Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with WELLBUTRIN and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for WELLBUTRIN. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document. Additional important information concerning WELLBUTRIN is provided in a tear-off leaflet entitled "Patient Information" at the end of this labeling.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking WELLBUTRIN.
Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers
should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patientís prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patientís presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.
Patients should be made aware that WELLBUTRIN contains the same active ingredient found in ZYBAN, used as an aid to smoking cessation, and that WELLBUTRIN should not be used in combination with ZYBAN or any other medications that contain bupropion hydrochloride.
Patients should be instructed to take WELLBUTRIN in equally divided doses 3 or 4 times a day to minimize the risk of seizure.
Patients should be told that WELLBUTRIN should be discontinued and not restarted if they experience a seizure while on treatment.
Patients should be told that any CNS-active drug like WELLBUTRIN may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Consequently, until they are reasonably certain that WELLBUTRIN does not adversely affect their performance, they should refrain from driving an automobile or operating complex, hazardous machinery.
Patients should be told that the excessive use or abrupt discontinuation of alcohol or sedatives (including benzodiazepines) may alter the seizure threshold. Some patients have reported lower alcohol tolerance during treatment with WELLBUTRIN. Patients should be advised that the consumption of alcohol should be minimized or avoided.
Patients should be advised to inform their physicians if they are taking or plan to take any prescription or over-the-counter drugs. Concern is warranted because WELLBUTRIN and other drugs may affect each otherís metabolism.
Patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy.
WELLBUTRINÒ (WELL byu-trin)
(bupropion hydrochloride) Tablets
Read this information completely before you start taking WELLBUTRIN. Read the information each time you get more medicine. There may be something new. This leaflet provides a summary about WELLBUTRIN. It does not include everything there is to know about your medicine. This information should not take the place of discussions with your doctor aboutyour medical condition or WELLBUTRIN.
What is the most important information I should know about WELLBUTRIN?
· At a dose of up to 450 mg each day, there is a chance that approximately 4 out of every 1,000 people taking bupropion hydrochloride, the active ingredient in WELLBUTRIN, will have a seizure. The chance of seizures further increases with doses above 450 mg a day. Seizures are also called convulsions. They can cause you to fall with uncontrolled shaking.
·You may have an increased risk of seizures while taking WELLBUTRIN if you have certain medical problems. Be sure to tell your doctor about all of your medical problems.
·You may have an increased risk of seizures while taking WELLBUTRIN if you take certain medicines. Be sure to tell your doctor about all the medicines you take, including non-prescription medicines and herbal or natural supplements.
For more information, see the section "Who should not take WELLBUTRIN?"
If you have a seizure while taking WELLBUTRIN, stop taking the tablets and call your doctor right away. Do not take WELLBUTRIN again if you have a seizure.
What is important information I should know and share with my family about taking antidepressants?
Patients and their families should watch out for worsening depression or thoughts of suicide. Also watch out for sudden or severe changes in feelings such as feeling anxious, agitated, panicky, irritable, hostile, aggressive, impulsive, severely restless, overly excited and hyperactive, not being able to sleep or other unusual changes in behavior. If this happens, especially at the beginning of antidepressant treatment or after a change in dose, call your doctor. A patient Medication Guide will be provided to you with each prescription of WELLBUTRIN that is entitled "About Using Antidepressants in Children and Teenagers." WELLBUTRIN is not approved for the use in children and teenagers.
What is WELLBUTRIN?
WELLBUTRIN is a prescription medicine used to treat depression. WELLBUTRIN is thought to treat depression by correcting an imbalance of certain chemicals in your brain.
Who should not take WELLBUTRIN?
Do not take WELLBUTRIN if you
· have or have ever had a seizure disorder such as epilepsy.
· are taking ZYBAN (used to help people stop smoking) or any other medicines that contain bupropion hydrochloride, the active ingredient in WELLBUTRIN.
· are abruptly discontinuing use of alcohol or sedatives (including benzodiazepines).
· have taken within the last 14 days one of the medicines for depression known as a monoamine oxidase inhibitor (MAOI), such as NARDILÒ* (phenelzine sulfate), PARNATEÒ (tranylcypromine sulfate), or MARPLANÒ* (isocarboxazid).
· have or have ever had an eating disorder such as anorexia nervosa or bulimia.
· are allergic to the active ingredient, bupropion, or to any of the inactive ingredients. Your doctor and pharmacist have a list of the inactive ingredients.
What should I tell my doctor before using WELLBUTRIN?
·Tell your doctor about your medical conditions. Tell your doctor if you
· are pregnant or plan to become pregnant. It is not known if WELLBUTRIN can harm the unborn baby.
· are breast feeding. WELLBUTRIN passes through your milk. It is not known whether WELLBUTRIN in breast milk can harm the baby.
· have liver or kidney problems.
· have an eating disorder, such as anorexia nervosa or bulimia.
· have had a head injury.
· have had a seizure.
· have a tumor in your nervous system.
· recently had a heart attack, have heart problems, or have high blood pressure.
· are a diabetic taking insulin or other medicines to control your blood sugar.
· are a heavy drinker of alcoholic beverages.
· use tranquilizers or sedatives frequently.
·Tell your doctor about all the medicines you take, including non-prescription medicines and herbal or natural remedies. Some may increase your chance of getting seizures or other side effects if you take WELLBUTRIN.
How should I take WELLBUTRIN?
· Take WELLBUTRIN at the same time each day exactly as prescribed by your doctor. You may take WELLBUTRIN with or without food.
· It may take 4 weeks or more for you to feel that WELLBUTRIN is working. Once you feel better, it is important to keep taking WELLBUTRIN as directed by your doctor.
· Take your doses at least 6 hours apart.
· If you miss a dose, do not take an extra tablet to make up for the dose you forgot. Wait and take your next tablet at the regular time. This is important so you do not increase your chance of having a seizure.
What should I avoid while taking WELLBUTRIN?
· Limit the amount of alcohol you drink while taking WELLBUTRIN. If you usually drink a lot of alcohol, talk with your doctor before suddenly stopping. If you suddenly stop drinking alcohol, you may increase your risk of seizures.
· Do not drive a car or use heavy machinery until you know if WELLBUTRIN affects your ability to perform these tasks.
What are possible side effects of WELLBUTRIN?
·Seizures. Some patients get seizures while taking WELLBUTRIN. If you have a seizure while taking WELLBUTRIN, stop taking the tablets and call your doctor right away.
Do not take WELLBUTRIN again if you have a seizure.
·Hypertension (high blood pressure). Some patients get high blood pressure, sometimes severe, while taking WELLBUTRIN. The chance of high blood pressure may be increased if you also use nicotine replacement therapy (for example a nicotine patch) to help you stop smoking.
Call your doctor right away if you get a rash, itching, hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, swelling of the lips or tongue, or have trouble breathing. These could be signs of a serious allergic reaction.
The most common side effects of WELLBUTRIN are nervousness, constipation, trouble sleeping, dry mouth, headache, nausea, vomiting, and shakiness (tremor).
If you have nausea, you may want to take your medicine with food. If you have difficulty sleeping, avoid taking your medicine too close to bedtime.
These are not all the side effects of WELLBUTRIN. For a complete list, ask your doctor or pharmacist. Tell your doctor right away about any side effects that bother you. Do not change your dose or stop taking WELLBUTRIN without talking with your doctor first.
General Information about WELLBUTRIN.
· Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use WELLBUTRIN for a condition for which it was not prescribed. Do not give WELLBUTRIN to other people, even if they have the same symptoms you have. It may harm them. Keep WELLBUTRIN out of the reach of children.
· Store WELLBUTRIN at room temperature, out of direct sunlight. Keep WELLBUTRIN in a tightly closed container.
This leaflet summarizes the most important information about WELLBUTRIN. For more information, talk to your doctor or pharmacist. They can give you information about WELLBUTRIN that is written for health professionals.
*The following are registered trademarks of their respective manufacturers:
NardilÒ /Warner Lambert Company; MarplanÒ /Oxford Pharmaceutical Services, Inc.Manufactured by DSM Pharmaceuticals,
Inc.Greenville, NC 27834 for GlaxoSmithKline Research Triangle Park, NC 27709Ó2005,
GlaxoSmithKline. All rights reserved. January 2005 RL-2165
WELLBUTRINÒ (WELL byu-trin)
(bupropion hydrochloride) Tablets
About Using Antidepressants in Children and Teenagers
What is the most important information I should know if my child is being prescribed an antidepressant?
Parents or guardians need to think about 4 important things when their child is prescribed an antidepressant:
1. There is a risk of suicidal thoughts or actions
2. How to try to prevent suicidal thoughts or actions in your child
3. You should watch for certain signs if your child is taking an antidepressant
4. There are benefits and risks when using antidepressants
1. There is a Risk of Suicidal Thoughts or Actions
Children and teenagers sometimes think about suicide, and many report trying to kill themselves.
Antidepressants increase suicidal thoughts and actions in some children and teenagers. But suicidal thoughts and actions can also be caused by depression, a serious medical condition that is commonly treated with antidepressants. Thinking about killing yourself or trying to kill yourself is called suicidality or being suicidal.
A large study combined the results of 24 different studies of children and teenagers with depression or other illnesses. In these studies, patients took either a placebo (sugar pill) or an antidepressant for 1 to 4 months. No one committed suicide in these studies, but some patients became suicidal. On sugar pills, 2 out of every 100 became suicidal. On the antidepressants, 4 out of every 100 patients became suicidal.
For some children and teenagers, the risks of suicidal actions may be especially high. These include patients with
· Bipolar illness (sometimes called manic-depressive illness)
· A family history of bipolar illness
· A personal or family history of attempting suicide
If any of these are present, make sure you tell your healthcare provider before your child takes an antidepressant.
2. How to Try to Prevent Suicidal Thoughts and Actions
To try to prevent suicidal thoughts and actions in your child, pay close attention to changes in her or his moods or actions, especially if the changes occur suddenly. Other important people in your childís life can help by paying attention as well (e.g., your child, brothers and sisters, teachers, and other important people). The changes to look out for are listed in Section 3, on what to watch for.
Whenever an antidepressant is started or its dose is changed, pay close attention to your child. After starting an antidepressant, your child should generally see his or her healthcare provider:
· Once a week for the first 4 weeks
· Every 2 weeks for the next 4 weeks
· After taking the antidepressant for 12 weeks
· After 12 weeks, follow your healthcare providerís advice about how often to come back
· More often if problems or questions arise
You should call your childís healthcare provider between visits if needed.
3. You Should Watch For Certain Signs if Your Child is Taking an Antidepressant
Contact your childís healthcare provider right away if your child exhibits any of the following signs for the first time, or they seem worse, or worry you, your child, or your childís teacher:
· Thoughts about suicide or dying
· Attempts to commit suicide
· New or worse depression
· New or worse anxiety
· Feeling very agitated or restless
· Panic attacks
· Difficulty sleeping (insomnia)
· New or worse irritability
· Acting aggressive, being angry, or violent
· Acting on dangerous impulses
· An extreme increase in activity and talking
· Other unusual changes in behavior or mood
Never let your child stop taking an antidepressant without first talking to his or her healthcare provider. Stopping an antidepressant suddenly can cause other symptoms.
4. There are Benefits and Risks When Using Antidepressants
Antidepressants are used to treat depression and other illnesses. Depression and other illnesses can lead to suicide. In some children and teenagers, treatment with an antidepressant increases suicidal thinking or actions. It is important to discuss all the risks of treating depression and also the risks of not treating it. You and your child should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.
Other side effects can occur with antidepressants.
Of all antidepressants, only fluoxetine (ProzacÒ )* has been FDA approved to treat pediatric depression.
For obsessive compulsive disorder in children and teenagers, FDA has approved only fluoxetine (Prozac® )*, sertraline (ZoloftÒ )*, fluvoxamine, and clomipramine (Anafranil® )*.
Your healthcare provider may suggest other antidepressants based on the past experience of your child or other family members.
Is this all I need to know if my child is being prescribed an antidepressant?
No. This is a warning about the risk of suicidality. Other side effects can occur with antidepressants. Be sure to ask your healthcare provider to explain all the side effects of the particular drug he or she is prescribing. Also ask about drugs to avoid when taking an antidepressant. Ask your healthcare provider or pharmacist where to find more information.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.January 2005 MG-WT:1Manufactured by DSM Pharmaceuticals, Inc.Greenville, NC 27834 for Glaxo Smith Kline Research Triangle Park, NC 27709Ó2005, Glaxo Smith Kline. All rights reserved. January 2005 RL-2165
Few systemic data have been collected on the metabolism of WELLBUTRIN following concomitant administration with other drugs or, alternatively, the effect of concomitant administration of WELLBUTRIN on the metabolism of other drugs.
Because bupropion is extensively metabolized, the coadministration of other drugs may affect its clinical activity. In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by the CYP2B6 isoenzyme. Therefore, the potential exists for a drug interaction between WELLBUTRIN and drugs that affect the CYP2B6 isoenzyme (e.g., orphenadrine and cyclophosphamide). The threohydrobupropion metabolite of bupropion does not appear to be produced by the cytochrome P450 isoenzymes. The effects of concomitant administration of cimetidine on the pharmacokinetics of bupropion and its active metabolites were studied in 24 healthy young male volunteers. Following oral administration of two 150-mg sustained-release tablets with and without 800 mg of cimetidine, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.
While not systematically studied, certain drugs may induce the metabolism of bupropion (e.g., carbamazepine, phenobarbital, phenytoin).
Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in humans. In one study, following chronic administration of bupropion, 100 mg 3 times daily to 8 healthy male volunteers for 14 days, there was no evidence of induction of its own metabolism. Nevertheless, there may be the potential for clinically important alterations of blood levels of coadministered drugs.
Drugs Metabolized by Cytochrome P450IID6 (CYP2D6): Many drugs, including most antidepressants (SSRIs, many tricyclics), beta-blockers, antiarrhythmics, and antipsychotics are metabolized by the CYP2D6 isoenzyme. Although bupropion is not metabolized by this isoenzyme, bupropion and hydroxybupropion are inhibitors of the CYP2D6 isoenzyme in vitro. In a study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of the CYP2D6 isoenzyme, daily doses of bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine increased the Cmax, AUC, and t1/2 of desipramine by an average of approximately 2-, 5- and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Concomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.
Therefore, co-administration of bupropion with drugs that are metabolized by CYP2D6 isoenzyme including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide), should be approached with caution and should be initiated at the lower end of the dose range of the concomitant medication. If bupropion is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need to decrease the dose of the original medication should be considered, particularly for those concomitant medications with a narrow therapeutic index.
MAO Inhibitors: Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine .
Levodopa and Amantadine: Limited clinical data suggest a higher incidence of adverse experiences in patients receiving bupropion concurrently with either levodopa or amantadine. Administration of WELLBUTRIN Tablets to patients receiving either levodopa or amantadine concurrently should be undertaken with caution, using small initial doses and small gradual dose increases.
Drugs that Lower Seizure Threshold: Concurrent administration of WELLBUTRIN and agents (e.g., antipsychotics, other antidepressants, theophylline, systemic steroids, etc.) that lower seizure threshold should be undertaken only with extreme caution. Low initial dosing and small gradual dose increases should be employed.
Nicotine Transdermal System: .
Alcohol: In post-marketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with WELLBUTRIN. The consumption of alcohol during treatment with WELLBUTRIN should be minimized or avoided (also see CONTRAINDICATIONS).
WELLBUTRIN is contraindicated in patients with a seizure disorder.
WELLBUTRIN is contraindicated in patients treated with ZYBANÒ (bupropion hydrochloride) Sustained-Release Tablets, or any other medications that contain bupropion because the incidence of seizure is dose dependent.
WELLBUTRIN is also contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa because of a higher incidence of seizures noted in such patients treated with WELLBUTRIN.
WELLBUTRIN is contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).
The concurrent administration of WELLBUTRIN and a monoamine oxidase (MAO) inhibitor is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with WELLBUTRIN.
WELLBUTRIN is contraindicated in patients who have shown an allergic response to bupropion or the other ingredients that make up WELLBUTRIN Tablets.