BUDEPRION (bupropion hydrochloride 150 mg) Dailymed

Precautions

General

Agitation and Insomnia

Patients in placebo-controlled trials with bupropion hydrochloride extended-release tablets (SR) experienced agitation, anxiety, and insomnia as shown in Table 2.

Table 2. Incidence of Agitation, Anxiety, and Insomnia in Placebo-Controlled Trials

Adverse Event Term	Bupropion Hydrochloride Extended-Release Tablets (SR)300 mg/day(n=376)	Bupropion Hydrochloride Extended-Release Tablets (SR)400 mg/day (n=114)	Placebo(n=385)
Agitation	3%	9%	2%
Anxiety	5%	6%	3%
Insomnia	11%	16%	6%

In clinical studies, these symptoms were sometimes of sufficient magnitude to require treatment with sedative/hypnotic drugs.

Symptoms were sufficiently severe to require discontinuation of treatment in 1% and 2.6% of patients treated with 300 and 400 mg/day, respectively, of bupropion hydrochloride extended-release tablets (SR) and 0.8% of patients treated with placebo.

Psychosis, Confusion, and Other Neuropsychiatric Phenomena

Depressed patients treated with an immediate-release formulation of bupropion or with bupropion hydrochloride extended-release tablets (SR) have been reported to show a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. In some cases, these symptoms abated upon dose reduction and/or withdrawal of treatment.

Activation of Psychosis and/or Mania

Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible patients. Bupropion hydrochloride extended-release tablets (SR) are expected to pose similar risks.

Altered Appetite and Weight

In placebo-controlled studies, patients experienced weight gain or weight loss as shown in Table 3.

Table 3. Incidence of Weight Gain and Weight Loss in Placebo-Controlled Trials

Weight Change	Bupropion Hydrochloride Extended-Release Tablets (SR)300 mg/day(n=339)	Bupropion Hydrochloride Extended-Release Tablets (SR)400 mg/day(n=112)	Placebo(n=347)
Gained > 5 lbs	3%	2%	4%
Lost > 5 lbs	14%	19%	6%

In studies conducted with the immediate-release formulation of bupropion, 35% of patients receiving tricyclic antidepressants gained weight, compared to 9% of patients treated with the immediate-release formulation of bupropion. If weight loss is a major presenting sign of a patient's depressive illness, the anorectic and/or weight-reducing potential of bupropion hydrochloride extended-release tablets (SR) should be considered.

Allergic Reactions

Anaphylactoid/anaphylactic reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. In addition, there have been rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion. A patient should stop taking bupropion hydrochloride extended-release tablets (SR) and consult a doctor if experiencing allergic or anaphylactoid/anaphylactic reactions (e.g., skin rash, pruritus, hives, chest pain, edema, and shortness of breath) during treatment.

Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity have been reported in association with bupropion. These symptoms may resemble serum sickness.

The 100 mg strength of this product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin sensitivity.

Cardiovascular Effects

In clinical practice, hypertension, in some cases severe, requiring acute treatment, has been reported in patients receiving bupropion alone and in combination with nicotine replacement therapy. These events have been observed in both patients with and without evidence of preexisting hypertension.

Data from a comparative study of the sustained-release formulation of bupropion (ZYBAN^® Sustained-Release Tablets), nicotine transdermal system (NTS), the combination of sustained-release bupropion plus NTS, and placebo as an aid to smoking cessation suggest a higher incidence of treatment-emergent hypertension in patients treated with the combination of sustained-release bupropion and NTS. In this study, 6.1% of patients treated with the combination of sustained-release bupropion and NTS had treatment-emergent hypertension compared to 2.5%, 1.6%, and 3.1% of patients treated with sustained-release bupropion, NTS, and placebo, respectively. The majority of these patients had evidence of preexisting hypertension. Three patients (1.2%) treated with the combination of ZYBAN^® and NTS and 1 patient (0.4%) treated with NTS had study medication discontinued due to hypertension compared to none of the patients treated with ZYBAN^® or placebo. Monitoring of blood pressure is recommended in patients who receive the combination of bupropion and nicotine replacement.

There is no clinical experience establishing the safety of bupropion hydrochloride extended-release tablets (SR) in patients with a recent history of myocardial infarction or unstable heart disease. Therefore, care should be exercised if it is used in these groups. Bupropion was well tolerated in depressed patients who had previously developed orthostatic hypotension while receiving tricyclic antidepressants, and was also generally well tolerated in a group of 36 depressed inpatients with stable congestive heart failure (CHF). However, bupropion was associated with a rise in supine blood pressure in the study of patients with CHF, resulting in discontinuation of treatment in 2 patients for exacerbation of baseline hypertension.

Hepatic Impairment

Bupropion hydrochloride extended-release tablets (SR) should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients, a reduced frequency and/or dose is required. Bupropion hydrochloride extended-release tablets (SR) should be used with caution in patients with hepatic impairment (including mild-to-moderate hepatic cirrhosis) and reduced frequency and/or dose should be considered in patients with mild-to-moderate hepatic cirrhosis.

All patients with hepatic impairment should be closely monitored for possible adverse effects that could indicate high drug and metabolite levels (see CLINICAL PHARMACOLOGY, WARNINGS, and DOSAGE AND ADMINISTRATION).

Renal Impairment

There is limited information on the pharmacokinetics of bupropion in patients with renal impairment. An inter-study comparison between normal subjects and patients with end-stage renal failure demonstrated that the parent drug C_max and AUC values were comparable in the 2 groups, whereas the hydroxybupropion and threohydrobupropion metabolites had a 2.3- and 2.8-fold increase, respectively, in AUC for patients with end-stage renal failure. A second study, comparing normal subjects and patients with moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min) showed that exposure to a single 150-mg dose of sustained-release bupropion was approximately 2-fold higher in patients with impaired renal function while levels of the hydroxybupropion and threo/erythrohydrobupropion (combined) metabolites were similar in the 2 groups. Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. Bupropion hydrochloride extended-release tablets (SR) should be used with caution in patients with renal impairment and a reduced frequency and/or dose should be considered as bupropion and the metabolites of bupropion may accumulate in such patients to a greater extent than usual. The patient should be closely monitored for possible adverse effects that could indicate high drug or metabolite levels.

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with bupropion hydrochloride extended-release tablets (SR) and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions," "Quitting Smoking, Quit-Smoking Medication, Changes in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions," and "What Other Important Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (SR)?" is available for bupropion hydrochloride extended-release tablets (SR). 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.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking bupropion hydrochloride extended-release tablets (SR).

Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders

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 look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's 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.

Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment

Although bupropion hydrochloride extended-release tablets (SR) are not indicated for smoking cessation treatment, it contains the same active ingredient as ZYBAN^® which is approved for this use. Patients should be informed that quitting smoking, with or without ZYBAN^®, may be associated with nicotine withdrawal symptoms (including depression or agitation), or exacerbation of pre-existing psychiatric illness. Furthermore, some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide when attempting to quit smoking while taking ZYBAN^®. If patients develop agitation, hostility, depressed mood, or changes in thinking or behavior that are not typical for them, or if patients develop suicidal ideation or behavior, they should be urged to report these symptoms to their healthcare provider immediately.

Bupropion-Containing Products

Patients should be made aware that bupropion hydrochloride extended-release tablets (SR) contain the same active ingredient found in ZYBAN^®, used as an aid to smoking cessation treatment, and that bupropion hydrochloride extended-release tablets (SR) should not be used in combination with ZYBAN^® or any other medications that contain bupropion hydrochloride (such as WELLBUTRIN^®, the immediate-release formulation and WELLBUTRIN XL^®, the extended-release formulation).

As dose is increased during initial titration to doses above 150 mg/day, patients should be instructed to take bupropion hydrochloride extended-release tablets (SR) in 2 divided doses, preferably with at least 8 hours between successive doses, to minimize the risk of seizures.

Patients should be told that bupropion hydrochloride extended-release tablets (SR) should be discontinued and not restarted if they experience a seizure while on treatment.

Patients should be told that any CNS-active drug like bupropion hydrochloride extended-release tablets (SR) may impair their ability to perform tasks requiring judgment or motor and cognitive skills. Consequently, until they are reasonably certain that bupropion hydrochloride extended-release tablets (SR) do 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 bupropion hydrochloride extended-release tablets (SR). 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 bupropion hydrochloride extended-release tablets (SR) and other drugs may affect each other's metabolism.

Patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy.

Patients should be advised to swallow bupropion hydrochloride extended-release tablets (SR) whole so that the release rate is not altered. Do not chew, divide, or crush tablets, as this may lead to an increased risk of adverse effects, including seizures.

Laboratory Tests

There are no specific laboratory tests recommended.

Drug Interactions

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 bupropion hydrochloride extended-release tablets (SR) and drugs that are substrates of or inhibitors/inducers of the CYP2B6 isoenzyme (e.g., orphenadrine, thiotepa, cyclophosphamide, ticlopidine, and clopidogrel). In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, and fluvoxamine as well as nelfinavir inhibit the hydroxylation of bupropion. No clinical studies have been performed to evaluate this finding. 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 bupropion hydrochloride extended-release tablets (SR) 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 C_max, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.

In a series of studies in healthy volunteers, ritonavir (100 mg twice daily or 600 mg twice daily) or ritonavir 100 mg plus lopinavir 400 mg (KALETRA^®) twice daily reduced the exposure of bupropion and its major metabolites in a dose dependent manner by approximately 20% to 80%. Similarly, efavirenz 600 mg once daily for 2 weeks reduced the exposure of bupropion by approximately 55%. This effect of ritonavir, KALETRA^®, and efavirenz is thought to be due to the induction of bupropion metabolism. Patients receiving any of these drugs with bupropion may need increased doses of bupropion, but the maximum recommended dose of bupropion should not be exceeded (see CLINICAL PHARMACOLOGY: Metabolism).

While not systematically studied, certain drugs may induce the metabolism of bupropion (e.g., carbamazepine, phenobarbital, phenytoin).

Multiple oral doses of bupropion had no statistically significant effects on the single-dose pharmacokinetics of lamotrigine in 12 healthy volunteers.

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 CYP2D6 isoenzyme in vitro. In a study of 15 male subjects (aged 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 C_max, AUC, and t_1/2 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, coadministration 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.

Drugs which require metabolic activation by CYP2D6 in order to be effective (e.g., tamoxifen) theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion.

Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion increased the C_max and AUC of citalopram by 30% and 40%, respectively. Citalopram did not affect the pharmacokinetics of bupropion and its 3 metabolites.

MAO Inhibitors

Concomitant use of MAOIs and bupropion is contraindicated. Bupropion inhibits the reuptake of dopamine and norepinephrine and can increase risk of hypertensive reactions when used concomitantly with drugs that also inhibit the reuptake of dopamine or norepinephrine, including MAOIs. In addition, MAOIs decrease the metabolism of dopamine and norepinephrine. These effects can increase dopaminergic and noradrenergic activity. Studies in animals demonstrate that the acute toxicity of bupropion is enhanced by the MAO inhibitor phenelzine (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

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 bupropion hydrochloride extended-release tablets (SR) to patients receiving either levodopa or amantadine concurrently should be undertaken with caution, using small initial doses and gradual dose increases.

Drugs That Lower Seizure Threshold

Concurrent administration of bupropion hydrochloride extended-release tablets (SR) and agents (e.g., antipsychotics, other antidepressants, theophylline, systemic steroids, etc.) that lower seizure threshold should be undertaken only with extreme caution (see WARNINGS). Low initial dosing and gradual dose increases should be employed.

Nicotine Transdermal System

(see PRECAUTIONS: Cardiovascular Effects).

Alcohol

In postmarketing experience, there have been rare reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who were drinking alcohol during treatment with bupropion hydrochloride extended-release tablets (SR). The consumption of alcohol during treatment with bupropion hydrochloride extended-release tablets (SR) should be minimized or avoided (also see CONTRAINDICATIONS).

Drug-Laboratory Test Interactions

False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. This is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime carcinogenicity studies were performed in rats and mice at doses up to 300 and 150 mg/kg/day, respectively. These doses are approximately 7 and 2 times the maximum recommended human dose (MRHD), respectively, on a mg/m² basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day (approximately 2 to 7 times the MRHD on a mg/m² basis); lower doses were not tested. The question of whether or not such lesions may be precursors of neoplasms of the liver is currently unresolved. Similar liver lesions were not seen in the mouse study, and no increase in malignant tumors of the liver and other organs was seen in either study.

Bupropion produced a positive response (2 to 3 times control mutation rate) in 2 of 5 strains in the Ames bacterial mutagenicity test and an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies.

A fertility study in rats at doses up to 300 mg/kg/day revealed no evidence of impaired fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

In studies conducted in rats and rabbits, bupropion was administered orally at doses up to 450 and 150 mg/kg/day, respectively (approximately 11 and 7 times the MRHD, respectively, on a mg/m² basis), during the period of organogenesis. No clear evidence of teratogenic activity was found in either species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the MRHD on a mg/m² basis) and greater. Decreased fetal weights were seen at 50 mg/kg and greater.

When rats were administered bupropion at oral doses of up to 300 mg/kg/day (approximately 7 times the MRHD on a mg/m² basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse effects on offspring development.

One study has been conducted in pregnant women. This retrospective, managed-care database study assessed the risk of congenital malformations overall and cardiovascular malformations specifically, following exposure to bupropion in the first trimester compared to the risk of these malformations following exposure to other antidepressants in the first trimester and bupropion outside of the first trimester. This study included 7,005 infants with antidepressant exposure during pregnancy, 1,213 of whom were exposed to bupropion in the first trimester. The study showed no greater risk for congenital malformations overall or cardiovascular malformations specifically, following first trimester bupropion exposure compared to exposure to all other antidepressants in the first trimester, or bupropion outside of the first trimester. The results of this study have not been corroborated. Bupropion hydrochloride extended-release tablets (SR) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of bupropion hydrochloride extended-release tablets (SR) on labor and delivery in humans is unknown.

Nursing Mothers

Like many other drugs, bupropion and its metabolites are secreted in human milk. Because of the potential for serious adverse reactions in nursing infants from bupropion hydrochloride extended-release tablets (SR), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS: Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders). Anyone considering the use of bupropion hydrochloride extended-release tablets (SR) in a child or adolescent must balance the potential risks with the clinical need.

Geriatric Use

Of the approximately 6,000 patients who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation studies), 275 were 65 and over and 47 were 75 and over. In addition, several hundred patients 65 and over participated in clinical trials using the immediate-release formulation of bupropion (depression studies). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that of younger subjects; however, another pharmacokinetic study, single and multiple dose, has suggested that the elderly are at increased risk for accumulation of bupropion and its metabolites (see CLINICAL PHARMACOLOGY).

Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of toxic reaction to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS: Renal Impairment and DOSAGE AND ADMINISTRATION).

Adverse Reactions

(See also WARNINGS and PRECAUTIONS.)

The information included under the Incidence in Controlled Trials subsection of ADVERSE REACTIONS is based primarily on data from controlled clinical trials with bupropion hydrochloride extended-release tablets (SR). Information on additional adverse events associated with the sustained-release formulation of bupropion in smoking cessation trials, as well as the immediate-release formulation of bupropion, is included in a separate section (see Other Events Observed During the Clinical Development and Postmarketing Experience of Bupropion).

Incidence in Controlled Trials With Bupropion Hydrochloride Extended-Release Tablets (SR)

Adverse Events Associated With Discontinuation of Treatment Among Patients Treated With Bupropion Hydrochloride Extended-Release Tablets (SR)

In placebo-controlled clinical trials, 9% and 11% of patients treated with 300 and 400 mg/day, respectively, of bupropion hydrochloride extended-release tablets (SR) and 4% of patients treated with placebo discontinued treatment due to adverse events. The specific adverse events in these trials that led to discontinuation in at least 1% of patients treated with either 300 or 400 mg/day of bupropion hydrochloride extended-release tablets (SR) and at a rate at least twice the placebo rate are uled in Table 4.

Table 4. Treatment Discontinuations Due to Adverse Events in Placebo-Controlled Trials

Adverse Event Term	Bupropion HCl ERTablets (SR)300 mg/day(n=376)	Bupropion HCl ERTablets (SR)400 mg/day(n=114)	Placebo(n=385)
Rash	2.4%	0.9%	0.0%
Nausea	0.8%	1.8%	0.3%
Agitation	0.3%	1.8%	0.3%
Migraine	0.0%	1.8%	0.3%

Adverse Events Occurring at an Incidence of 1% or More Among Patients Treated With Bupropion Hydrochloride Extended-Release Tablets (SR)

Table 5 enumerates treatment-emergent adverse events that occurred among patients treated with 300 and 400 mg/day of bupropion hydrochloride extended-release tablets (SR) and with placebo in placebo-controlled trials. Events that occurred in either the 300- or 400-mg/day group at an incidence of 1% or more and were more frequent than in the placebo group are included. Reported adverse events were classified using a COSTART-based Dictionary.

Accurate estimates of the incidence of adverse events associated with the use of any drug are difficult to obtain. Estimates are influenced by drug dose, detection technique, setting, physician judgments, etc. The figures cited cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. These incidence figures also cannot be compared with those obtained from other clinical studies involving related drug products as each group of drug trials is conducted under a different set of conditions.

Finally, it is important to emphasize that the tabulation does not reflect the relative severity and/or clinical importance of the events. A better perspective on the serious adverse events associated with the use of bupropion hydrochloride extended-release tablets (SR) is provided in the WARNINGS and PRECAUTIONS sections.

Table 5. Treatment-Emergent Adverse Events In Placebo-Controlled TrialsAdverse events that occurred in at least 1% of patients treated with either 300 or 400 mg/day of bupropion hydrochloride extended-release tablets (SR), but equally or more frequently in the placebo group, were: abnormal dreams, accidental injury, acne, appetite increased, back pain, bronchitis, dysmenorrhea, dyspepsia, flatulence, flu syndrome, hypertension, neck pain, respiratory disorder, rhinitis, and tooth disorder.

Body System/Adverse Event	Bupropion HCl ER Tablets (SR)300 mg/day(n=376)	Bupropion HCl ER Tablets (SR)400 mg/day(n=114)	Placebo(n = 385)
-- Hyphen denotes adverse events occurring in greater than 0 but less than 0.5% of patients.
Body (General)
  Headache	26%	25%	23%
  Infection	8%	9%	6%
  Abdominal pain	3%	9%	2%
  Asthenia	2%	4%	2%
  Chest pain	3%	4%	1%
  Pain	2%	3%	2%
  Fever	1%	2%	--
Cardiovascular
  Palpitation	2%	6%	2%
  Flushing	1%	4%	--
  Migraine	1%	4%	1%
  Hot flashes	1%	3%	1%
Digestive
  Dry mouth	17%	24%	7%
  Nausea	13%	18%	8%
  Constipation	10%	5%	7%
  Diarrhea	5%	7%	6%
  Anorexia	5%	3%	2%
  Vomiting	4%	2%	2%
  Dysphagia	0%	2%	0%
Musculoskeletal
  Myalgia	2%	6%	3%
  Arthralgia	1%	4%	1%
  Arthritis	0%	2%	0%
  Twitch	1%	2%	--
Nervous system
  Insomnia	11%	16%	6%
  Dizziness	7%	11%	5%
  Agitation	3%	9%	2%
  Anxiety	5%	6%	3%
  Tremor	6%	3%	1%
  Nervousness	5%	3%	3%
  Somnolence	2%	3%	2%
  Irritability	3%	2%	2%
  Memory decreased	--	3%	1%
  Paresthesia	1%	2%	1%
  Central nervous system stimulation	2%	1%	1%
Respiratory
  Pharyngitis	3%	11%	2%
  Sinusitis	3%	1%	2%
  Increased cough	1%	2%	1%
Skin
  Sweating	6%	5%	2%
  Rash	5%	4%	1%
  Pruritus	2%	4%	2%
  Urticaria	2%	1%	0%
Special senses
  Tinnitus	6%	6%	2%
  Taste perversion	2%	4%	--
  Blurred vision or diplopia	3%	2%	2%
Urogenital
  Urinary frequency	2%	5%	2%
  Urinary urgency	--	2%	0%
  Vaginal hemorrhage Incidence based on the number of female patients.	0%	2%	--
  Urinary tract infection	1%	0%	--

Incidence of Commonly Observed Adverse Events in Controlled Clinical Trials

Adverse events from Table 5 occurring in at least 5% of patients treated with bupropion hydrochloride extended-release tablets (SR) and at a rate at least twice the placebo rate are uled below for the 300- and 400-mg/day dose groups.

Bupropion Hydrochloride Extended-Release Tablets (SR) 300 mg/day: Anorexia, dry mouth, rash, sweating, tinnitus, and tremor.

Bupropion Hydrochloride Extended-Release Tablets (SR) 400 mg/day: Abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency.

Other Events Observed During the Clinical Development and Postmarketing Experience of Bupropion

In addition to the adverse events noted above, the following events have been reported in clinical trials and postmarketing experience with the sustained-release formulation of bupropion in depressed patients and in nondepressed smokers, as well as in clinical trials and postmarketing clinical experience with the immediate-release formulation of bupropion.

Adverse events for which frequencies are provided below occurred in clinical trials with the sustained-release formulation of bupropion. The frequencies represent the proportion of patients who experienced a treatment-emergent adverse event on at least one occasion in placebo-controlled studies for depression (n=987) or smoking cessation (n=1,013), or patients who experienced an adverse event requiring discontinuation of treatment in an open-label surveillance study with bupropion hydrochloride extended-release tablets (SR) (n=3,100). All treatment-emergent adverse events are included except those uled in Tables 2 through 5, those events uled in other safety-related sections, those adverse events subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, those events not reasonably associated with the use of the drug, and those events that were not serious and occurred in fewer than 2 patients. Events of major clinical importance are described in the WARNINGS and PRECAUTIONS sections of the labeling.

Events are further categorized by body system and uled in order of decreasing frequency according to the following definitions of frequency: Frequent adverse events are defined as those occurring in at least 1/100 patients. Infrequent adverse events are those occurring in 1/100 to 1/1,000 patients, while rare events are those occurring in less than 1/1,000 patients.

Adverse events for which frequencies are not provided occurred in clinical trials or postmarketing experience with bupropion. Only those adverse events not previously uled for sustained-release bupropion are included. The extent to which these events may be associated with bupropion hydrochloride extended-release tablets (SR) is unknown.

Body (General)

Infrequent were chills, facial edema, musculoskeletal chest pain, and photosensitivity. Rare was malaise. Also observed were arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness (see PRECAUTIONS).

Cardiovascular

Infrequent were postural hypotension, stroke, tachycardia, and vasodilation. Rare was syncope. Also observed were complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe, see PRECAUTIONS), myocardial infarction, phlebitis, and pulmonary embolism.

Digestive

Infrequent were abnormal liver function, bruxism, gastric reflux, gingivitis, glossitis, increased salivation, jaundice, mouth ulcers, stomatitis, and thirst. Rare was edema of tongue. Also observed were colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, liver damage, pancreatitis, and stomach ulcer.

Endocrine

Also observed were hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone.

Hemic and Lymphatic

Infrequent was ecchymosis. Also observed were anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.

Metabolic and Nutritional

Infrequent were edema and peripheral edema. Also observed was glycosuria.

Musculoskeletal

Infrequent were leg cramps. Also observed were muscle rigidity/fever/rhabdomyolysis and muscle weakness.

Nervous System

Infrequent were abnormal coordination, decreased libido, depersonalization, dysphoria, emotional lability, hostility, hyperkinesia, hypertonia, hypesthesia, suicidal ideation, and vertigo. Rare were amnesia, ataxia, derealization, and hypomania. Also observed were abnormal electroencephalogram (EEG), akinesia, aggression, aphasia, coma, completed suicide, delirium, delusions, dysarthria, dyskinesia, dystonia, euphoria, extrapyramidal syndrome, hallucinations, hypokinesia, increased libido, manic reaction, neuralgia, neuropathy, paranoid ideation, restlessness, suicide attempt, and unmasking tardive dyskinesia.

Respiratory

Rare was bronchospasm. Also observed was pneumonia.

Skin

Rare was maculopapular rash. Also observed were alopecia, angioedema, exfoliative dermatitis, and hirsutism.

Special Senses

Infrequent were accommodation abnormality and dry eye. Also observed were deafness, diplopia, increased intraocular pressure, and mydriasis.

Urogenital

Infrequent were impotence, polyuria, and prostate disorder. Also observed were abnormal ejaculation, cystitis, dyspareunia, dysuria, gynecomastia, menopause, painful erection, salpingitis, urinary incontinence, urinary retention, and vaginitis.

Drug Abuse And Dependence

Controlled Substance Class

Bupropion is not a controlled substance.

Humans

Controlled clinical studies of bupropion (immediate-release formulation) conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients showed some increase in motor activity and agitation/exclient.

In a population of individuals experienced with drugs of abuse, a single dose of 400 mg of bupropion produced mild amphetamine-like activity as compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI. These scales measure general feelings of euphoria and drug desirability.

Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be especially reinforcing to amphetamine or stimulant abusers. However, higher doses that could not be tested because of the risk of seizure might be modestly attractive to those who abuse stimulant drugs.

Animals

Studies in rodents and primates have shown that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms. In primate models to assess the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

Overdosage

Human Overdose Experience

Overdoses of up to 30 g or more of bupropion have been reported. Seizure was reported in approximately one-third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, sinus tachycardia, and ECG changes such as conduction disturbances (including QRS prolongation) or arrhythmias. Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.

Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

Overdosage Management

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. EEG monitoring is also recommended for the first 48 hours post-ingestion. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended.

Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the management of bupropion overdoses. No specific antidotes for bupropion are known.

Due to the dose-related risk of seizures with bupropion hydrochloride extended-release tablets (SR), hospitalization following suspected overdose should be considered. Based on studies in animals, it is recommended that seizures be treated with intravenous benzodiazepine administration and other supportive measures, as appropriate.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are uled in the Physicians' Desk Reference (PDR).

Dosage And Administration

General Dosing Considerations

It is particularly important to administer bupropion hydrochloride extended-release tablets (SR) in a manner most likely to minimize the risk of seizure (see WARNINGS). Gradual escalation in dosage is also important if agitation, motor restlessness, and insomnia, often seen during the initial days of treatment, are to be minimized. If necessary, these effects may be managed by temporary reduction of dose or the short-term administration of an intermediate to long-acting sedative hypnotic. A sedative hypnotic usually is not required beyond the first week of treatment. Insomnia may also be minimized by avoiding bedtime doses. If distressing, untoward effects supervene, dose escalation should be stopped. Bupropion hydrochloride extended-release tablets (SR) should be swallowed whole and not crushed, divided, or chewed, as this may lead to an increased risk of adverse effects including seizures.

Initial Treatment

The usual adult target dose for bupropion hydrochloride extended-release tablets (SR) is 300 mg/day, given as 150 mg twice daily. Dosing with bupropion hydrochloride extended-release tablets (SR) should begin at 150 mg/day given as a single daily dose in the morning. If the 150-mg initial dose is adequately tolerated, an increase to the 300-mg/day target dose, given as 150 mg twice daily, may be made as early as day 4 of dosing. There should be an interval of at least 8 hours between successive doses.

Increasing the Dosage Above 300 mg/day

As with other antidepressants, the full antidepressant effect of bupropion hydrochloride extended-release tablets (SR) may not be evident until 4 weeks of treatment or longer. An increase in dosage to the maximum of 400 mg/day, given as 200 mg twice daily, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg/day.

Maintenance Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In a study in which patients with major depressive disorder, recurrent type, who had responded during 8 weeks of acute treatment with bupropion hydrochloride extended-release tablets (SR) were assigned randomly to placebo or to the same dose of bupropion hydrochloride extended-release tablets (SR) (150 mg twice daily) during 44 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated (see CLINICAL TRIALS under CLINICAL PHARMACOLOGY. Based on these limited data, it is unknown whether or not the dose of bupropion hydrochloride extended-release tablets (SR) needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Dosage Adjustment for Patients with Impaired Hepatic Function

Bupropion hydrochloride extended-release tablets (SR) should be used with extreme caution in patients with severe hepatic cirrhosis. The dose should not exceed 100 mg every day or 150 mg every other day in these patients. Bupropion hydrochloride extended-release tablets (SR) should be used with caution in patients with hepatic impairment (including mild-to-moderate hepatic cirrhosis) and a reduced frequency and/or dose should be considered in patients with mild-to-moderate hepatic cirrhosis (see CLINICAL PHARMACOLOGY, WARNINGS, and PRECAUTIONS).

Dosage Adjustment for Patients with Impaired Renal Function

Bupropion hydrochloride extended-release tablets (SR) should be used with caution in patients with renal impairment and a reduced frequency and/or dose should be considered (see CLINICAL PHARMACOLOGY and PRECAUTIONS).

Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with bupropion hydrochloride extended-release tablets (SR). Conversely, at least 14 days should be allowed after stopping bupropion hydrochloride extended-release tablets (SR) before starting an MAOI antidepressant (see CONTRAINDICATIONS and DRUG INTERACTIONS).

Use of Bupropion Hydrochloride Extended-Release Tablets (SR) with Reversible MAOIs such as Linezolid or Methylene Blue

Do not start bupropion hydrochloride extended-release tablets (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered (see CONTRAINDICATIONS and DRUG INTERACTIONS).

In some cases, a patient already receiving therapy with bupropion hydrochloride extended-release tablets (SR) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, bupropion hydrochloride extended-release tablets (SR) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with bupropion hydrochloride extended-release tablets (SR) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with bupropion hydrochloride extended-release tablets (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use (see CONTRAINDICATIONS and DRUG INTERACTIONS).

How Supplied

BUDEPRION SR^®, 100 mg of bupropion hydrochloride, are yellow, round, convex, film-coated tablets, debossed with "G" on one side and "2442" on the other side.

Bottles of 100

NDC 0093-5501-01

BUDEPRION SR^®, 150 mg of bupropion hydrochloride, are light yellow, round, convex, film-coated tablets debossed with "G" on one side and "2444" on the other side.

Bottles of 100

NDC 0093-5502-01

STORAGE AND HANDLING SECTION

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature].

Dispense in tightly closed, light-resistant container (USP).

Manufactured By: IMPAX Laboratories, Inc. Hayward, California 94544 USA

Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960

ZYBAN^®, WELLBUTRIN^® and WELLBUTRIN XL^® are registered trademarks of GlaxoSmithKline.KALETRA^® is a registered trademark of Abbott Laboratories.

514-08Rev. 04/2013

PHARMACIST - DETACH HERE AND GIVE MEDICATION GUIDE TO PATIENT.

Medication Guide

BUDEPRION SR^® (buPROPion HCl Extended-Release Tablets)

Read this Medication Guide carefully before you start using bupropion hydrochloride extended-release tablets (SR) and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about bupropion hydrochloride extended-release tablets (SR), ask your doctor or pharmacist.

IMPORTANT: Be sure to read the three sections of this Medication Guide. The first section is about the risk of suicidal thoughts and actions with antidepressant medicines; the second section is about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions with medicines used to quit smoking; and the third section is entitled "What Other Important Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (SR)?"
Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions

This section of the Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.

Talk to your, or your family member's, healthcare provider about:

• all risks and benefits of treatment with antidepressant medicines
• all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

• 1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
• 2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.
• 3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?
  • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
  • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
  • Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling very agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

• Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
• Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
• Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
• Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a ul of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
• Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child's healthcare provider for more information.

Bupropion hydrochloride extended-release tablets (SR) have not been studied in children under the age of 18 and are not approved for use in children and teenagers.

Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions

This section of the Medication Guide is only about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions with drugs used to quit smoking.

Although bupropion hydrochloride extended-release tablets (SR) are not a treatment for quitting smoking, it contains the same active ingredient (bupropion hydrochloride) as ZYBAN^® which is used to help patients quit smoking.

Some people have had changes in behavior, hostility, agitation, depression, suicidal thoughts or actions while taking bupropion to help them quit smoking. These symptoms can develop during treatment with bupropion or after stopping treatment with bupropion.

If you, your family member, or your caregiver notice agitation, hostility, depression, or changes in thinking or behavior that are not typical for you, or you have any of the following symptoms, stop taking bupropion and call your healthcare provider right away:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• panic attacks
• feeling very agitated or restless
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• abnormal thoughts or sensations
• seeing or hearing things that are not there (hallucinations)
• feeling people are against you (paranoia)
• feeling confused
• other unusual changes in behavior or mood

When you try to quit smoking, with or without bupropion, you may have symptoms that may be due to nicotine withdrawal, including urge to smoke, depressed mood, trouble sleeping, irritability, frustration, anger, feeling anxious, difficulty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain. Some people have even experienced suicidal thoughts when trying to quit smoking without medication. Sometimes quitting smoking can lead to worsening of mental health problems that you already have, such as depression.

Before taking bupropion, tell your healthcare provider if you have ever had depression or other mental illnesses. You should also tell your doctor about any symptoms you had during other times you tried to quit smoking, with or without bupropion.
What Other Important Information Should I Know About Bupropion Hydrochloride Extended-Release Tablets (SR)?

• Seizures: There is a chance of having a seizure (convulsion, fit) with bupropion hydrochloride extended-release tablets (SR), especially in people:
  • with certain medical problems.
  • who take certain medicines.
  The chance of having seizures increases with higher doses of bupropion hydrochloride extended-release tablets (SR). For more information, see the sections "Who should not take bupropion hydrochloride extended-release tablets (SR)?" and "What should I tell my doctor before using bupropion hydrochloride extended-release tablets (SR)?" Tell your doctor about all of your medical conditions and all the medicines you take. Do not take any other medicines while you are using bupropion hydrochloride extended-release tablets (SR) unless your doctor has said it is okay to take them.If you have a seizure while taking bupropion hydrochloride extended-release tablets (SR), stop taking the tablets and call your doctor right away. Do not take bupropion hydrochloride extended-release tablets (SR) again if you have a seizure.
• High blood pressure (hypertension): Some people get high blood pressure, that can be severe, while taking bupropion hydrochloride extended-release tablets (SR). The chance of high blood pressure may be higher if you also use nicotine replacement therapy (such as a nicotine patch) to help you stop smoking.
• Severe allergic reactions: Some people have severe allergic reactions to bupropion hydrochloride extended-release tablets (SR). Stop taking bupropion hydrochloride extended-release tablets (SR) and 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, chest pain, or have trouble breathing. These could be signs of a serious allergic reaction.
• Unusual thoughts or behaviors: Some patients have unusual thoughts or behaviors while taking bupropion hydrochloride extended-release tablets (SR), including delusions (believe you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your doctor.

What are bupropion hydrochloride extended-release tablets (SR)?

Bupropion hydrochloride extended-release tablets (SR) are a prescription medicine used to treat adults with a certain type of depression called major depressive disorder.
Who should not take bupropion hydrochloride extended-release tablets (SR)?

Do not take bupropion hydrochloride extended-release tablets (SR) if you:

• have or had a seizure disorder or epilepsy.
• are taking ZYBAN ^® (used to help people stop smoking) or any other medicines that contain bupropion hydrochloride, such as WELLBUTRIN ^® Tablets or WELLBUTRIN XL ^® Extended-Release Tablets. Bupropion is the same active ingredient that is in bupropion hydrochloride extended-release tablets (SR).
• drink a lot of alcohol and abruptly stop drinking, or use medicines called sedatives (these make you sleepy) or benzodiazepines and you stop using them all of a sudden.
• take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
  • do not take an MAOI within 2 weeks of stopping bupropion hydrochloride extended-release tablets (SR) unless directed to do so by your physician.
  • do not start bupropion hydrochloride extended-release tablets (SR) if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.
• have or had an eating disorder such as anorexia nervosa or bulimia.
• are allergic to the active ingredient in bupropion hydrochloride extended-release tablets (SR), bupropion, or to any of the inactive ingredients. See the end of this leaflet for a complete ul of ingredients in bupropion hydrochloride extended-release tablets (SR).

What should I tell my doctor before using bupropion hydrochloride extended-release tablets (SR)?

Tell your doctor if you have ever had depression, suicidal thoughts or actions, or other mental health problems. See "Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions."

• Tell your doctor about your other medical conditions, including if you:
  • are pregnant or plan to become pregnant. It is not known if bupropion hydrochloride extended-release tablets (SR) can harm your unborn baby.
  • are breastfeeding. Bupropion hydrochloride extended-release tablets (SR) pass through your milk. It is not known if bupropion hydrochloride extended-release tablets (SR) can harm your baby.
  • have liver problems, especially cirrhosis of the liver.
  • have kidney problems.
  • have an eating disorder such as anorexia nervosa or bulimia.
  • have had a head injury.
  • have had a seizure (convulsion, fit).
  • have a tumor in your nervous system (brain or spine).
  • have had a heart attack, heart problems, or high blood pressure.
  • are a diabetic taking insulin or other medicines to control your blood sugar.
  • drink a lot of alcohol.
  • abuse prescription medicines or street drugs.
• Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. Many medicines increase your chances of having seizures or other serious side effects if you take them while you are using bupropion hydrochloride extended-release tablets (SR).

How should I take bupropion hydrochloride extended-release tablets (SR)?

• Take bupropion hydrochloride extended-release tablets (SR) exactly as prescribed by your doctor.
• Do not chew, cut, or crush bupropion hydrochloride extended-release tablets (SR). If you do, the medicine will be released into your body too quickly. If this happens you may be more likely to get side effects including seizures. You must swallow the tablets whole. Tell your doctor if you cannot swallow medicine tablets.
• Take bupropion hydrochloride extended-release tablets (SR) at the same time each day.
• Take your doses of bupropion hydrochloride extended-release tablets (SR) at least 8 hours apart.
• You may take bupropion hydrochloride extended-release tablets (SR) with or without food.
• 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 very important. Too much bupropion hydrochloride extended-release tablets (SR) can increase your chance of having a seizure.
• If you take too much bupropion hydrochloride extended-release tablets (SR), or overdose, call your local emergency room or poison control center right away.
• Do not take any other medicines while using bupropion hydrochloride extended-release tablets (SR) unless your doctor has told you it is okay.
• It may take several weeks for you to feel that bupropion hydrochloride extended-release tablets (SR) are working. Once you feel better, it is important to keep taking bupropion hydrochloride extended-release tablets (SR) exactly as directed by your doctor. Call your doctor if you do not feel bupropion hydrochloride extended-release tablets (SR) are working for you.
• Do not change your dose or stop taking bupropion hydrochloride extended-release tablets (SR) without talking with your doctor first.

What should I avoid while taking bupropion hydrochloride extended-release tablets (SR)?

• Do not drink a lot of alcohol while taking bupropion hydrochloride extended-release tablets (SR). 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 chance of having seizures.
• Do not drive a car or use heavy machinery until you know how bupropion hydrochloride extended-release tablets (SR) affect you. Bupropion hydrochloride extended-release tablets (SR) can impair your ability to perform these tasks.

What are possible side effects of BUDEPRION SR^®?

Bupropion hydrochloride extended-release tablets (SR) can cause serious side effects. Read this entire Medication Guide for more information about these serious side effects.

The most common side effects of bupropion hydrochloride extended-release tablets (SR) are loss of appetite, dry mouth, skin rash, sweating, ringing in the ears, shakiness, stomach pain, agitation, anxiety, dizziness, trouble sleeping, muscle pain, nausea, fast heartbeat, sore throat, and urinating more often.

If you have nausea, take your medicine with food. If you have trouble sleeping, do not take your medicine too close to bedtime.

These are not all the side effects of bupropion hydrochloride extended-release tablets (SR). For a complete ul, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store bupropion hydrochloride extended-release tablets (SR)?

• Store bupropion hydrochloride extended-release tablets (SR) at room temperature. Store out of direct sunlight. Keep bupropion hydrochloride extended-release tablets (SR) in its tightly closed bottle.
• Bupropion hydrochloride extended-release tablets (SR) may have an odor.

General Information about bupropion hydrochloride extended-release tablets (SR).

Medicines are sometimes prescribed for purposes other than those uled in a Medication Guide. Do not use bupropion hydrochloride extended-release tablets (SR) for a condition for which it was not prescribed. Do not give bupropion hydrochloride extended-release tablets (SR) to other people, even if they have the same symptoms you have. It may harm them. Keep bupropion hydrochloride extended-release tablets (SR) out of the reach of children.

If you take a urine drug screening test, bupropion hydrochloride extended-release tablets (SR) may make the test result positive for amphetamines. If you tell the person giving you the drug screening test that you are taking bupropion hydrochloride extended-release tablets (SR), they can do a more specific drug screening test that should not have this problem.

This Medication Guide summarizes important information about bupropion hydrochloride extended-release tablets (SR). For more information, talk with your doctor. You can ask your doctor or pharmacist for information about bupropion hydrochloride extended-release tablets (SR) that is written for health professionals.

What are the ingredients in BUDEPRION SR^®?

Active ingredient: bupropion hydrochloride.

Inactive ingredients: colloidal silicon dioxide, hydroxypropyl cellulose, magnesium stearate and microcrystalline cellulose. The 100 mg tablet also contains FD&C Red No. 40, FD&C Yellow No. 5, hypromellose, iron oxide yellow, macrogol, polydextrose, titanium dioxide and triacetin. The 150 mg tablet also contains hypromellose, iron oxide yellow, macrogol, polydextrose, titanium dioxide and triacetin.

The 100 mg strength of this product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin sensitivity.

Rx only

ZYBAN^®, WELLBUTRIN^®, and WELLBUTRIN XL^® are registered trademarks of GlaxoSmithKline.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured By: IMPAX Laboratories, Inc. Hayward, CA 94544 USA

Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960

514-08Rev. 04/2013

Principal Display Panel - 100 Mg Tablet Bottle Label

NDC 0093-5501-01

BUDEPRION SR ^® (buPROPion HClExtended-release Tablets)

100 mgTwice-A-Day*

WARNING: Do not use in combinationwith Zyban^® or any other medicines thatcontain bupropion hydrochloride.

PHARMACIST: Dispense the accompanyingMedication Guide to each patient.

Rx only

100 TABLETS

TEVA

Principal Display Panel - 150 Mg Tablet Bottle Label

NDC 0093-5502-01

BUDEPRION SR ^® (buPROPion HClExtended-release Tablets)

150 mgTwice-A-Day*

WARNING: Do not use in combinationwith Zyban^® or any other medicines thatcontain bupropion hydrochloride.

PHARMACIST: Dispense the accompanyingMedication Guide to each patient.

Rx only

100 TABLETS

TEVA