazocine (Talwin); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); trazodone (Oleptro); or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following medications or have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with hydrocodone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, a blockage or narrowing of your stomach or intestines, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take hydrocodone.
• tell your doctor if you have or have ever had low blood pressure, difficulty urinating, seizures, or thyroid, gall bladder, pancreas, liver, or kidney disease. If you are taking the extended-release tablets, also tell your doctor if you have or have ever had difficulty swallowing, colon cancer (cancer that begins in the large intestine), esophageal cancer (cancer that begins in the tube that connects the mouth and stomach), heart failure (HF; condition in which the heart cannot pump enough blood to other parts of the body), or heart rhythm problems such long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death).
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking hydrocodone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking hydrocodone.
• you should know that hydrocodone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that hydrocodone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking hydrocodone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that hydrocodone may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

Hydrocodone 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 hydrocodone, 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 hydrocodone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using hydrocodone 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.

• Abametapir
• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asenapine
• Atazanavir
• Baclofen
• Benperidol
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Dasabuvir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Enzalutamide
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Fexinidazole
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ombitasvir
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paritaprevir
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Saquinavir
• Scopolamine
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using hydrocodone 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 hydrocodone, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Hydrocodone uses

Hydrocodone is used to relieve pain in opioid-tolerant patients severe enough to require around-the-clock pain relief for a long period of time. It should not be used if you need pain medicine for just a short time, such as when recovering from surgery. Do not use hydrocodone to relieve mild pain. Hydrocodone should not be used to treat pain that you only have once in a while or “as needed”.

When hydrocodone is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Hydrocodone dosage

The dose of hydrocodone 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 hydrocodone. 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 severe pain

• For oral dosage form (extended-release capsules):
  • Patients who are not taking narcotic medicines:
    • Adults—At first, 10 milligrams (mg) every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—The capsule is given every 12 hours. Your doctor will determine your dose and adjust the dose as needed.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • Patients who are not taking narcotic medicines:
    • Adults—
      • Hysingla® ER: At first, 20 milligrams (mg) every 24 hours. Your doctor may adjust your dose as needed.
      • Vantrela™: At first, 15 mg every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—
      • Hysingla® ER: The tablet is given every 24 hours. Your doctor will determine your dose and adjust the dose as needed.
      • Vantrela™: The tablet is given every 12 hours. Your doctor will determine your dose and adjust the dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed dose

Skip the missed dose and continue your regular dosing schedule. Do not take more than one dose of hydrocodone extended-release capsules in 12 hours or extended-release tablets in 24 hours.

Hydrocodone side effects

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

• stomach pain
• dry mouth
• tiredness
• headache
• back pain
• muscle tightening
• difficult, frequent, or painful urination
• ringing in the ears
• difficulty falling asleep or staying asleep
• foot, leg, or ankle swelling
• uncontrollable shaking of a part of the body

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, call your doctor immediately or get emergency medical treatment:

• chest pain
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• swelling of your eyes, face, lips, tongue, or throat
• hoarseness
• changes in heartbeat
• hives
• itching
• difficulty swallowing or breathing

Hydrocodone may cause other side effects. Call your doctor if you have any unusual problems while taking hydrocodone.

Hydromorphone

Hydromorphone is an opioid medication used to treat moderate to severe pain. The extended-release form of hydromorphone is for around-the-clock treatment of moderate to severe pain, not for use on an as-needed basis for pain. Hydromorphone extended-release tablets should only be used to treat people who are tolerant (used to the effects of the medication) to opioid medications because they have taken this type of medication for at least one week and should not be used to treat mild or moderate pain, short-term pain, pain after an operation or medical or dental procedure, or pain that can be controlled by medication that is taken as needed.

Hydromorphone is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

Hydromorphone comes as a liquid, a tablet, and an extended-release (long-acting) tablet to take by mouth. The liquid is usually taken every 3 to 6 hours and the tablets are usually taken every 4 to 6 hours. The extended-release tablets are taken once daily with or without food. Take hydromorphone 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 hydromorphone exactly as directed.

Do not allow the hydromorphone liquid to touch your skin or clothing. If such contact occurs, remove any clothes exposed to the oral liquid and wash your skin thoroughly with cool water.

Your doctor may start you on a low dose of hydromorphone and gradually increase your dose, not more often than once every 3 to 4 days. Your doctor may decrease your dose if you experience side effects. Tell your doctor if you feel that your pain is not controlled or if you experience side effects during your treatment with hydromorphone. Do not change the dose of your medication without talking to your doctor.

Do not stop taking hydromorphone without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking hydromorphone, you may experience withdrawal symptoms including restlessness, teary eyes, runny nose, yawning, sweating, chills, hair standing on end, muscle or joint pain, widening of the pupils (black circles in the middle of the eyes), irritability, anxiety, backache, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, loss of appetite, vomiting, diarrhea, fast breathing, or fast heartbeat. Your doctor will probably decrease your dose gradually. If you do not take hydromorphone extended-release tablets for longer than 3 days for any reason, talk to your doctor before you start taking the medication again.

Hydromorphone special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor or
• Breathing or lung problems (eg, apnea, low oxygen levels) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially narcotic abuse or dependence, history of or
• Gallbladder disease or
• Head injury, history of or
• Hypothyroidism (an underactive thyroid) or
• Mental health problems, or history of or
• Obesity, severe or
• Prostatic hypertrophy (enlarged prostate, BPH) or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Allergy to sulfites or
• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Narrowing of the stomach or bowels (“blind loops”) or
• Stomach or bowel blockage (eg, paralytic ileus), known or suspected—Should not be used in patients with these conditions.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Before taking hydromorphone:

• tell your doctor and pharmacist if you are allergic to hydromorphone, any other medications, sulfites, or any of the ingredients in hydromorphone tablets, solution, or extended-release tablets. Ask your pharmacist or check the Medication Guide 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 the medications listed in the IMPORTANT WARNING section and any of the following: buprenorphine (Buprenex, Butrans, in Suboxone, in Zubsolv, others); butorphanol; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); ipratropium (Atrovent); medications for glaucoma, irritable bowel disease, Parkinson’s disease, ulcers, and urinary problems; lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; pentazocine (Talwin); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); trazodone (Oleptro); and tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving any of the following monoamine oxidase (MAO) inhibitors or have stopped taking them within the past 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with hydromorphone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have any of the conditions listed in the IMPORTANT WARNING section or paralytic ileus (condition in which food does not move through the intestines), or a blockage in the stomach or intestines. Your doctor may tell you not to take hydromorphone.
• if you will be taking the extended-release tablets, also tell your doctor if you have ever had surgery that caused a change in the way food moves through your stomach or intestines or if you have any condition that cause narrowing of the esophagus (tube that carries food from the mouth to the stomach), stomach, or intestines such as cystic fibrosis (a condition that causes the body to produce thick, sticky mucus that may clog the pancreas, lungs, and other parts of the body), peritonitis (inflammation of the lining of the abdomen (stomach area), Meckel’s diverticulum (a bulge in the lining of the small intestine that is present at birth), chronic intestinal pseudo-obstruction (condition in which the muscles in the intestine do not move food smoothly through the intestine), or inflammatory bowel disease (IBD; a group of conditions that cause inflammation of the lining of the intestine. Your doctor may tell you not to take hydromorphone extended-release tablets.
• tell your doctor if you have or have ever had low blood pressure;Addison’s disease (condition in which the adrenal gland produces less hormone than normal); seizures; any condition that causes difficulty urinating, such as an enlarged prostate (a male reproductive gland) or urethral stricture (blockage of the tube that allows urine to leave the body); or gallbladder, pancreas, liver, thyroid, or kidney disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking hydromorphone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking hydromorphone.
• you should know that hydromorphone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that hydromorphone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that hydromorphone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking hydromorphone.

Hydromorphone 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 hydromorphone, 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 hydromorphone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using hydromorphone 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Citalopram
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cocaine
• Codeine
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Escitalopram
• Esketamine
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lorazepam
• Lorcaserin
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Midazolam
• Milnacipran
• Mirtazapine
• Moclobemide
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naratriptan
• Nefazodone
• Nialamide
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Ozanimod
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Rizatriptan
• Scopolamine
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using hydromorphone 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 hydromorphone, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Hydromorphone uses

Hydromorphone is used for the short-term relief of severe pain, where other pain medicines have been ineffective or cannot be used. It is more potent than morphine and should only be used under specialist medical supervision.

Hydromorphone should also be used only when other forms of pain relief have not been successful in managing pain.

Hydromorphone extended-release tablets are used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. Hydromorphone extended-release tablets should only be used to treat people who are tolerant (used to the effects of the medication) to opioid medications because they have taken this type of medication for at least one week and should not be used to treat mild or moderate pain, short-term pain, pain after an operation or medical or dental procedure, or pain that can be controlled by medication that is taken as needed.

Hydromorphone dosage

The dose of hydromorphone 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 hydromorphone. 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 oral dosage form (extended-release capsules)

• For moderate to severe pain:
  • For patients switching from other narcotic medicines:
    • Adults—The capsule is given once a day. Your first dose will depend on the amount of the other narcotic you have been taking. Your doctor will determine your dose and adjust the dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets)

• For moderate to severe pain:
  • For patients switching from regular hydromorphone forms:
    • Adults—The tablet is given once a day. The total amount of milligrams (mg) per day is the same as the total amount of regular hydromorphone that is taken per day.
    • Children—Use and dose must be determined by your doctor.
  • For patients switching from other narcotic medicines:
    • Adults—The tablet is given once a day. Your first dose will depend on the amount of the other narcotic you have been taking. Your doctor will determine your dose and adjust the dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (solution)

• For moderate to severe pain:
  • Adults—At first, 2.5 to 10 milliliters (mL) or one-half to two teaspoons every 3 to 6 hours as needed. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

• For moderate to severe pain:
  • Adults—At first, 2 to 4 milligrams (mg) every 4 to 6 hours. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

Missed dose

If you are taking the tablets or solution, 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.

If you are taking the extended-release tablets, skip the missed dose and continue your regular dosing schedule. Do not take more than one dose of the extended-release tablets in 24 hours.

Hydromorphone side effects

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

• headache
• difficulty falling asleep or staying asleep
• dry mouth
• lightheadedness
• drowsiness
• heavy sweating
• muscle, back or joint pain
• stomach pain
• anxiety
• flushing
• itching
• depression

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• rash
• hives
• swelling of the eyes, face, lips, tongue, mouth, throat, arms, hands, feet, ankles, or lower legs
• difficulty breathing or swallowing
• hoarseness
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• seizures
• chest pain
• extreme drowsiness
• fainting
• lightheadedness when changing positions

Hydromorphone may cause other side effects. Call your doctor if you have any unusual problems while you are taking hydromorphone.

Meperidine

Meperidine is an opioid medication used to treat moderate-to-severe pain. Meperidine should not be used to relieve chronic (long-lasting or recurrent) pain. Meperidine is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

When meperidine is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Meperidine comes as a tablet and a syrup (liquid) to take by mouth. It is usually taken with or without food every 3 to 4 hours as needed for pain. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

If you are taking the meperidine tablets, swallow them whole; do not chew, break, or crush them. Swallow each tablet right after you put it in your mouth.

If you are taking meperidine syrup, use a dose-measuring spoon or cup to measure the correct amount of liquid for each dose, not a regular household spoon. Mix your dose with half a glass of water and swallow the mixture. Swallowing undiluted meperidine syrup may numb the mouth.

Your doctor will probably adjust your dose of meperidine during your treatment. Be sure to tell your doctor about any pain and side effects you experience while taking this medication. This will help your doctor find the dose that is best for you.

If you have taken meperidine for longer than a few weeks, do not stop taking the medication without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking meperidine, you may experience withdrawal symptoms. Withdrawal symptoms may include restlessness, watery eyes, stuffy nose, yawning, sweating, chills, muscle pain, irritability, nervousness, stomach pain, upset stomach, vomiting, loss of appetite, diarrhea, fast breathing, fast heartbeat, and back pain.

Meperidine special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain problems (including tumors or increased intracranial pressure) or
• Breathing or lung problems (eg, COPD, hypoxia, sleep apnea) or
• Central nervous system (CNS) depression or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate or
• Gallbladder disease or
• Head injuries, history of or
• Hypothyroidism (an underactive thyroid) or
• Kyphoscoliosis (severe curvature of the spine with breathing problems) or
• Mental illness, history of or
• Pancreatitis (swelling of the pancreas) or
• Pheochromocytoma (adrenal gland tumor) or
• Sickle cell anemia (inherited blood disorder) or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Heart rhythm problems (eg, atrial flutter, tachycardia) or
• Hypotension (low blood pressure) or
• Hypovolemia (low blood volume) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

Before taking meperidine:

• tell your doctor and pharmacist if you are allergic to meperidine, any other medications, or any of the ingredients in meperidine tablets or syrup. Ask your doctor or 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 any of the following: acyclovir (Zovirax); butorphanol; cimetidine (Tagamet); medications for vomiting and seizures; certain medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); 5-HT3 receptor antagonists such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, Selfemra), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq, Khedezla), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); and tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past 2 weeks: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl), and tranylcypromine (Parnate). 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 any of the conditions mentioned in the IMPORTANT WARNING section or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take meperidine.
• tell your doctor if you have or have ever had pheochromocytoma (a type of tumor); difficulty urinating; irregular heartbeat; seizures; stomach problems; or thyroid, pancreas, gallbladder, liver, kidney, or lung disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking meperidine.
• talk to your doctor about the risks and benefits of taking meperidine if you are 65 years of age or older. Older adults should not usually take meperidine because it is not as safe or as effective as other medications that can be used to treat the same condition.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking meperidine.
• you should know that meperidine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that meperidine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking meperidine. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

Meperidine 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 meperidine, 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 meperidine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Samidorphan
• Selegiline
• Toloxatone
• Tranylcypromine

Using meperidine 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asenapine
• Atazanavir
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dixyrazine
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Enzalutamide
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Metopimazine
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Nevirapine
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Prochlorperazine
• Promazine
• Promethazine
• Propiomazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Remifentanil
• Remimazolam
• Remoxipride
• Rifabutin
• Rifampin
• Rifapentine
• Rizatriptan
• Saquinavir
• Scopolamine
• Secobarbital
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioproperazine
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using meperidine 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.

• Isoniazid
• Ritonavir

Other interactions

Using meperidine 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 meperidine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Using meperidine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use meperidine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Meperidine uses

Meperidine is used to relieve moderate to severe pain to require opioid treatment and when other pain medicines did not work well enough or cannot be tolerated. It belongs to the group of medicines called narcotic analgesics (pain medicines). Meperidine acts on the central nervous system (CNS) to relieve pain. Meperidine should not be used to relieve chronic (long-lasting or recurrent) pain.

Meperidine dosage

The dose of meperidine 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 meperidine. 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 oral dosage forms (solution or tablets)

• For moderate to severe pain:
  • Adults—50 to 150 milligrams (mg) every 3 or 4 hours as needed.
  • Children 1 year of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 1.1 to 1.8 milligrams (mg) per kilogram (kg) of body weight per dose given every 3 or 4 hours as needed.
  • Children younger than 1 year of age—Use and dose must be determined by your doctor.

Missed dose

Meperidine is usually taken as needed. If your doctor has told you to take meperidine 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.

Meperidine side effects

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

• lightheadedness
• dizziness
• weakness
• headache
• extreme calm
• mood changes
• nausea
• vomiting
• stomach pain or cramps
• constipation
• dry mouth
• flushing
• sweating
• changes in vision

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them or those listed in the IMPORTANT WARNING section, call your doctor immediately:

• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• slow or difficult breathing
• shaking hands that you cannot control
• seizures
• changes in heartbeat
• difficulty urinating
• fainting
• rash
• hives

Meperidine may cause other side effects. Call your doctor if you have any unusual problems while taking meperidine.

Methadone

Methadone is an opiate (narcotic) analgesic medication that is used as a pain reliever and as part of drug addiction detoxification and maintenance programs. Methadone reduces withdrawal symptoms in people addicted to heroin or other narcotic drugs without causing the “high” associated with the drug addiction. Methadone is also used for around-the-clock treatment of severe pain. Methadone is not for use on an as-needed basis for pain. Methadone is available only with your doctor’s prescription.

Methadone works to treat pain by changing the way the brain and nervous system respond to pain. It works to treat people who were addicted to opiate drugs by producing similar effects and preventing withdrawal symptoms in people who have stopped using these drugs.

Methadone comes as a tablet, a dispersible (can be dissolved in liquid) tablet, a solution (liquid), and a concentrated solution to take by mouth. When methadone is used to relieve pain, it may be taken every 8 to 12 hours. If you take methadone as part of a treatment program, your doctor will prescribe the dosing schedule that is best for you. Follow the directions on your prescription label carefully and ask your doctor or pharmacist to explain any part you do not understand. Take methadone exactly as directed.

If you are using the dispersible tablets, do not chew or swallow before mixing the tablet in a liquid. If your doctor has told you to take only part of a tablet, break the tablet carefully along the lines that have been scored into it. Place the tablet or piece of the tablet in at least 120 mL (4 ounces) of water, orange juice, Tang®, citrus flavors of Kool-Aid®, or a citrus fruit drink to dissolve. Drink the entire mixture right away. If some tablet residue remains in the cup after you drink the mixture, add a small amount of liquid to the cup and drink it all.

Your doctor may change your dose of methadone during your treatment. Your doctor may decrease your dose or tell you to take methadone less often as your treatment continues. If you experience pain during your treatment, your doctor may increase your dose or may prescribe an additional medication to control your pain. Talk to your doctor about how you are feeling during your treatment with methadone. Do not take extra doses of methadone or take doses of methadone earlier than they are scheduled even if you experience pain.

Do not stop taking methadone without talking to your doctor. Your doctor will probably want to decrease your dose gradually. If you suddenly stop taking methadone, you may experience withdrawal symptoms such as restlessness, teary eyes, runny nose, yawning, sweating, chills, muscle pain, widened pupils (black circles in the middle of the eyes), irritability, anxiety, backache, joint pain, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, decreased appetite, vomiting, or diarrhea.

Methadone special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor or
• Breathing or lung problems (eg, COPD, hypercapnia, hypoxia, apnea, sleep apnea) or
• CNS depression, history of or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially narcotic abuse or dependence, or history of or
• Gallbladder disease or
• Head injuries, history of or
• Heart disease (eg, cardiac hypertrophy) or
• Heart rhythm problems (eg, arrhythmia, long QT syndrome), or history of or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood) or
• Increased pressure in your head or
• Stomach or bowel problems or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

Before taking methadone:

• tell your doctor and pharmacist if you are allergic to methadone, any other medications, or any of the ingredients in the methadone product you plan to take. Ask your doctor or pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antihistamines; buprenorphine (Suboxone, in Zubsolv); butorphanol; carbamazepine (Cabatrol, Equetro, Tegretol, others); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); medications for glaucoma, irritable bowel disease, Parkinson’s disease, ulcers, and urinary problems; certain medications for HIV including abacavir (Ziagen, in Trizivir), darunavir (Prezista), didanosine (Videx), efavirenz (Sustiva, in Atripla), lopinavir (in Kaletra), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra), saquinavir (Invirase), stavudine (Zerit), tipranavir (Aptivus), and zidovudine (Retrovir, in Combivir); lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; naloxone (Evzio, Narcan, in Zubsolv); naltrexone (ReVia, Vivitrol, in Embeda); pentazocine (Talwin); phenobarbital; phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), and paroxetine (Brisdelle, Prozac, Pexeva); serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella); and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet); and trazodone (Oleptro). Also tell your doctor or pharmacist if you are taking or receiving the following medications or have stopped taking them in the past 14 days: monoamine oxidase (MAO) inhibitors including isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelpar), and tranylcypromine (Parnate). Many other medications may also interact with methadone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section or have or have ever had a blockage in your intestine or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you that you should not take methadone.
• tell your doctor if you have or have ever had difficulty urinating; an enlarged prostate (a male reproductive gland); Addison’s disease (a condition in which the adrenal gland does not make enough of certain natural substances); seizures; or thyroid, pancreas, gallbladder, liver, or kidney disease.
• tell your doctor if you are breastfeeding. If you breastfeed during your treatment with methadone, your baby may receive some methadone in breastmilk. Watch your baby closely for any changes in behavior or breathing, especially when you start taking methadone. If your baby develops any of these symptoms, call your baby’s doctor immediately or get emergency medical help: unusual sleepiness, difficulty breastfeeding, difficulty breathing, or limpness. Talk to your baby’s doctor when you are ready to wean your baby. You will need to wean your baby gradually so that your baby will not develop withdrawal symptoms when he or she stops receiving methadone in breastmilk.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking methadone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking methadone.
• 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.
• you should know that methadone may cause dizziness when you get up too quickly from a lying position. This is more common when you first start taking methadone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that methadone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking methadone.

Special dietary instructions

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking methadone.

Methadone 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 methadone, 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 methadone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bepridil
• Cisapride
• Dronedarone
• Fluconazole
• Itraconazole
• Ketoconazole
• Mesoridazine
• Nalmefene
• Naltrexone
• Nelfinavir
• Pimozide
• Piperaquine
• Posaconazole
• Rasagiline
• Safinamide
• Samidorphan
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using methadone 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.

• Abametapir
• Acepromazine
• Alfentanil
• Alfuzosin
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anagrelide
• Anileridine
• Apomorphine
• Aprepitant
• Aripiprazole
• Aripiprazole Lauroxil
• Armodafinil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Azithromycin
• Baclofen
• Bedaquiline
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buserelin
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Cariprazine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clofazimine
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Dabrafenib
• Dantrolene
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Ebastine
• Eletriptan
• Encorafenib
• Enflurane
• Entrectinib
• Enzalutamide
• Eribulin
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Famotidine
• Felbamate
• Fenfluramine
• Fentanyl
• Fexinidazole
• Fingolimod
• Flecainide
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Formoterol
• Fosaprepitant
• Foscarnet
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Fostemsavir
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halazepam
• Halofantrine
• Haloperidol
• Halothane
• Hexobarbital
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroquinidine
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibutilide
• Idelalisib
• Iloperidone
• Imatinib
• Imipramine
• Indinavir
• Inotuzumab Ozogamicin
• Iproniazid
• Isocarboxazid
• Isoflurane
• Ivabradine
• Ivacaftor
• Ivosidenib
• Ketamine
• Ketazolam
• Ketobemidone
• Lapatinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Lenvatinib
• Levocetirizine
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Lumefantrine
• Lurasidone
• Macimorelin
• Magnesium Oxybate
• Meclizine
• Mefloquine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Metaxalone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Metoclopramide
• Metronidazole
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Mizolastine
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Netupitant
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Paliperidone
• Palonosetron
• Panobinostat
• Papaveretum
• Papaverine
• Paregoric
• Paroxetine
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pipamperone
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Ponesimod
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Probucol
• Procainamide
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propafenone
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinidine
• Quinine
• Ramelteon
• Ranitidine
• Ranolazine
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Risperidone
• Ritonavir
• Rizatriptan
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Siponimod
• Sodium Oxybate
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John’s Wort
• Sufentanil
• Sulpiride
• Sunitinib
• Suvorexant
• Tacrolimus
• Tamoxifen
• Tapentadol
• Telaprevir
• Telavancin
• Telithromycin
• Temazepam
• Tetrabenazine
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thiothixene
• Tianeptine
• Tilidine
• Tipranavir
• Tizanidine
• Tolonium Chloride
• Topiramate
• Toremifene
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Triclabendazole
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Triptorelin
• Tryptophan
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Verapamil
• Vilanterol
• Vilazodone
• Vinflunine
• Voclosporin
• Voriconazole
• Vorinostat
• Vortioxetine
• Zaleplon
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine
• Zuclopenthixol

Using methadone 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.

• Abacavir
• Atazanavir
• Didanosine
• Etravirine
• Fosamprenavir
• Nevirapine
• Peginterferon Alfa-2a
• Stavudine
• Zidovudine

Methadone uses

Methadone is prescribed for the treatment of heroin and other opioid dependencies, and for severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications.

Methadone also is used to prevent withdrawal symptoms in patients who were addicted to opiate drugs and are enrolled in treatment programs in order to stop taking or continue not taking the drugs.

Methadone is used to treat moderate to severe pain when around-the-clock pain relief is needed for a long period of time. This medicine should not be used to treat pain that you only have once in a while or “as needed”. Because of the risks associated with opioid use, methadone should only be used for pain relief in people who are unable to take non-opioid pain-relief medicines, or in circumstances when pain cannot be managed with other options.

Methadone is also used together with medical supervision and counseling to treat opioid addiction (eg, heroin or other morphine-like drugs).

Methadone dosage

The dose of methadone 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 methadone. 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 oral dosage form (tablets)

• For pain:
  • For patients taking Dolophine® as the first pain medicine:
    • Adults—At first, 2.5 milligrams (mg) every 8 to 12 hours. Your doctor may adjust your dose as needed. Do not take more than your prescribed dose in 24 hours.
    • Children—Use and dose must be determined by your doctor.
  • For patients switching from other opioids to Dolophine®:
    • Adults—The dose must be determined by your doctor based on the previous dose of opioid medicine. The dose is given every 8 or 12 hours. Your doctor may adjust your dose as needed. Do not take more than your prescribed dose in 24 hours.
    • Children—Use and dose must be determined by your doctor.
• For opioid addiction:
  • Adults—At first, 20 to 30 milligrams (mg) taken as a single dose per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day. Do not take more than your prescribed dose in 24 hours.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (liquid)

• For opioid addiction:
  • Adults—At first, 20 to 30 milligrams (mg) taken as a single dose per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day. Do not take more than your prescribed dose in 24 hours.
  • Children—Use and dose must be determined by your doctor.

Missed dose

If your doctor has told you to take methadone for pain, take the missed dose as soon as you remember it and then continue your regular dosing schedule. 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.

If you are taking methadone to treat opioid addiction, skip the missed dose and take the next dose the next day as scheduled. Do not take a double dose to make up for a missed one.

Methadone side effects

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

• headache
• weight gain
• stomach pain
• dry mouth
• sore tongue
• flushing
• difficulty urinating
• mood changes
• vision problems
• difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical help:

• seizures
• itching
• hives
• rash
• swelling of the eyes, face, mouth, tongue, or throat
• hoarseness
• difficulty breathing or swallowing
• extreme drowsiness
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire

Methadone may cause other side effects. Call your doctor if you have any unusual problems while you are taking methadone.

Morphine

Morphine is an opioid medication that is used to treat moderate to severe pain, such as pain caused by a major trauma or surgery, labor pain in childbirth or cancer pain. The extended-release form of morphine is for around-the-clock treatment of pain that cannot be controlled by the use of other pain medications. Extended-release morphine is not for use on an as-needed basis for pain. Short-acting formulations are taken as needed for pain.

Morphine should only be used where other forms of pain relief have not been successful in managing pain or are not tolerated. Morphine is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

Morphine comes as a solution (liquid), an extended-release (long-acting) tablet, and as an extended-release (long-acting) capsule to take by mouth. The oral solution is usually taken every 4 hours as needed for pain. MS Contin brand and Arymo ER brand are extended-release tablets that are usually taken every 8 or every 12 hours. Morphabond brand extended-release tablets are usually taken every 12 hours. Kadian brand extended-release capsules are usually taken with or without food every 12 hours or every 24 hours. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

If you are taking morphine solution, use the dosing cup or syringe that comes with the medication to measure your dose. Be sure that you know how many milliliters of the liquid you should take. Ask your pharmacist if you have any question about how much medication you should take or how to use the dosing cup or syringe.

If you are taking Kadian brand extended-release capsules and you have a gastrostomy tube (surgically inserted feeding tube), ask your doctor or pharmacist how to administer the medication through your tube.

If you are unable to swallow the extended-release capsules (Kadian), you can carefully open a capsule, sprinkle all of the beads that it contains on a spoonful of cold or room temperature applesauce, and swallow the entire mixture immediately without chewing or crushing the beads. Then rinse your mouth with a little water and swallow the water to be sure that you have swallowed all the medication. Do not mix the beads into any other food. Do not save mixtures of medication and applesauce for later.

If you are taking the extended-release tablets (Arymo ER), swallow them one at a time with plenty of water. Swallow the extended-release tablets right after putting it in your mouth. Do not presoak, wet, or lick the extended-release tablets before you put them in your mouth.

Your doctor may start you on a low dose of morphine and gradually increase your dose until your pain is controlled. Your doctor may adjust your dose at any time during your treatment if your pain is not controlled. If you feel that your pain is not controlled, call your doctor. Do not change the dose of your medication without talking to your doctor.

Do not stop taking morphine without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop taking morphine, you may experience withdrawal symptoms such as restlessness; teary eyes; runny nose; yawning; irritability; anxiety; sweating; difficulty falling asleep or staying asleep; chills; back, muscle, or joint pain; nausea; vomiting; loss of appetite; diarrhea; stomach cramps; weakness; fast heartbeat; or fast breathing.

Morphine special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor, history of or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate (BPH, prostatic hypertrophy) or
• Gallbladder disease or gallstones or
• Head injuries, history of or
• Heart disease or
• Hypothyroidism (an underactive thyroid) or
• Hypovolemia (low blood volume) or
• Increased pressure in the head or
• Kyphoscoliosis (curvature of the spine with breathing problems) or
• Mental health problems, history of or
• Problems with passing urine or
• Stomach or bowel problems (eg, blockage) or
• Trouble swallowing or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Lung or breathing problems, severe (eg, asthma, respiratory depression) or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

Before taking morphine:

• tell your doctor and pharmacist if you are allergic to morphine, any other medications, or any of the inactive ingredients in the type of morphine product you plan to take. Ask your pharmacist or check the Medication Guide for a list of the inactive 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 the medications listed in the IMPORTANT WARNING section and any of the following: antihistamines (found in cold and allergy medications); buprenorphine (Belbuca, Butrans, in Suboxone, others); butorphanol; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); diuretics (‘water pills’); lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; pentazocine (Talwin); quinidine (in Nuedexta); 5HT3 serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet), trazodone (Oleptro); or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor if you are taking any of the following monoamine oxidase (MAO) inhibitors, or if you have stopped taking them within the past 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). Many other medications may also interact with morphine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take morphine.
• tell your doctor if you have or have ever had a blockage in your stomach or intestines; seizures; difficulty swallowing; prostatic hypertrophy (enlargement of a male reproductive gland); urinary problems; low blood pressure; Addison’s disease (condition in which the adrenal gland does not make enough of certain natural substances) or liver, kidney, pancreas, thyroid, or gallbladder disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking morphine.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking morphine.
• 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.
• you should know that morphine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that morphine may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking morphine.

Morphine 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 morphine, 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 morphine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using morphine 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Azithromycin
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Captopril
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Carvedilol
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Cyclosporine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Erythromycin
• Escitalopram
• Esketamine
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Felodipine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketobemidone
• Ketoconazole
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Metoclopramide
• Midazolam
• Milnacipran
• Mirtazapine
• Moclobemide
• Molindone
• Moricizine
• Nalbuphine
• Nalorphine
• Naloxone
• Naratriptan
• Nefazodone
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Ozanimod
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quercetin
• Quetiapine
• Quinidine
• Ramelteon
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ritonavir
• Rizatriptan
• Scopolamine
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Simeprevir
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Sunitinib
• Suvorexant
• Tapentadol
• Telaprevir
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Ticagrelor
• Tilidine
• Tizanidine
• Tocophersolan
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using morphine 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.

• Esmolol
• Rifampin
• Somatostatin
• Yohimbine

Other interactions

Using morphine 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 morphine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Morphine uses

Morphine is used to relieve moderate to severe pain, such as pain caused by a major trauma or surgery, labor pain in childbirth or cancer pain.

Morphine should only be used where other forms of pain relief have not been successful in managing pain or are not tolerated.

Morphine extended-release tablets and capsules are only used to relieve severe (around-the-clock) pain that cannot be controlled by the use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat pain that can be controlled by medication that is taken as needed.

When morphine is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Morphine dosage

The dose of morphine 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 morphine. 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 oral dosage form (extended-release capsules)

• For moderate to severe pain:
  • Adults—The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose as needed.
    • Avinza®: The capsule is given every 24 hours.
    • Kadian®: The capsule is given every 12 or 24 hours.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets)

• For moderate to severe pain:
  • Adults—The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose as needed. The tablet is usually given every 8 or 12 hours.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (solution)

• For moderate to severe pain:
  • Adults—10 to 20 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

• For moderate to severe pain:
  • Adults—15 to 30 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

Missed dose

If you are taking morphine tablets or liquid, your doctor will probably tell you to take the medication as needed.

If you have been told to take scheduled doses of the tablets or liquid or if you are taking an extended-release product, take the missed dose as soon as you remember it, and do not take the next dose at your regularly scheduled time. Instead, allow the same amount of time that you usually allow between doses before taking your next dose. If you remember when 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.

Morphine side effects

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

• drowsiness
• stomach pain and cramps
• dry mouth
• headache
• nervousness
• mood changes
• small pupils (black circles in the middle of the eyes
• difficulty urinating or pain when urinating

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• blue or purple color to the skin
• changes in heartbeat
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• seizures
• extreme drowsiness
• fainting
• chest pain
• fever
• hives
• rash
• itching
• swelling of the eyes, face, mouth, lips or throat
• hoarseness
• difficulty breathing or swallowing

Morphine may cause other side effects. Call your doctor if you have any unusual problems while you are taking morphine.

Oxycodone

Oxycodone is an opioid pain medication that is used to treat moderate to severe pain when other pain medicines did not work well enough or cannot be tolerated. The extended-release form of oxycodone is for around-the-clock treatment of pain and should not be used on an as-needed basis for pain. Do not use oxycodone to relieve mild pain, or in situations when non-narcotic medication is effective. Oxycodone is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

When oxycodone is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Oxycodone comes as a solution (liquid), a concentrated solution, a tablet, a capsule, an extended-release (long-acting) tablet (Oxycontin) and an extended-release capsule (Xtampza ER) to take by mouth. The solution, concentrated solution, tablet, and capsule are taken usually with or without food every 4 to 6 hours, either as needed for pain or as regularly scheduled medications. The extended-release tablets (Oxycontin) are taken every 12 hours with or without food. The extended-release capsules (Xtampza ER) are taken every 12 hours with food; eat the same amount of food with each dose. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take oxycodone exactly as directed.

Oxycodone is also available in combination with acetaminophen (Oxycet, Percocet, Roxicet, Xartemis XR, others); aspirin (Percodan); and ibuprofen.

If you are taking Oxaydo brand tablets, swallow the tablets one at a time with plenty of water. Swallow the tablet or right after putting it in your mouth. Do not presoak, wet, or lick the tablets before you put them in your mouth. Do not chew or crush Oxaydo brand tablets. and do not give them through a nasogastric tube (NG tube; a tube threaded through the nose to deliver food and medication directly to the stomach).

If you have trouble swallowing extended-release capsules (Xtampza ER), you can carefully open the capsule and sprinkle the contents on soft foods such as applesauce, pudding, yogurt, ice cream, or jam, then consume the mixture immediately. Dispose of the empty capsule shells right away by flushing them down a toilet. Do not store the mixture for future use.

If you have a feeding tube, the extended-release capsule contents can be poured into the tube. Ask your doctor how you should take the medication and follow these directions carefully.

If you are taking the concentrated solution, your doctor may tell you to mix the medication in a small amount of juice or semisolid food such as pudding or applesauce. Follow these directions carefully. Swallow the mixture right away; do not store it for later use.

Your doctor will likely start you on a low dose of oxycodone and may increase this dose over time if your pain is not controlled. After you take oxycodone for a period of time, your body may become used to the medication. If this happens, your doctor may need to increase your dose to control your pain. Your doctor may decrease your dose if you experience side effects. Talk to your doctor about how you are feeling during your treatment with oxycodone.

Do not stop taking oxycodone without talking to your doctor. If you stop taking this medication suddenly, you may experience withdrawal symptoms such as restlessness, watery eyes, runny nose, sneezing, yawning, sweating, chills, muscle or joint aches or pains, weakness, irritability, anxiety, depression, difficulty falling asleep or staying asleep, cramps, nausea, vomiting, diarrhea, loss of appetite, fast heartbeat, and fast breathing. Your doctor will probably decrease your dose gradually.

Oxycodone special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing or lung problems (eg, hypoxia, COPD, sleep apnea) or
• Cancer of the esophagus or colon or
• CNS depression or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate (eg, BPH, prostatic hypertrophy) or
• Gallbladder disease or gallstones or
• Head injuries, history of or
• Hypothyroidism (an underactive thyroid) or
• Hypovolemia (low blood volume) or
• Increased pressure in the head or
• Kyphoscoliosis (curvature of the spine with breathing problems) or
• Problems with passing urine or
• Psychosis (mental disease) or
• Stomach or bowel problems (eg, esophageal or colon cancer with a small gastrointestinal lumen) or
• Trouble swallowing or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Asthma, acute or severe or
• Respiratory depression (serious breathing problem) or
• Stomach or bowel blockage (including paralytic ileus)—Should not be used in patients with these conditions.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease, severe or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Before taking oxycodone:

• tell your doctor and pharmacist if you are allergic to oxycodone, any other medications, or any of the ingredients in the oxycodone product you plan to take. Ask your pharmacist for a list of the ingredients.
• 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 medications listed in the IMPORTANT WARNING section and any of the following: antihistamines (found in cold and allergy medications); diuretics (‘water pills’); buprenorphine (Butrans, in Suboxone, in Zubsolv, others); butorphanol; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); medications for glaucoma, irritable bowel disease, and urinary problems; lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; naloxone (Evzio, Narcan, others); pentazocine (Talwin); 5-HT3 receptor antagonists such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet), trazodone (Oleptro); or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with oxycodone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take oxycodone.
• Also tell your doctor if you have or have ever had a blockage in your stomach or intestine; low blood pressure; seizures; Addison’s disease (condition in which the adrenal gland does not produce enough hormone); seizures; urethral stricture (blockage of the tube that allows urine to leave the body), enlarged prostate (a male reproductive gland), problems urinating; or heart, kidney, liver, pancreas, thyroid, or gall bladder disease. If you will be taking the extended-release tablets or extended-release capsules, also tell your doctor if you have or have ever had difficulty swallowing, diverticulitis (condition in which small pouches form in the intestines and become swollen and infected), colon cancer (cancer that begins in the large intestine), or esophageal cancer (cancer that begins in the tube that connects the mouth and stomach).
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking oxycodone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking oxycodone.
• you should know that this medication may make you drowsy. Do not drive a car, operate heavy machinery, or participate in any other possibly dangerous activities until you know how this medication affects you.
• you should know that oxycodone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To help avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that oxycodone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking oxycodone.

Oxycodone 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 oxycodone, 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 oxycodone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using oxycodone 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.

• Abiraterone Acetate
• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asciminib
• Asenapine
• Atazanavir
• Avacopan
• Baclofen
• Belzutifan
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Berotralstat
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Enzalutamide
• Erdafitinib
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Fexinidazole
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lanreotide
• Lasmiditan
• Lefamulin
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Lorlatinib
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirtazapine
• Mitotane
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Nalorphine
• Naloxone
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Octreotide
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Saquinavir
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• Sotorasib
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Tucatinib
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Voxelotor
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using oxycodone 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.

• St John’s Wort

Other interactions

Using oxycodone 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 oxycodone, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Oxycodone uses

Oxycodone is used to relieve moderate to severe pain. It should only be used when other forms of non-opioid pain relief have not been successful in managing pain or are not tolerated.

Oxycodone is not usually recommended for the treatment of chronic pain.

Oxycodone dosage

The dose of oxycodone 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 oxycodone. 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 oral dosage form (extended-release capsules)

• For severe pain:
  • Patients who are not taking narcotic medicines or are not opioid tolerant:
    • Adults—At first, 9 milligrams (mg) every 12 hours with food. Your doctor may adjust your dose as needed. However, the dose is usually not more than 288 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (capsules)

• For moderate to severe pain:
  • Patients who are not taking narcotic medicines:
    • Adults—At first, 5 to 15 milligrams (mg) every 4 to 6 hours as needed. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets)

• For moderate to severe pain:
  • Patients switching from regular oxycodone forms:
    • Adults—One tablet every 12 hours. The total amount of milligrams (mg) per day is the same as the total amount of regular oxycodone that is taken per day. The total amount per day will be given as 2 divided doses during the day. Your doctor may adjust your dose as needed.
    • Children 11 years of age and older—Dose must be determined by your doctor. The patient must already be receiving and tolerating opioids for at least 5 days in a row with a minimum of 20 mg per day of oxycodone or its equivalent for at least 2 days before taking OxyContin®.
    • Children younger than 11 years of age—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—One tablet every 12 hours. The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. The total amount per day will be given as 2 divided doses during the day. Your doctor may adjust your dose as needed.
    • Children 11 years of age and older—Dose must be determined by your doctor. The patient must already be receiving and tolerating opioids for at least 5 days in a row with a minimum of 20 mg per day of oxycodone or its equivalent for at least 2 days before taking OxyContin®.
    • Children younger than 11 years of age—Use and dose must be determined by your doctor.
  • Patients who are not taking narcotic medicines:
    • Adults—At first, 10 milligrams (mg) every 12 hours. Your doctor may adjust your dose as needed.
    • Older adults—At first, 3 to 5 milligrams (mg) every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (immediate-release tablets)

• For moderate to severe pain:
  • Patients who are not taking narcotic medicines:
    • Adults—At first, 5 to 15 milligrams (mg) every 4 to 6 hours as needed. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage forms (liquid concentrate or solution)

• For moderate to severe pain:
  • Adults—10 to 30 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage forms (solution)

• For moderate to severe pain:
  • Adults—5 to15 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

• For moderate to severe pain:
  • Adults—At first, 5 to 15 milligrams (mg) every 4 to 6 hours as needed. Your doctor may adjust your dose as needed and tolerated.
  • Children—Use and dose must be determined by your doctor.

Missed dose

If you are taking oxycodone on a regular 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. Do not take more than one dose of the extended-release tablets or capsules in 12 hours.

Oxycodone side effects

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

• dry mouth
• stomach pain
• drowsiness
• flushing
• headache
• mood changes

Some side effects can be serious. If you experience any of these symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical help:

• changes in heartbeat
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• chest pain
• hives
• itching
• rash
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• difficulty breathing or swallowing
• seizures
• extreme drowsiness
• lightheadedness when changing positions

Oxycodone may cause other side effects. Call your doctor if you have any unusual problems while you are taking oxycodone.

Oxymorphone

Oxymorphone is an opioid medicine that is used to treat moderate to severe pain. The extended-release form of oxymorphone is for around-the-clock treatment of pain and should not be used on an as-needed basis for pain. Oxymorphone is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

When oxymorphone is used for a long time, it may become habit-forming (causing mental or physical dependence). However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by reducing the dose gradually over a period of time before treatment is stopped completely.

Oxymorphone comes as a tablet and as an extended-release (long-acting) tablet to take by mouth on an empty stomach, at least 1 hour before or 2 hours after meals. It is usually taken every 4 to 6 hours. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take oxymorphone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the extended-release tablets whole; do not chew or crush them.

Your doctor will probably start you on a low dose of oxymorphone and gradually increase your dose until your pain is controlled. Your doctor may adjust your dose at any time during your treatment if your pain is not controlled. If you feel that your pain is not controlled, call your doctor. Do not change the dose of your medication without talking to your doctor.

Do not stop taking oxymorphone without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking oxymorphone, you may experience withdrawal symptoms such as restlessness; watery eyes; runny nose; yawning; sweating; chills; muscle, joint, or back pain; enlarged pupils (black circles in the centers of the eyes); irritability; anxiety; weakness; stomach cramps; difficulty falling asleep or staying asleep; nausea; vomiting; diarrhea; loss of appetite; fast heartbeat; and fast breathing.

Oxymorphone special precautions

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

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor or
• Breathing or lung problems (eg, COPD, hypoxia, sleep apnea) or
• Cor pulmonale (serious heart condition) or
• Depression, history of or
• Drug dependence, especially narcotic abuse or dependence, history of or
• Enlarged prostate (BPH, prostatic hypertrophy) or
• Head injuries, history of or
• Hypothyroidism (an underactive thyroid) or
• Kyphoscoliosis (curvature of spine with breathing problems) or
• Mental illness, or history of or
• Obesity, severe or
• Problems with passing urine or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Gallbladder disease or
• Hypotension (low blood pressure) or
• Hypovolemia (low blood volume) or
• Pancreatitis (swelling of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease or
• Liver disease, mild—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Liver disease, moderate to severe or
• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

Before taking oxymorphone:

• tell your doctor and pharmacist if you are allergic to oxymorphone, oxycodone (OxyContin, in Percocet, in Roxicet, others), codeine (in many pain relievers and cough medications), hydrocodone (Zohydro, in Anexsia, in Norco, in Reprexain, in Rezira, in Vicoprofen, in Vituz, others), dihydrocodeine (in Synalgos-DC), hydromorphone (Dilaudid, Exalgo), any other medications, or any of the ingredients in oxymorphone tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• 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 medications listed in the IMPORTANT WARNING section and any of the following: antihistamines; buprenorphine (Buprenex, Butrans, Zubsolv, in Suboxone); butorphanol (Stadol); cimetidine (Tagamet), diuretics (‘water pills’), ipratropium (Atrovent, in Combivent); medications for irritable bowel disease, motion sickness, Parkinson’s disease, or urinary problems; nalbuphine; and pentazocine (Talwin). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, liver disease, blockage in your stomach or intestine, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take oxymorphone.
• tell your doctor if you have or have ever seizures; problems urinating, or kidney, pancreas, thyroid, or gall bladder disease.
• tell your doctor if you are breastfeeding. If you are breastfeeding while taking oxymorphone, watch your baby closely for any unusual sleepiness, slowed breathing, or limpness.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking oxymorphone.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking oxymorphone.
• you should know that oxymorphone may make you drowsy, dizzy, or lightheaded. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that oxymorphone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that oxymorphone may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are using oxymorphone.

Oxymorphone 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 oxymorphone, 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 oxymorphone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

Using oxymorphone 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amifampridine
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Citalopram
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cocaine
• Codeine
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Escitalopram
• Esketamine
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lorazepam
• Lorcaserin
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Metoclopramide
• Midazolam
• Milnacipran
• Mirtazapine
• Moclobemide
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nalorphine
• Naloxone
• Naratriptan
• Nefazodone
• Nialamide
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Ozanimod
• Paliperidone
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Rizatriptan
• Scopolamine
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using oxymorphone 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 oxymorphone, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Oxymorphone uses

Oxymorphone is used to relieve moderate to severe pain in people whose pain is not controlled with other medications or when other pain medicines did not work well enough or cannot be tolerated. Do not use oxymorphone to relieve mild pain, or in situations where a non-narcotic medication is effective.

Oxymorphone extended-release tablets are used to relieve moderate to severe pain in patients requiring continuous, around-the-clock treatment for a long period of time, and should not be used if you need pain medicine for just a short time, such as when recovering from surgery. Oxymorphone extended-release should not be used to treat pain that you only have once in a while or “as needed”.

Oxymorphone dosage

The dose of oxymorphone 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 oxymorphone. 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 oral dosage form (extended-release tablets)

• For moderate to severe pain:
  • For patients who are not taking narcotic medicines:
    • Adults—At first, 5 milligrams (mg) every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • For patients switching from Opana® to Opana® ER:
    • Adults—At first, the dose is half of the total oral Opana® tablet that you are taking per day, every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • For patients switching from oxymorphone injection to Opana® ER:
    • Adults—At first, the dose is 10 times the total oxymorphone injection dose that you are receiving per day given in 2 divided doses. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.
  • For patients switching from oral opioids to Opana® ER:
    • Adults—At first, the dose is half of the total daily dose that you are taking per day, every 12 hours. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

• For moderate to severe pain:
  • For patients who are not taking narcotic medicines:
    • Adults—At first, 10 to 20 milligrams (mg) every 4 to 6 hours per day. Your doctor may adjust your dose as needed.
    • Children—Use is not recommended.
  • For patients switching from oxymorphone injection to Opana®:
    • Adults—At first, the dose is 10 times the total oxymorphone injection dose that you are receiving per day, divided into 4 to 6 equal doses. Your doctor may adjust your dose as needed.
    • Children—Use is not recommended.
  • For patients switching from oral opioids to Opana®:
    • Adults—At first, the dose is half of the total daily dose that you are taking per day, divided into 4 to 6 equal doses, every 4 to 6 hours. Your doctor may adjust your dose as needed.
    • Children—Use is not recommended.

Missed 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 one.

Oxymorphone side effects

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

• dry mouth
• stomach pain or swelling
• nausea
• vomiting
• gas
• excessive sweating
• flushing
• fast heartbeat
• red eyes
• headache
• feeling anxious or confused
• itching

Some side effects can be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately:

• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• changes in heartbeat
• seizures
• rash, hives, itching, nausea, vomiting, hoarseness, difficulty breathing or swallowing, chest pain. or swelling of the hands, eyes, face, lips, mouth, tongue or throat
• extreme drowsiness
• fainting

Oxymorphone may cause other side effects. Call your doctor if you have any unusual problems while taking oxymorphone.

Tapentadol

Tapentadol is an opioid pain medication that is used to treat moderate to severe pain to require opioid treatment and when other pain medicines did not work well enough or cannot be tolerated. Tapentadol extended-release form (Nucynta ER) is for around-the-clock treatment of pain that is not controlled by other medicines. The extended-release tablet is used to treat severe pain, including pain caused by nerve damage from diabetes. The extended-release form of tapentadol is not for use on an “as needed” basis for pain.

Tapentadol is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

When tapentadol is used for a long time, it may become habit-forming (causing mental or physical dependence). However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

Tapentadol comes as a tablet and an extended-release (long acting) tablet to take by mouth. The tablets are usually taken with or without food every 4 to 6 hours as needed. If you are taking tapentadol tablets, your doctor may tell you that you may take a second dose as soon as 1 hour after the first dose on your first day of treatment if needed to treat your pain. Do not take extra doses at any other time during your treatment and do not ever take extra doses of the extended-release tablets. The extended-release tablets are taken once every 12 hours. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tapentadol exactly as directed.

If you are taking the extended-release tablets, swallow them one at a time with plenty of water. Swallow each tablet right after you put it in your mouth.

Your doctor will probably start you on a low dose of tapentadol and gradually increase your dose until your pain is controlled. Your doctor may adjust your dose at any time during your treatment if your pain is not controlled. If you feel that your pain is not controlled, call your doctor. Do not change the dose of your medication without talking to your doctor.

After you take tapentadol for a period of time, your body may become used to the medication. If this happens, your doctor may need to increase your dose of medication to control your pain. Talk to your doctor about how you are feeling during your treatment with tapentadol.

Do not stop taking tapentadol without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking tapentadol, you may experience withdrawal symptoms such as restlessness; anxiety; irritability; teary eyes; yawning; chills; sweating; difficulty falling asleep or staying asleep; shivering; uncontrollable shaking of a part of your body; muscle, back, or joint pain; weakness; nausea; vomiting; diarrhea; stomach cramps; loss of appetite; runny nose, sneezing, or coughing; hair on your skin standing on end; fast breathing; fast heartbeat; widening of the pupils (black circles in the middle of the eyes); or hallucinations (seeing things or hearing voices that do not exist).

Tapentadol special precautions

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

• Adrenal problems or
• Alcohol abuse, history of or
• Brain tumor, history of or
• Breathing or other lung problems (eg, COPD, sleep apnea) or
• Depression, history of or
• Drug abuse or dependence, history of or
• Gallbladder problems or
• Head injuries, history of or
• Increased pressure in the head or
• Kyphoscoliosis (severe curvature of the spine that can cause breathing problems) or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.
• Asthma, acute or severe or
• Lung or breathing problems, severe or
• Stomach or bowel blockage (including paralytic ileus)—Should not be used in patients with these conditions.
• Hypotension (low blood pressure) or
• Pancreatitis (swelling of the pancreas) or
• Seizures or epilepsy, history of—Use with caution. May make these conditions worse.
• Kidney disease, severe or
• Liver disease, severe—Use is not recommended in patients with these conditions.
• Liver disease, moderate—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Before taking tapentadol:

• tell your doctor and pharmacist if you are allergic to tapentadol, or any other medications, or any of the ingredients in tapentadol tablets or extended-release tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor if you are taking the following medications or have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), rasagiline (Azilect), selegiline (Emsam, Eldepryl, Zelapar), and tranylcypromine (Parnate). Also tell your doctor if any of these medications are prescribed for you during your treatment with tapentadol. Your doctor will probably tell you not to take tapentadol if you are taking one or more of these 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 any of the following: antihistamines (in cough, cold, and allergy medications); buprenorphine (Buprenex, Butrans, in Suboxone, in Zubsolv); butorphanol; cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); medications for irritable bowel disease, motion sickness, Parkinson’s disease, ulcers, or urinary problems; lithium (Lithobid); medications for migraines such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); nalbuphine; pentazocine (Talwin); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Selfemra, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); tramadol (Conzip, Ultram, in Ultracet); trazodone; or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Surmontil, Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with tapentadol, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take tapentadol.
• tell your doctor if you have or have ever had a blockage in your stomach or intestines, any condition that causes difficulty urinating; or pancreas, gallbladder, kidney, thyroid, or liver disease.
• tell your doctor if you are breastfeeding.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking tapentadol.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tapentadol.
• you should know that tapentadol may make you drowsy. Do not drive a car, operate machinery, or participate in any other possibly dangerous activities until you know how this medication affects you.
• you should know that tapentadol may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that tapentadol may cause constipation. Talk to your doctor about changing your diet or using other medications to prevent or treat constipation while you are taking tapentadol.

Tapentadol 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 tapentadol, 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 tapentadol with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Samidorphan
• Selegiline
• Tranylcypromine

Using tapentadol 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Citalopram
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cocaine
• Codeine
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Escitalopram
• Esketamine
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluoxetine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lorazepam
• Lorcaserin
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Metoclopramide
• Midazolam
• Milnacipran
• Mirtazapine
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naratriptan
• Nefazodone
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Ozanimod
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Periciazine
• Perphenazine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Remifentanil
• Remimazolam
• Remoxipride
• Rizatriptan
• Scopolamine
• Secobarbital
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Other interactions

Using tapentadol 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 tapentadol, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Tapentadol uses

Tapentadol tablets are used to treat moderate to severe acute pain (pain that begins suddenly, has a specific cause, and is expected to go away when the cause of the pain is healed). Tapentadol extended-release tablets are used to treat severe neuropathic pain (pain caused by nerve damage) in people who have diabetes. Tapentadol extended-release tablets are only used to treat people who are expected to need medication around-the-clock to relieve pain that cannot be controlled by the use of other pain medications.

Tapentadol dosage

The dose of tapentadol 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 tapentadol. 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 oral dosage form (extended-release tablets)

• For severe pain:
  • Patients switching from Nucynta® to Nucynta® ER:
    • Adults—The tablet is given every 12 hours. The total amount of milligrams (mg) per day is the same as the total amount of regular tapentadol that is taken per day. The total amount per day will be divided and given as 2 divided doses during the day. However, the dose is usually not more than 500 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • Patients who are not taking narcotic medicines:
    • Adults—At first, 50 milligrams (mg) 2 times a day (every 12 hours). Your doctor may adjust your dose as needed. However, the dose is usually not more than 500 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • Patients switching from other narcotic medicines:
    • Adults—The tablet is given every 12 hours. The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. The total amount per day will be divided and given as 2 divided doses during the day. However, the dose is usually not more than 500 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For nerve pain caused by diabetes:
  • Adults—At first, 50 milligrams (mg) 2 times a day (every 12 hours). Your doctor may adjust your dose as needed. However, the dose is usually not more than 500 mg per day.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (immediate-release tablets)

• For moderate to severe pain:
  • Adults—At first, 50 to 100 milligrams (mg) every 4 to 6 hours. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (solution)

• For moderate to severe pain:
  • Adults—At first, 2.5 milliliters (mL) (50 milligrams [mg]), 3.75 mL (75 mg), or 5 mL (100 mg) every 4 to 6 hours. On the first day of dosing, the second dose may be given as soon as 1 hour after the first dose, if pain is not relieved with the first dose. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

• For moderate to severe pain:
  • Adults—At first, 50 to 100 milligrams (mg) every 4 to 6 hours. On the first day of dosing, the second dose may be given as soon as 1 hour after the first dose, if pain is not relieved with the first dose. Your doctor may adjust your dose as needed.
  • Children—Use and dose must be determined by your doctor.

Missed dose

If you are taking tapentadol tablets, your doctor will probably tell you to take the medication as needed. If your doctor has told you to take the tablets regularly, take the missed dose as soon as you remember it. Do not take a double dose to make up for a missed one.

If you are taking tapentadol extended-release capsules, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Tapentadol side effects

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

• headache
• heartburn
• stomach pain
• dry mouth
• excessive tiredness
• anxiety
• drowsiness
• difficulty falling asleep or staying asleep
• abnormal dreams
• irritability
• sudden feeling of warmth

Some side effects can be serious. If you experience any of these symptoms or those listed in the SPECIAL PRECAUTIONS or IMPORTANT WARNING sections, call your doctor immediately or get emergency medical treatment:

• seizures
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• rash
• itching
• hives
• swelling of the eyes, face, lips, tongue, or throat
• hoarseness
• difficulty breathing or swallowing
• chest pain
• feeling lightheaded when you change positions
• feeling faint
• loss of consciousness
• feeling overheated
• heavy sweating

Tapentadol may cause other side effects. Call your doctor if you have any unusual problems while you are taking tapentadol.

Tramadol

Tramadol is a pain medicine similar to an opioid and is classified as a synthetic opioid. Tramadol is used to treat moderate to severe pain in adults. The extended-release form of tramadol is for around-the-clock treatment of pain. This form of tramadol is not for use on an as-needed basis for pain. Tramadol is available only under a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

Tramadol comes as a tablet, a solution (liquid), an extended-release (long-acting) tablet, and an extended-release (long-acting) capsule to take by mouth. The regular tablet and solution are taken usually with or without food every 4 to 6 hours as needed. The extended-release tablet and extended-release capsule should be taken once a day. Take the extended-release tablet and the extended-release capsule at about the same time of day every day. If you are taking the extended-release capsule, you may take it with or without food. If you are taking the extended-release tablet, you should either always take it with food or always take it without food. Take tramadol exactly as directed. Do not take more medication as a single dose or take more doses per day than prescribed by your doctor. Taking more tramadol than prescribed by your doctor or in a way that is not recommended may cause serious side effects or death.

Your doctor may start you on a low dose of tramadol and gradually increase the amount of medication you take, not more often than every 3 days if you are taking the solution, regular tablets or orally disintegrating tablets or every 5 days if you are taking the extended-release tablets or extended-release capsules.

If you are taking the solution, use an oral syringe or measuring spoon or cup to measure the correct amount of liquid needed for each dose. Do not use a regular household spoon to measure your dose. Ask your doctor or pharmacist if you need help getting or using a measuring device,

Do not stop taking tramadol without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking tramadol, you may experience withdrawal symptoms such as nervousness; panic; sweating; difficulty falling asleep or staying asleep; runny nose, sneezing, or cough; pain; hair standing on end; chills; nausea; uncontrollable shaking of a part of your body; diarrhea; or rarely, hallucinations (seeing things or hearing voices that do not exist).

Tramadol special precautions

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

• Adrenal problems or
• Alcohol abuse, history of or
• Brain tumor or
• Depression, history of or
• Diabetes or
• Drug abuse or dependence, history of or
• Gallstones or
• Head injury or
• Hormonal problems or
• Increased pressure in the head or
• Infections of the central nervous system (CNS) or
• Lung or breathing problems (eg, COPD, cor pulmonale, hypercapnia, hypoxia, sleep apnea) or
• Mental illness (eg, suicidal ideation), history of or
• Phenylketone allergy, history of or
• Seizures or epilepsy, history of or
• Stomach problems, severe—Use with caution. May increase risk for more serious side effects.
• Kidney disease or
• Liver disease (including cirrhosis)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• Lung or breathing problems (eg, asthma, hypercapnia, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus) or
• Surgery (eg, nasopharyngeal tonsils, tonsils)—Should not be used in patients with these conditions.
• Phenylketonuria (PKU)—The orally disintegrating tablet contains phenylalanine, which can make this condition worse.

Before taking tramadol:

• tell your doctor and pharmacist if you are allergic to tramadol, other opiate pain medications, any other medications, or any of the ingredients in tramadol products. Ask your pharmacist for a list of the ingredients.
• tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Your doctor will probably tell you not to take tramadol if you are taking one or more of these medications, or have taken them within the past 2 weeks.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven); bupropion (Aplenzin, Wellbutrin, Zyban); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); digoxin (Lanoxin); diuretics (‘water pills’); lithium (Lithobid); certain medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); promethazine; 5-HT3 receptor antagonists such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem, Selfemra), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq, Khedezla), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); trazodone (Oleptro); and tricyclic antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with tramadol, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, a blockage or narrowing of your stomach or intestines, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take tramadol if you have any of these conditions.
• tell your doctor if you have or have ever had seizures; an infection in your brain or spine; difficulty urinating; thoughts about harming or killing yourself or planning or trying to do so; or kidney or liver disease.
• tell your doctor if you are breastfeeding. You should not breastfeed while taking tramadol. Tramadol can cause shallow breathing, difficulty or noisy breathing, confusion, more than usual sleepiness, trouble breastfeeding, or limpness in breastfed infants.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking tramadol.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tramadol.
• you should know that this medication may make you drowsy and may affect your coordination. Do not drive a car or operate machinery until you know how this medication affects you.
• you should know that tramadol may cause dizziness, lightheadedness, and fainting when you get up from a lying position. To avoid this, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• 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 orally disintegrating tablets contain aspartame, a source of phenylalanine.
• you should know that tramadol may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.

Tramadol 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 tramadol, 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 tramadol with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Samidorphan
• Selegiline
• Tranylcypromine

Using tramadol 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.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Aprepitant
• Aripiprazole
• Armodafinil
• Asenapine
• Atazanavir
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Bromperidol
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Cinacalcet
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclosporine
• Darunavir
• Delavirdine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Dothiepin
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Enzalutamide
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Gabapentin
• Gabapentin Enacarbil
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirabegron
• Mirtazapine
• Mitotane
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naratriptan
• Nefazodone
• Nelfinavir
• Nevirapine
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Peginterferon Alfa-2b
• Pentazocine
• Pentobarbital
• Perampanel
• Periciazine
• Perphenazine
• Phenobarbital
• Phenytoin
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Prochlorperazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinidine
• Quinine
• Ramelteon
• Ranitidine
• Ranolazine
• Remifentanil
• Remimazolam
• Remoxipride
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rizatriptan
• Rolapitant
• Saquinavir
• Scopolamine
• Secobarbital
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John’s Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Terbinafine
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using tramadol 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.

• Warfarin

Other interactions

Using tramadol 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 tramadol, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol
• Grapefruit Juice

Tramadol uses

Tramadol is used to relieve moderate to moderately severe pain, including pain after surgery. Tramadol extended-release tablets and capsules are only used by people who are expected to need medication to relieve pain around-the-clock.

Tramadol dosage

The dose of tramadol 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 tramadol. 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 chronic pain

• For oral dosage form (extended-release capsules)
  • Adults—At first, 100 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 300 mg per day.
  • Children 12 years of age and older—Use and dose must be determined by your doctor.
  • Children younger than 12 years of age—Should not be used in these patients.
• For oral dosage form (extended-release tablets)
  • Adults—At first, 100 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 300 mg per day.
  • Children—Use and dose must be determined by your doctor.

For moderate to severe pain

• For oral dosage form (disintegrating tablets)
  • Adults and children 16 years of age and older—At first, 50 to 100 milligrams (mg) every 4 to 6 hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
  • Children younger than 16 years of age—Use and dose must be determined by your doctor.
• For oral dosage form (solution)
  • Adults—At first, 25 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
  • Children younger than 12 years of age—Should not be used in these patients.
• For oral dosage form (tablets)
  • Adults—At first, 25 milligrams (mg) per day, taken every morning. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 400 mg per day.
  • Older adults over 75 years of age—At first, 25 mg per day, taken every morning. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 300 mg per day.
  • Children 12 years of age and older—Use and dose must be determined by your doctor.
  • Children younger than 12 years of age—Should not be used in these patients.

Missed dose

If your doctor has told you to take tramadol 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.

Tramadol side effects

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

• sleepiness
• headache
• nervousness
• uncontrollable shaking of a part of the body
• muscle tightness
• changes in mood
• heartburn or indigestion
• dry mouth

Some side effects can be serious. If you experience any of these symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• hives
• rash
• blisters
• hoarseness
• difficulty swallowing or breathing
• swelling of the eyes, face, throat, tongue, lips, hands, feet, ankles, or lower legs
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination,
• nausea, vomiting, or diarrhea
• nausea, vomiting, loss of appetite, weakness, or dizziness
• changes in heartbeat
• nausea, vomiting, headache, confusion, loss of energy, drowsiness, fatigue, restlessness, irritability, muscle weakness, spasms or cramps
• hunger, headache, sweating, shaking of a part of your body that you cannot control, irritability, or difficulty concentrating
• loss of consciousness
• seizures. Seizures have been reported in patients taking tramadol. Your risk of seizures is higher if you are taking higher doses than recommended. Seizure risk is also higher in those with a seizure disorder or those taking certain antidepressants or opioid medications.

Tramadol may cause other side effects. Tell your doctor if you have any unusual problems while you are taking tramadol.

1. Vold, J. H., Skurtveit, S., Aas, C., Johansson, K. A., & Fadnes, L. T. (2020). Too much or too little opioids to patients receiving opioid agonist therapy in Norway (2013-2017): a prospective cohort study. BMC health services research, 20(1), 668. https://doi.org/10.1186/s12913-020-05504-y
2. Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I., Degenhardt, L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017). Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ (Clinical research ed.), 357, j1550. https://doi.org/10.1136/bmj.j1550
3. Opioid Overdose Crisis. https://www.drugabuse.gov/drug-topics/opioids/opioid-overdose-crisis
4. Florence CS, Zhou C, Luo F, Xu L. The Economic Burden of Prescription Opioid Overdose, Abuse, and Dependence in the United States, 2013. Med Care. 2016;54(10):901-906. doi:10.1097/MLR.0000000000000625
5. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Opioids. [Updated 2020 Nov 24]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547864
6. Morone NE, Weiner DK. Pain as the fifth vital sign: exposing the vital need for pain education. Clin Ther. 2013;35(11):1728-1732. doi:10.1016/j.clinthera.2013.10.001
7. CDC/NCHS, National Vital Statistics System, Mortality. CDC WONDER, Atlanta, GA: US Department of Health and Human Services, CDC; 2019. https://wonder.cdc.gov
8. Center for Behavioral Health Statistics and Quality (CBHSQ). 2017 National Survey on Drug Use and Health: Detailed Tables. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2018
9. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-576. doi:10.1097/01.j.pain.0000460357.01998.f1
10. Carlson RG, Nahhas RW, Martins SS, Daniulaityte R. Predictors of transition to heroin use among initially non-opioid dependent illicit pharmaceutical opioid users: A natural history study. Drug Alcohol Depend. 2016;160:127-134. doi:10.1016/j.drugalcdep.2015.12.026
11. Muhuri PK, Gfroerer JC, Davies MC. Associations of Nonmedical Pain Reliever Use and Initiation of Heroin Use in the United States. CBHSQ Data Rev. August 2013
12. Dydyk AM, Jain NK, Gupta M. Opioid Use Disorder. [Updated 2021 Jul 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553166
13. Vallersnes OM, Jacobsen D, Ekeberg Ø, Brekke M. Mortality, morbidity and follow-up after acute poisoning by substances of abuse: A prospective observational cohort study. Scand J Public Health. 2019 Jun;47(4):452-461. doi: 10.1177/1403494818779955
14. Chang, H. Y., Kharrazi, H., Bodycombe, D., Weiner, J. P., & Alexander, G. C. (2018). Healthcare costs and utilization associated with high-risk prescription opioid use: a retrospective cohort study. BMC medicine, 16(1), 69. https://doi.org/10.1186/s12916-018-1058-y
15. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. Arlington: American Psychiatric Association, 2013.
16. Buprenorphine Therapy for Opioid Use Disorder. Am Fam Physician. 2018 Mar 1;97(5):313-320. https://www.aafp.org/afp/2018/0301/p313.html
17. Welsh C, Valadez-Meltzer A. Buprenorphine: a (relatively) new treatment for opioid dependence. Psychiatry (Edgmont). 2005;2(12):29–39.
18. Amass L, Kamien JB, Mikulich SK. Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans. Drug Alcohol Depend. 2001;61(2):173–181.
19. Mendelson J, Upton RA, Everhart ET, Jacob P III, Jones RT. Bioavailability of sublingual buprenorphine. J Clin Pharmacol. 1997;37(1):31–37.
20. Chavoustie S, Frost M, Snyder O, et al. Buprenorphine implants in medical treatment of opioid addiction. Expert Rev Clin Pharmacol. 2017;10(8):799–807.
21. Beilin Y, Bodian CA, Weiser J, Hossain S, Arnold I, Feierman DE, Martin G, Holzman I. Effect of labor epidural analgesia with and without fentanyl on infant breast-feeding: a prospective, randomized, double-blind study. Anesthesiology. 2005 Dec;103(6):1211-7. doi: 10.1097/00000542-200512000-00016
22. Lee AI, McCarthy RJ, Toledo P, Jones MJ, White N, Wong CA. Epidural Labor Analgesia-Fentanyl Dose and Breastfeeding Success: A Randomized Clinical Trial. Anesthesiology. 2017 Oct;127(4):614-624. doi: 10.1097/ALN.0000000000001793
23. Brimdyr K, Cadwell K, Widström AM, Svensson K, Neumann M, Hart EA, Harrington S, Phillips R. The Association Between Common Labor Drugs and Suckling When Skin-to-Skin During the First Hour After Birth. Birth. 2015 Dec;42(4):319-28. doi: 10.1111/birt.12186
24. Moore A, el-Bahrawy A, Hatzakorzian R, Li-Pi-Shan W. Maternal Epidural Fentanyl Administered for Labor Analgesia Is Found in Neonatal Urine 24 Hours After Birth. Breastfeed Med. 2016 Jan-Feb;11(1):40-1. doi: 10.1089/bfm.2015.0173
25. French CA, Cong X, Chung KS. Labor Epidural Analgesia and Breastfeeding: A Systematic Review. J Hum Lact. 2016 Aug;32(3):507-20. doi: 10.1177/0890334415623779
26. ASGE Standard of Practice Committee, Shergill AK, Ben-Menachem T, Chandrasekhara V, Chathadi K, Decker GA, Evans JA, Early DS, Fanelli RD, Fisher DA, Foley KQ, Fukami N, Hwang JH, Jain R, Jue TL, Khan KM, Lightdale J, Pasha SF, Sharaf RN, Dominitz JA, Cash BD. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc. 2012 Jul;76(1):18-24. doi: 10.1016/j.gie.2012.02.029. Epub 2012 May 12. Erratum in: Gastrointest Endosc. 2013 May;77(5):833.
27. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Fentanyl. [Updated 2021 Feb 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501222
28. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Fentanyl. [Updated 2019 Apr 25]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548026