AUDIENCE: Internal Medicine, Pharmacy, Psychiatry
ISSUE: Based on an FDA review of a large clinical trial that FDA required the drug companies to conduct, FDA determined the risk of serious side effects on mood, behavior, or thinking with the stop-smoking medicines varenicline (ChantixÂ®) and bupropion (ZybanÂ®) is lower than previously suspected. The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past. However, most people who had these side effects did not have serious consequences such as hospitalization. The results of the trial confirm that the benefits of stopping smoking outweigh the risks of these medicines. See the Drug Safety Communication, available at: http://bit.ly/2j0SGSB, for a data summary.
As a result of the large clinical trial review, FDA is removing the Boxed Warning, FDA's most prominent warning, for serious mental health side effects from the varenicline drug label. The language describing the serious mental health side effects seen in patients quitting smoking will also be removed from the Boxed Warning in the bupropion label. FDA is also updating the existing warning section in both labels that describes the side effects on mood, behavior, or thinking to include the results from the clinical trial. This decision is consistent with the recommendations of external experts at a September 2016 FDA Advisory Committee meeting. The patient Medication Guide that explains the risks associated with the use of the medicines will continue to be provided with every patient prescription; however, the risk evaluation and mitigation strategy (REMS) that formally required the Medication Guide will be removed.
BACKGROUND: FDA review of the clinical trial results also confirmed that varenicline, bupropion, and nicotine replacement patches were all more effective for helping people quit smoking than was an inactive treatment called a placebo. These medicines were found to better help people quit smoking regardless of whether or not they had a history of mental illness.
RECOMMENDATION: Health care professionals should counsel patients about the benefits of stopping smoking and how they can get help to quit, and discuss the benefits and risks of using medicines to help them quit smoking.
Patients should stop taking varenicline or bupropion and call their health care professionals right away if they notice any side effects on mood, behavior, or thinking. Patients should also talk to their health care professionals for help and information about stopping smoking, including about whether stop-smoking medicines may help or if they have any questions or concerns about taking a medicine (See Related Information for more quit smoking resources).
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
For people taking bupropion (Zyban) to stop smoking:
Some people have reported symptoms such as changes in behavior, hostility, agitation, depressed mood, and suicidal thoughts (thinking about harming or killing oneself or planning or trying to do so) while taking bupropion to stop smoking. The role of bupropion in causing these mood changes is unclear since people who quit smoking with or without medication may experience changes in their mental health due to nicotine withdrawal. However, some of these symptoms occurred in people who were taking bupropion and continued to smoke. Some people had these symptoms when they began taking bupropion, and others developed them after several weeks of treatment or after stopping bupropion. These symptoms have occurred in people without a history of mental illness and have worsened in people who already had a mental illness. Tell your doctor if you have or have ever had depression, bipolar disorder (mood that changes from depressed to abnormally excited), schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions), or other mental illnesses.
If you experience any of the following symptoms, stop taking bupropion (Zyban) and call your doctor immediately: suicidal thoughts or actions; new or worsening depression, anxiety, or panic attacks; agitation; restlessness; angry or violent behavior; acting dangerously; mania (frenzied, abnormally excited or irritated mood); abnormal thoughts or sensations; hallucinations (seeing things or hearing voices that do not exist); feeling that people are against you; feeling confused; or any other sudden or unusual changes in behavior. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own. Your doctor will monitor you closely until your symptoms get better.
For people taking bupropion (Wellbutrin) for depression:
A small number of children, teenagers, and young adults (up to 24 years of age) who took antidepressants ('mood elevators') such as bupropion during clinical studies became suicidal (thinking about harming or killing oneself or planning or trying to do so). Children, teenagers, and young adults who take antidepressants to treat depression or other mental illnesses may be more likely to become suicidal than children, teenagers, and young adults who do not take antidepressants to treat these conditions. This risk should be considered and compared with the potential benefit in the treatment of depression, in deciding whether a child or teenager should take an antidepressant. Children younger than 18 years of age should not normally take bupropion, but in some cases, a doctor may decide that bupropion is the best medication to treat a child's condition.
No matter what your age, before you take an antidepressant, you, your parent, or your caregiver should talk to your doctor about the risks and benefits of treating your condition with an antidepressant or with other treatments. You should also talk about the risks and benefits of not treating your condition. You should know that having depression or another mental illness greatly increases the risk that you will become suicidal, especially at the beginning of your treatment or any time that your dose is increased or decreased. This risk is higher if you or anyone in your family has or has ever had bipolar disorder or mania or has thought about or attempted suicide. Talk to your doctor about your condition, symptoms, and personal and family medical history. You and your doctor will decide what type of treatment is right for you.
You should know that your mental health may change in unexpected ways when you take bupropion or other antidepressants even if you are an adult over age 24 or if you do not have a mental illness and you are taking bupropion to treat a different type of condition. You may become suicidal, especially at the beginning of your treatment and any time that your dose is increased or decreased. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: new or worsening depression; thinking about harming or killing yourself, or planning or trying to do so; extreme worry; agitation; panic attacks; difficulty falling asleep or staying asleep; aggressive behavior; irritability; acting without thinking; severe restlessness; and frenzied abnormal excitement. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.
For all patients taking bupropion:
Your health care provider will want to see you often while you are taking bupropion, especially at the beginning of your treatment. Be sure to keep all appointments or office visits with your doctor.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with bupropion and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You also can visit the Food and Drug Administration (FDA) website: http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks and benefits of taking bupropion.
Why is this medication prescribed?
Bupropion (Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL) is used to treat depression. Bupropion (Aplenzin, Wellbutrin XL) is also used to treat seasonal affective disorder (SAD; episodes of depression that occur at the same time each year [usually in the fall and winter but rarely may occur in the spring or summer months]). Bupropion (Zyban) is used to help people stop smoking. Bupropion is in a class of medications called antidepressants. It works by increasing certain types of activity in the brain.
How should this medicine be used?
Bupropion comes as a tablet and a sustained-release or extended-release (long-acting) tablet to take by mouth. The regular tablet (Wellbutrin) is usually taken three times a day, with doses at least 6 hours apart, or four times a day, with doses at least 4 hours apart. The sustained-release tablet (Wellbutrin SR, Zyban) is usually taken twice a day, with doses at least 8 hours apart. The extended-release tablet (Aplenzin, Wellbutrin XL) is usually taken once daily in the morning; doses of the extended-release tablet should be taken at least 24 hours apart. When bupropion is used to treat seasonal affective disorder, it is usually taken once a day in the morning beginning in the early fall, continuing through the winter, and stopping in the early spring. Sometimes a lower dose of bupropion is taken for 2 weeks before the medication is stopped. Take bupropion with food if the medication upsets your stomach. If you have trouble falling asleep or staying asleep, do not take bupropion too close to bedtime. Take bupropion 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 bupropion exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the sustained-release and extended-release tablets whole; do not split, chew, or crush them.
Your doctor will probably start you on a low dose of bupropion and gradually increase your dose.
It may take 4 weeks or longer before you feel the full benefit of bupropion. Continue to take bupropion even if you feel well. Do not stop taking bupropion without talking to your doctor. Your doctor may decrease your dose gradually.
Other uses for this medicine
Bupropion is also sometimes used to treat episodes of depression in patients with bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) and to treat attention deficit hyperactivity disorder (ADHD; more difficulty focusing, controlling actions, and remaining still or quiet than other people who are the same age). Talk to your doctor about the possible risks of using this medication for your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking bupropion,
- tell your doctor and pharmacist if you are allergic to bupropion, any other medications, or any of the ingredients in bupropion tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take bupropion.
- do not take more than one product containing bupropion at a time. You could receive too much medication and experience severe side effects.
- 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: amantadine (Symmetrel); beta blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); cimetidine (Tagamet); clopidogrel (Plavix); cyclophosphamide (Cytoxan, Neosar); efavirenz (Sustiva, in Atripla); insulin or oral medications for diabetes; medications for irregular heartbeat such as flecainide (Tambocor) and propafenone (Rythmol); medications for mental illness such as haloperidol (Haldol), risperidone (Risperdal), and thioridazine (Mellaril); medications for seizures such as carbamazepine (Tegretol), phenobarbital (Luminal, Solfoton), and phenytoin (Dilantin); levodopa (Sinemet, Larodopa); lopinavir and ritonavir (Kaletra); nelfinavir (Viracept); nicotine patch; oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); orphenadrine (Norflex); other antidepressants such as citalopram (Celexa), desipramine (Norpramin), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), paroxetine (Paxil) and sertraline (Zoloft); ritonavir (Norvir); sedatives; sleeping pills; tamoxifen (Nolvadex, Soltamox); theophylline (Theobid, Theo-Dur, others); thiotepa; and ticlopidine (Ticlid). 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 seizures, anorexia nervosa (an eating disorder) or bulimia (an eating disorder). Also tell your doctor if you drink large amounts of alcohol but expect to suddenly stop drinking or you take sedatives but expect to suddenly stop taking them. Your doctor will probably tell you not to take bupropion.
- tell your doctor if you drink large amounts of alcohol, use street drugs, or overuse prescription medications and if you have ever had a heart attack; a head injury; a tumor in your brain or spine; high blood pressure; diabetes; or liver, kidney, or heart disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking bupropion, call your doctor.
- you should know that bupropion may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- talk to your doctor about the safe use of alcoholic beverages while you are taking bupropion. Alcohol can make the side effects from bupropion worse.
- you should know that bupropion may cause an increase in your blood pressure. Your doctor may check your blood pressure before starting treatment and regularly while you are taking this medication, especially if you also are using nicotine replacement therapy.
- you should know that bupropion may cause angle-closure glaucoma (a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision). Talk to your doctor about having an eye examination before you start taking this medication. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, call your doctor or get emergency medical treatment right away.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Always allow the full scheduled amount of time to pass between doses of bupropion. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Bupropion may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty falling asleep or staying asleep
- dry mouth
- stomach pain
- uncontrollable shaking of a part of the body
- loss of appetite
- weight loss
- excessive sweating
- ringing in the ears
- changes in your sense of taste
- frequent urination
- sore throat
Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, call your doctor immediately or get emergency medical treatment:
- hallucinating (seeing things or hearing voices that do not exist)
- irrational fears
- muscle or joint pain
- rapid, pounding, or irregular heartbeat
If you experience any of the following symptoms, stop taking bupropion and call your doctor immediately or get emergency medical treatment:
- rash or blisters
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- difficulty breathing or swallowing
- chest pain
Bupropion may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include the following:
- hallucinating (seeing things or hearing voices that do not exist)
- loss of consciousness
- rapid or pounding heartbeat
What other information should I know?
Keep all appointments with your doctor.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking bupropion.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
If you are taking the extended-release tablet, you may notice something that looks like a tablet in your stool. This is just the empty tablet shell and does not mean that you did not get your complete dose of medication.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
¶ This branded product is no longer on the market. Generic alternatives may be available.