Label: BUPROPION HYDROCHLORIDE- bupropion hydrochloride tablet, film coated

  • NDC Code(s): 63629-3233-1, 63629-3233-2, 63629-3233-3, 63629-3233-4, view more
    63629-3233-5, 63629-3233-6
  • Packager: Bryant Ranch Prepack
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated 07/14

If you are a consumer or patient please visit this version.

  • BOXED WARNING(What is this?)

    Suicidality and Antidepressant Drugs

    Use in Treating Psychiatric Disorders: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of bupropion hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Bupropion hydrochloride tablets is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)

    Use in Smoking Cessation Treatment: Bupropion hydrochloride, bupropion hydrochloride, the sustained-release formulation, and bupropion hydrochloride, the extended-release formulation, are not approved for smoking cessation treatment, but bupropion under the name ZYBAN® (bupropion hydrochloride) Sustained-Release Tablets is approved for this use. Serious neuropsychiatric events, including but not limited to depression, suicidal ideation, suicide attempt, and completed suicide have been reported in patients taking bupropion for smoking cessation. Some cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these symptoms have occurred in patients taking bupropion who continued to smoke.

    All patients being treated with bupropion for smoking cessation treatment should be observed for neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, and suicide-related events, including ideation, behavior, and attempted suicide. These symptoms, as well as worsening of pre-existing psychiatric illness and completed suicide have been reported in some patients attempting to quit smoking while taking ZYBAN in the postmarketing experience. When symptoms were reported, most were during treatment with ZYBAN, but some were following discontinuation of treatment with ZYBAN. These events have occurred in patients with and without pre-existing psychiatric disease; some have experienced worsening of their psychiatric illnesses. Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the premarketing studies of ZYBAN.

    Advise patients and caregivers that the patient using bupropion for smoking cessation should stop taking bupropion and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in thinking or behavior that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of ZYBAN was reported, although in some cases the symptoms persisted; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

    The risks of using bupropion for smoking cessation should be weighed against the benefits of its use. bupropion hydrochloride tablets has been demonstrated to increase the likelihood of abstinence from smoking for as long as 6 months compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial. (See WARNINGS: Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment and PRECAUTIONS: Information for Patients.)

    Close
  • DESCRIPTION

    Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride. The molecular weight is 276.2. The molecular formula is C13H18CINO•HCI. Bupropion hydrochloride powder is white, crystalline, and highly soluble in water. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. It has the following structural formula:

    Bupropion Hydrochloride Chemical Structure

    Each bupropion hydrochloride tablet intended for oral administration contains 75 mg or 100 mg bupropion hydrochloride. In addition, each bupropion hydrochloride tablet contains the following inactive ingredients: FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, hydroxypropyl methylcellulose, microcrystalline cellulose, potassium chloride, pregelatinized starch, stearic acid, titanium dioxide, and triethyl citrate.

    Close
  • CLINICAL PHARMACOLOGY

    Pharmacodynamics

    The neurochemical mechanism of the antidepressant effect of bupropion is not known. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the re-uptake of serotonin.

    Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior.

    Bupropion causes convulsions in rodents and dogs at doses approximately tenfold the dose recommended as the human antidepressant dose.

    Pharmacokinetics

    Bupropion is a racemic mixture. The pharmacological activity and pharmacokinetics of the individual enantiomers have not been studied. In humans, following oral administration of bupropion hydrochloride tablets, peak plasma bupropion concentrations are usually achieved within 2 hours, followed by a biphasic decline. The terminal phase has a mean half-life of 14 hours, with a range of 8 to 24 hours. The distribution phase has a mean half-life of 3 to 4 hours. The mean elimination half-life (±SD) of bupropion after chronic dosing is 21 (±9) hours, and steady-state plasma concentrations of bupropion are reached within 8 days. Plasma bupropion concentrations are dose-proportional following single doses of 100 to 250 mg; however, it is not known if the proportionality between dose and plasma level is maintained in chronic use.

    Absorption

    The absolute bioavailability of bupropion hydrochloride tablets in humans has not been determined because an intravenous formulation for human use is not available. However, it appears likely that only a small proportion of any orally administered dose reaches the systemic circulation intact.

    Distribution

    In vitro tests show that bupropion is 84% bound to human plasma protein at concentrations up to 200 mcg/mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that seen with bupropion.

    Metabolism

    Bupropion is extensively metabolized in humans. Three metabolites have been shown to be active: hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group. In vitro findings suggest that cytochrome P450IIB6 (CYP2B6) is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 isoenzymes are not involved in the formation of threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of metachlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized. However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one-half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance because their plasma concentrations are as high or higher than those of bupropion.

    Because bupropion is extensively metabolized, there is the potential for drug-drug interactions, particularly with those agents that are metabolized by or which inhibit/induce the cytochrome P450IIB6 (CYP2B6) isoenzyme, such as ritonavir. In a healthy volunteer study, ritonavir at a dose of 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%.

    In a second healthy volunteer study, ritonavir at a dose of 600 mg twice daily decreased the AUC and the Cmax of bupropion by 66% and 62%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%.

    In another healthy volunteer study, KALETRA®* (lopinavir 400 mg/ritonavir 100 mg twice daily) decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion were decreased by 50% and 31%, respectively (see PRECAUTIONS: Drug Interactions).

    Although bupropion is not metabolized by cytochrome P450IID6 (CYP2D6), there is the potential for drug-drug interactions when bupropion is coadministered with drugs metabolized by this isoenzyme (see PRECAUTIONS: Drug Interactions).

    Following a single dose in humans, peak plasma concentrations of hydroxybupropion occur approximately 3 hours after administration of bupropion hydrochloride tablets. Peak plasma concentrations of hydroxybupropion are approximately 10 times the peak level of the parent drug at steady state. The elimination half-life of hydroxybupropion is approximately 20 (±5) hours, and its AUC at steady state is about 17 times that of bupropion. The times to peak concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that of the hydroxybupropion metabolite. However, their elimination half-lives are longer, 33 (±10) and 37 (±13) hours, respectively, and steady-state AUCs are 1.5 and 7 times that of bupropion, respectively.

    Bupropion and its metabolites exhibit linear kinetics following chronic administration of 300 to 450 mg/day.

    Elimination

    Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. However, the fraction of the oral dose of bupropion hydrochloride tablets excreted unchanged was only 0.5%, a finding consistent with the extensive metabolism of bupropion.

    Populations Subgroups

    Factors or conditions altering metabolic capacity (e.g., liver disease, congestive heart failure [CHF], age, concomitant medications, etc.) or elimination may be expected to influence the degree and extent of accumulation of the active metabolites of bupropion. The elimination of the major metabolites of bupropion may be affected by reduced renal or hepatic function because they are moderately polar compounds and are likely to undergo further metabolism or conjugation in the liver prior to urinary excretion.

    Hepatic

    The effect of hepatic impairment on the pharmacokinetics of bupropion was characterized in 2 single-dose studies, one in patients with alcoholic liver disease and one in patients with mild-to-severe cirrhosis. The first study showed that the half-life of hydroxybupropion was significantly longer in 8 patients with alcoholic liver disease than in 8 healthy volunteers (32 ± 14 hours versus 21 ± 5 hours, respectively). Although not statistically significant, the AUCs for bupropion and hydroxybupropion were more variable and tended to be greater (by 53% to 57%) in volunteers with alcoholic liver disease. The differences in half-life for bupropion and the other metabolites in the 2 patient groups were minimal.

    The second study showed that there were no statistically significant differences in the pharmacokinetics of bupropion and its active metabolites in 9 patients with mild to moderate hepatic cirrhosis compared to 8 healthy volunteers. However, more variability was observed in some of the pharmacokinetic parameters for bupropion (AUC, Cmax, and Tmax) and its active metabolites (t1/2) in patients with mild to moderate hepatic cirrhosis. In addition, in patients with severe hepatic cirrhosis, the bupropion Cmax and AUC were substantially increased (mean difference: by approximately 70% and 3-fold, respectively) and more variable when compared to values in healthy volunteers; the mean bupropion half-life was also longer (29 hours in patients with severe hepatic cirrhosis vs. 19 hours in healthy subjects). For the metabolite hydroxybupropion, the mean Cmax was approximately 69% lower. For the combined amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, the mean Cmax was approximately 31% lower. The mean AUC increased by about 11/2-fold for hydroxybupropion and about 21/2-fold for threo/erythrohydrobupropion. The median Tmax was observed 19 hours later for hydroxybupropion and 31 hours later for threo/erythrohydrobupropion. The mean half-lives for hydroxybupropion and threo/erythrohydrobupropion were increased 5- and 2-fold, respectively, in patients with severe hepatic cirrhosis compared to healthy volunteers (see WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).

    Renal

    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 Cmax 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. The elimination of bupropion and/or the major metabolites of bupropion may be reduced by impaired renal function (see PRECAUTIONS: Renal Impairment).

    Left Ventricular Dysfunction

    During a chronic dosing study in 14 depressed patients with left ventricular dysfunction (history of CHF or an enlarged heart on x-ray), no apparent effect on the pharmacokinetics of bupropion or its metabolites was revealed, compared to healthy volunteers.

    Age

    The effects of age on the pharmacokinetics of bupropion and its metabolites have not been fully characterized, but an exploration of steady-state bupropion concentrations from several depression efficacy studies involving patients dosed in a range of 300 to 750 mg/day, on a 3 times daily schedule, revealed no relationship between age (18 to 83 years) and plasma concentration of bupropion. A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that of younger subjects. These data suggest there is no prominent effect of age on bupropion concentration; 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 PRECAUTIONS: Geriatric Use).

    Gender

    A single-dose study involving 12 healthy male and 12 healthy female volunteers revealed no sex-related differences in the pharmacokinetic parameters of bupropion.

    Smokers

    The effects of cigarette smoking on the pharmacokinetics of bupropion were studied in 34 healthy male and female volunteers; 17 were chronic cigarette smokers and 17 were nonsmokers. Following oral administration of a single 150 mg dose of bupropion, there were no statistically significant differences in Cmax, half-life, Tmax, AUC or clearance of bupropion or its active metabolites between smokers and nonsmokers.

    Close
  • INDICATIONS AND USAGE

    Bupropion hydrochloride tablets are indicated for the treatment of major depressive disorder. A physician considering bupropion hydrochloride tablets for the management of a patient’s first episode of depression should be aware that the drug may cause generalized seizures in a dose-dependent manner with an approximate incidence of 0.4% (4/1,000). This incidence of seizures may exceed that of other marketed antidepressants by as much as 4-fold. This relative risk is only an approximate estimate because no direct comparative studies have been conducted (see WARNINGS).

    The efficacy of bupropion hydrochloride tablets has been established in 3 placebo-controlled trials, including 2 of approximately 3 weeks’ duration in depressed inpatients and one of approximately 6 weeks’ duration in depressed outpatients. The depressive disorder of the patients studied corresponds most closely to the Major Depression category of the APA Diagnostic and Statistical Manual III.

    Major Depression implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigability, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and suicidal ideation or attempts.

    Effectiveness of bupropion hydrochloride tablets in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use bupropion hydrochloride tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

    Close
  • CONTRAINDICATIONS

    Bupropion hydrochloride tablets are contraindicated in patients with a seizure disorder.

    Bupropion hydrochloride tablets are contraindicated in patients treated with ZYBAN (bupropion hydrochloride) Sustained-Release Tablets; Wellbutrin SR (bupropion hydrochloride), the sustained-release formulation; Wellbutrin XL (bupropion hydrochloride), the extended-release formulation; or any other medications that contain bupropion because the incidence of seizure is dose dependent.

    Bupropion hydrochloride tablets are 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 bupropion hydrochloride tablets.

    Bupropion hydrochloride tablets are contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).

    The concurrent administration of bupropion hydrochloride tablets 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 bupropion hydrochloride tablets.

    Bupropion hydrochloride tablets are contraindicated in patients who have shown an allergic response to bupropion or the other ingredients that make up bupropion hydrochloride tablets.

    Close
  • WARNINGS

    Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders

    Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

    The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1.


    Table 1
    Age Range

    Drug-Placebo Difference in

    Number of Cases of Suicidality

    per 1,000 Patients Treated
    Increases Compared to Placebo
    <18 14 additional cases
    18-24 5 additional cases
    Decreases Compared to Placebo
    25-64 1 fewer case
    ≥65 6 fewer cases

    No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

    It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

    All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

    The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

    Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

    Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for bupropion hydrochloride should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

    Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment

    Bupropion hydrochloride, bupropion hydrochloride, the sustained-release formulation, and bupropion hydrochloride, the extended-release forumlation, are not approved for smoking cessation treatment, but bupropion under the name ZYBAN (bupropion hydrochloride) Sustained-Release Tablets is approved for this use. Serious neuropsychiatric symptoms have been reported in patients taking bupropion for smoking cessation (see BOXED WARNING, ADVERSE REACTIONS). These have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Some reported cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking. Depressed mood may be a symptom of nicotine withdrawal. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these symptoms have occurred in patients taking bupropion who continued to smoke. When symptoms were reported, most were during bupropion treatment, but some were following discontinuation of bupropion therapy.

    These events have occurred in patients with and without pre-existing psychiatric disease; some have experienced worsening of their psychiatric illnesses. All patients being treated with bupropion as part of smoking cessation treatment should be observed for neuropsychiatric symptoms or worsening of pre-existing psychiatric illness.

    Patients with serious psychiatric illness such as schizophrenia, bipolar disorder, and major depressive disorder did not participate in the pre-marketing studies of ZYBAN.

    Advise patients and caregivers that the patient using bupropion for smoking cessation should stop taking bupropion and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of ZYBAN was reported, although in some cases the symptoms persisted, therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

    The risks of using bupropion for smoking cessation should be weighed against the benefits of its use. ZYBAN has been demonstrated to increase the likelihood of abstinence from smoking for as long as six months compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial.

    Screening Patients for Bipolar Disorder

    A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that bupropion hydrochloride tablets is not approved for use in treating bipolar depression.

    Bupropion-Containing Products

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

    Seizures

    Bupropion is associated with seizures in approximately 0.4% (4/1,000) of patients treated at doses up to 450 mg/day. This incidence of seizures may exceed that of other marketed antidepressants by as much as 4-fold. This relative risk is only an approximate estimate because no direct comparative studies have been conducted. The estimated seizure incidence for bupropion hydrochloride tablets increases almost tenfold between 450 and 600 mg/day, which is twice the usually required daily dose (300 mg) and one and one-third the maximum recommended daily dose (450 mg). Given the wide variability among individuals and their capacity to metabolize and eliminate drugs this disproportionate increase in seizure incidence with dose incrementation calls for caution in dosing.

    During the initial development, 25 among approximately 2,400 patients treated with bupropion hydrochloride tablets experienced seizures. At the time of seizure, 7 patients were receiving daily doses of 450 mg or below for an incidence of 0.33% (3/1,000) within the recommended dose range. Twelve patients experienced seizures at 600 mg/day (2.3% incidence); 6 additional patients had seizures at daily doses between 600 and 900 mg (2.8% incidence).

    A separate, prospective study was conducted to determine the incidence of seizure during an 8-week treatment exposure in approximately 3,200 additional patients who received daily doses of up to 450 mg. Patients were permitted to continue treatment beyond 8 weeks if clinically indicated. Eight seizures occurred during the initial 8-week treatment period and 5 seizures were reported in patients continuing treatment beyond 8 weeks, resulting in a total seizure incidence of 0.4%.

    The risk of seizure appears to be strongly associated with dose. Sudden and large increments in dose may contribute to increased risk. While many seizures occurred early in the course of treatment, some seizures did occur after several weeks at fixed dose. Bupropion hydrochloride tablets should be discontinued and not restarted in patients who experience a seizure while on treatment.

    The risk of seizure is also related to patient factors, clinical situations, and concomitant medications, which must be considered in selection of patients for therapy with bupropion hydrochloride tablets.

    • Patient factors: Predisposing factors that may increase the risk of seizure with bupropion use include history of head trauma or prior seizure, central nervous system (CNS) tumor, the presence of severe hepatic cirrhosis, and concomitant medications that lower seizure threshold.
    • Clinical situations: Circumstances associated with an increased seizure risk include, among others, excessive use of alcohol or sedatives (including benzodiazepines); addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; and diabetes treated with oral hypoglycemics or insulin.
    • Concomitant medications: Many medications (e.g., antipsychotics, antidepressants, theophylline, systemic steroids) are known to lower seizure threshold.

    Recommendations for Reducing the Risk of Seizure

    Retrospective analysis of clinical experience gained during the development of bupropion hydrochloride tablets suggests that the risk of seizure may be minimized if

    • the total daily dose of bupropion hydrochloride tablets does not exceed 450 mg,
    • the daily dose is administered 3 times daily, with each single dose not to exceed 150 mg to avoid high peak concentrations of bupropion and/or its metabolites, and
    • the rate of incrementation of dose is very gradual.

    Bupropion hydrochloride tablets should be administered with extreme caution to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure, or patients treated with other agents (e.g., antipsychotics, other antidepressants, theophylline, systemic steroids, etc.) that lower seizure threshold.

    Hepatic Impairment

    Bupropion hydrochloride tablets should be used with extreme caution in patients with severe hepatic cirrhosis. In these patients a reduced dose and/or frequency is required, as peak bupropion, as well as AUC, levels are substantially increased and accumulation is likely to occur in such patients to a greater extent than usual. The dose should not exceed 75 mg once a day in these patients (see CLINICAL PHARMACOLOGY, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).

    Potential for Hepatotoxicity

    In rats receiving large doses of bupropion chronically, there was an increase in incidence of hepatic hyperplastic nodules and hepatocellular hypertrophy. In dogs receiving large doses of bupropion chronically, various histologic changes were seen in the liver, and laboratory tests suggesting mild hepatocellular injury were noted.

    Close
  • ADVERSE REACTIONS

    (See also WARNINGS and PRECAUTIONS)

    Adverse events commonly encountered in patients treated with bupropion hydrochloride tablets are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, and tremor.

    Adverse events were sufficiently troublesome to cause discontinuation of treatment with bupropion hydrochloride tablets in approximately 10% of the 2,400 patients and volunteers who participated in clinical trials during the product’s initial development. The more common events causing discontinuation include neuropsychiatric disturbances (3.0%), primarily agitation and abnormalities in mental status; gastrointestinal disturbances (2.1%), primarily nausea and vomiting; neurological disturbances (1.7%), primarily seizures, headaches, and sleep disturbances; and dermatologic problems (1.4%), primarily rashes. It is important to note, however, that many of these events occurred at doses that exceed the recommended daily dose.

    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. Consequently, Table 2 is presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of bupropion hydrochloride tablets under relatively similar conditions of daily dosage (300 to 600 mg), setting, and duration (3 to 4 weeks). 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 must differ from those which 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 tablets is provided in WARNINGS and PRECAUTIONS.

    Table 2. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials* (Percent of Patients Reporting)
    Adverse Experience

    Bupropion

    Hydrochloride

    Tablets

    Patients

    (n = 323)

    Placebo

    Patients

    (n = 185)
    *
    Events reported by at least 1% of patients receiving bupropion hydrochloride tablets are included.
    CARDIOVASCULAR
    Cardiac arrhythmias 5.3 4.3
    Dizziness 22.3 16.2
    Hypertension 4.3 1.6
    Hypotension 2.5 2.2
    Palpitations 3.7 2.2
    Syncope 1.2 0.5
    Tachycardia 10.8 8.6
    DERMATOLOGIC
    Pruritus 2.2 0.0
    Rash 8.0 6.5
    GASTROINTESTINAL
    Anorexia 18.3 18.4
    Appetite increase 3.7 2.2
    Constipation 26.0 17.3
    Diarrhea 6.8 8.6
    Dyspepsia 3.1 2.2
    Nausea/vomiting 22.9 18.9
    Weight gain 13.6 22.7
    Weight loss 23.2 23.2
    GENITOURINARY
    Impotence 3.4 3.1
    Menstrual complaints 4.7 1.1
    Urinary frequency 2.5 2.2
    Urinary retention 1.9 2.2
    MUSCULOSKELETAL
    Arthritis 3.1 2.7
    NEUROLOGICAL
    Akathisia 1.5 1.1
    Akinesia/bradykinesia 8.0 8.6
    Cutaneous temperature disturbance 1.9 1.6
    Dry mouth 27.6 18.4
    Excessive sweating 22.3 14.6
    Headache/migraine 25.7 22.2
    Impaired sleep quality 4.0 1.6
    Increased salivary flow 3.4 3.8
    Insomnia 18.6 15.7
    Muscle spasms 1.9 3.2
    Pseudoparkinsonism 1.5 1.6
    Sedation 19.8 19.5
    Sensory disturbance 4.0 3.2
    Tremor 21.1 7.6
    NEUROPSYCHIATRIC
    Agitation 31.9 22.2
    Anxiety 3.1 1.1
    Confusion 8.4 4.9
    Decreased libido 3.1 1.6
    Delusions 1.2 1.1
    Disturbed concentration 3.1 3.8
    Euphoria 1.2 0.5
    Hostility 5.6 3.8
    NONSPECIFIC
    Fatigue 5.0 8.6
    Fever/chills 1.2 0.5
    RESPIRATORY
    Upper respiratory complaints 5.0 11.4
    SPECIAL SENSES
    Auditory disturbance 5.3 3.2
    Blurred vision 14.6 10.3
    Gustatory disturbance 3.1 1.1

    Other Events Observed During the Development of Bupropion Hydrochloride Tablets

    The conditions and duration of exposure to bupropion hydrochloride tablets varied greatly, and a substantial proportion of the experience was gained in open and uncontrolled clinical settings. During this experience, numerous adverse events were reported; however, without appropriate controls, it is impossible to determine with certainty which events were or were not caused by bupropion hydrochloride tablets. The following enumeration is organized by organ system and describes events in terms of their relative frequency of reporting in the data base. Events of major clinical importance are also described in WARNINGS and PRECAUTIONS.

    The following definitions of frequency are used: 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.

    Cardiovascular

    Frequent was edema; infrequent were chest pain, electrocardiogram (ECG) abnormalities (premature beats and nonspecific ST-T changes), and shortness of breath/dyspnea; rare were flushing, pallor, phlebitis, and myocardial infarction.

    Dermatologic

    Frequent were nonspecific rashes; infrequent were alopecia and dry skin; rare were change in hair color, hirsutism, and acne.

    Endocrine

    Infrequent was gynecomastia; rare were glycosuria and hormone level change.

    Gastrointestinal

    Infrequent were dysphagia, thirst disturbance, and liver damage/jaundice; rare were rectal complaints, colitis, gastrointestinal bleeding, intestinal perforation, and stomach ulcer.

    Genitourinary

    Frequent was nocturia; infrequent were vaginal irritation, testicular swelling, urinary tract infection, painful erection, and retarded ejaculation; rare were dysuria, enuresis, urinary incontinence, menopause, ovarian disorder, pelvic infection, cystitis, dyspareunia, and painful ejaculation.

    Hematologic/Oncologic

    Rare were lymphadenopathy, anemia, and pancytopenia.

    Musculoskeletal

    Rare was musculoskeletal chest pain.

    Neurological

    (See WARNINGS)

    Frequent were ataxia/incoordination, seizure, myoclonus, dyskinesia, and dystonia; infrequent were mydriasis, vertigo, and dysarthria; rare were electroencephalogram (EEG) abnormality, abnormal neurological exam, impaired attention, sciatica, and aphasia.

    Neuropsychiatric

    (See PRECAUTIONS)

    Frequent were mania/hypomania, increased libido, hallucinations, decrease in sexual function, and depression; infrequent were memory impairment, depersonalization, psychosis, dysphoria, mood instability, paranoia, formal thought disorder, and frigidity; rare was suicidal ideation.

    Oral Complaints

    Frequent was stomatitis; infrequent were toothache, bruxism, gum irritation, and oral edema; rare was glossitis.

    Respiratory

    Infrequent were bronchitis and shortness of breath/dyspnea; rare were epistaxis, rate or rhythm disorder, pneumonia, and pulmonary embolism.

    Special Senses

    Infrequent was visual disturbance; rare was diplopia.

    Nonspecific

    Frequent were flu-like symptoms; infrequent was nonspecific pain; rare were body odor, surgically related pain, infection, medication reaction, and overdose.

    Postintroduction Reports

    Voluntary reports of adverse events temporally associated with bupropion that have been received since market introduction and which may have no causal relationship with the drug include the following:

    Body (General)

    Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity. These symptoms may resemble serum sickness (see PRECAUTIONS).

    Cardiovascular

    Hypertension (in some cases severe, see PRECAUTIONS), orthostatic hypotension, third degree heart block

    Endocrine

    Syndrome of inappropriate antidiuretic hormone secretion, hyperglycemia, hypoglycemia

    Gastrointestinal

    Esophagitis, hepatitis, liver damage

    Hemic and Lymphatic

    Ecchymosis, leukocytosis, leukopenia, thrombocytopenia. Altered PT and/or INR, infrequently associated with hemorrhagic or thrombotic complications, were observed when bupropion was coadministered with warfarin.

    Musculoskeletal

    Arthralgia, myalgia, muscle rigidity/fever/rhabdomyolysis, muscle weakness

    Nervous

    Aggression, coma, completed suicide, delirium, dream abnormalities, paranoid ideation, paresthesia, restlessness, suicide attempt, unmasking of tardive dyskinesia

    Skin and Appendages

    Stevens-Johnson syndrome, angioedema, exfoliative dermatitis, urticaria

    Special Senses

    Tinnitus, increased intraocular pressure

    Close
  • DRUG ABUSE AND DEPENDENCE

    Humans

    Controlled clinical studies 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/excitement.

    In a population of individuals experienced with drugs of abuse, a single dose of 400 mg of bupropion hydrochloride tablets 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 predict the abuse potential of drugs reliably. 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 have shown that bupropion exhibits some pharmacologic actions common to psychostimulants including increases in locomotor activity and the production of a mild stereotyped behavior and increases in rates of responding in several schedule-controlled behavior paradigms. Drug discrimination studies in rats showed stimulus generalization between bupropion and amphetamine and other psychostimulants. Rhesus monkeys have been shown to self-administer bupropion intravenously.

    Close
  • 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 tablets, 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 listed in the Physicians’ Desk Reference (PDR).

    Close
  • DOSAGE AND ADMINISTRATION

    General Dosing Considerations

    It is particularly important to administer bupropion hydrochloride tablets in a manner most likely to minimize the risk of seizure (see WARNINGS). Increases in dose should not exceed 100 mg/day in a 3-day period. 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.

    No single dose of bupropion hydrochloride tablets should exceed 150 mg. Bupropion hydrochloride tablets should be administered 3 times daily, preferably with at least 6 hours between successive doses.

    Usual Dosage for Adults

    The usual adult dose is 300 mg/day, given 3 times daily. Dosing should begin at 200 mg/day, given as 100 mg twice daily. Based on clinical response, this dose may be increased to 300 mg/day, given as 100 mg 3 times daily, no sooner than 3 days after beginning therapy (see Table 3).

    Table 3. Dosing Regimen

    Treatment

    Day

    Total

    Daily Dose

    Tablet

    Strength
    Number of Tablets
    Morning Midday Evening
    1 200 mg 100 mg 1 0 1
    4 300 mg 100 mg 1 1 1

    Increasing the Dosage Above 300 mg/Day

    As with other antidepressants, the full antidepressant effect of bupropion hydrochloride tablets may not be evident until 4 weeks of treatment or longer. An increase in dosage, up to a maximum of 450 mg/day, given in divided doses of not more than 150 mg each, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 300 mg/day. Dosing above 300 mg/day may be accomplished using the 75 or 100 mg tablets. The 100 mg tablet must be administered 4 times daily with at least 4 hours between successive doses, in order not to exceed the limit of 150 mg in a single dose. Bupropion hydrochloride tablets should be discontinued in patients who do not demonstrate an adequate response after an appropriate period of treatment at 450 mg/day.

    Maintenance Treatment

    The lowest dose that maintains remission is recommended. Although it is not known how long the patient should remain on bupropion hydrochloride tablets, it is generally recognized that acute episodes of depression require several months or longer of antidepressant drug treatment.

    Dosage Adjustment for Patients with Impaired Hepatic Function

    Bupropion hydrochloride tablets should be used with extreme caution in patients with severe hepatic cirrhosis. The dose should not exceed 75 mg once a day in these patients. Bupropion hydrochloride tablets 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 tablets 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).

    Close
  • MEDICATION GUIDE

    BuPROPion Hydrochloride Tablets, USP

    Read this Medication Guide carefully before you start using bupropion hydrochloride tablets 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 tablets, 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 Tablets?”

    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 list 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 tablets 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 tablets is 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 tablets?

    • Seizures. There is a chance of having a seizure (convulsion, fit) with bupropion hydrochloride tablets, especially in people:
      • with certain medical problems.
      • who take certain medicines.

      The chance of having seizures increases with higher doses of bupropion hydrochloride tablets. For more information, see the sections “Who should not take bupropion hydrochloride tablets?” and “What should I tell my doctor before using bupropion hydrochloride tablets?” 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 tablets unless your doctor has said it is okay to take them.

      If you have a seizure while taking bupropion hydrochloride tablets, stop taking the tablets and call your doctor right away. Do not take bupropion hydrochloride tablets again if you have a seizure.

    • High blood pressure (hypertension). Some people get high blood pressure, that can be severe, while taking bupropion hydrochloride tablets. 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 reaction to bupropion hydrochloride tablets. Stop taking bupropion hydrochloride tablets 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 tablets, 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 tablets?

    Bupropion hydrochloride tablets are a prescription medicine used to treat adults with a certain type of depression called major depressive disorder.

    Who should not take bupropion hydrochloride tablets?

    Do not take bupropion hydrochloride tablets 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 SR Sustained-Release Tablets or Wellbutrin XL Extended-Release Tablets. Bupropion is the same ingredient that is in bupropion hydrochloride tablets, USP.
    • 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.
    • have taken within the last 14 days medicine for depression called a monoamine oxidase inhibitor (MAOI), such as NARDIL® (phenelzine sulfate), PARNATE® (tranylcypromine sulfate), or MARPLAN® (isocarboxazid).
    • have or had an eating disorder such as anorexia nervosa or bulimia.
    • are allergic to the active ingredient in bupropion hydrochloride tablets, bupropion, or to any of the inactive ingredients. See the end of this leaflet for a complete list of ingredients in bupropion hydrochloride tablets.

    What should I tell my doctor before using bupropion hydrochloride tablets?

    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 tablets can harm your unborn baby.
    • are breastfeeding. Bupropion hydrochloride tablets passes through your milk. It is not known if bupropion hydrochloride 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 non-prescription 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 tablets.

    How should I take bupropion hydrochloride tablets?

    • Take bupropion hydrochloride tablets exactly as prescribed by your doctor.
    • Take bupropion hydrochloride tablets at the same time each day.
    • Take your doses of bupropion hydrochloride tablets at least 6 hours apart.
    • You may take bupropion hydrochloride tablets 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 many bupropion hydrochloride tablets can increase your chance of having a seizure.
    • If you take too many bupropion hydrochloride tablets, or overdose, call your local emergency room or poison control center right away.
    • Do not take any other medicines while using bupropion hydrochloride tablets unless your doctor has told you it is okay.
    • It may take several weeks for you to feel that bupropion hydrochloride tablets are working. Once you feel better, it is important to keep taking bupropion hydrochloride tablets exactly as directed by your doctor. Call your doctor if you do not feel bupropion hydrochloride tablets are working for you.
    • Do not change your dose or stop taking bupropion hydrochloride tablets without talking with your doctor first.

    What should I avoid while taking bupropion hydrochloride tablets?

    • Do not drink a lot of alcohol while taking bupropion hydrochloride tablets. 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 having seizures.
    • Do not drive a car or use heavy machinery until you know how bupropion hydrochloride tablets affects you. Bupropion hydrochloride tablets can impair your ability to perform these tasks.

    What are possible side effects of bupropion hydrochloride tablets?

    Bupropion hydrochloride tablets 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 tablets 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 trouble sleeping, do not take your medicine too close to bedtime.

    These are not all the side effects of bupropion hydrochloride tablets. For a complete list, 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 tablets?

    • Store bupropion hydrochloride tablets at room temperature. Store out of direct sunlight. Keep bupropion hydrochloride tablets in its tightly closed bottle.

    General Information about bupropion hydrochloride tablets.

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

    This Medication Guide summarizes important information about bupropion hydrochloride tablets. For more information, talk to your doctor. You can ask your doctor or pharmacist for information about bupropion hydrochloride tablets that is written for health professionals.

    What are the ingredients in bupropion hydrochloride tablets?

    Active ingredient: bupropion hydrochloride.

    Inactive ingredients: FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, hydroxypropyl methylcellulose, microcrystalline cellulose, potassium chloride, pregelatinized starch, stearic acid, titanium dioxide, and triethyl citrate.

    The following are registered trademarks of their respective manufacturers: NARDIL®/Warner Lambert Company; MARPLAN®/Oxford Pharmaceutical Services, Inc.; KALETRA®/Abbott Laboratories; PARNATE®, Wellbutrin SR®, Wellbutrin XL®, ZYBAN®/GlaxoSmith Kline.

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

    Close
  • Bupropion 100mg Tablet
  • INGREDIENTS AND APPEARANCE
    BUPROPION HYDROCHLORIDE 
    bupropion hydrochloride tablet, film coated
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-3233(NDC:0781-1064)
    Route of Administration ORAL DEA Schedule     
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    BUPROPION HYDROCHLORIDE (UNII: ZG7E5POY8O) (BUPROPION - UNII:01ZG3TPX31) BUPROPION HYDROCHLORIDE 100 mg
    Inactive Ingredients
    Ingredient Name Strength
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    HYPROMELLOSE 2910 (15 MPA.S) (UNII: 36SFW2JZ0W)  
    POTASSIUM CHLORIDE (UNII: 660YQ98I10)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    STEARIC ACID (UNII: 4ELV7Z65AP)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    TRIETHYL CITRATE (UNII: 8Z96QXD6UM)  
    Product Characteristics
    Color PURPLE (Lavender) Score no score
    Shape ROUND Size 11mm
    Flavor Imprint Code GG930
    Contains     
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:63629-3233-1 60 in 1 BOTTLE
    2 NDC:63629-3233-2 30 in 1 BOTTLE
    3 NDC:63629-3233-3 100 in 1 BOTTLE
    4 NDC:63629-3233-4 90 in 1 BOTTLE
    5 NDC:63629-3233-5 120 in 1 BOTTLE
    6 NDC:63629-3233-6 15 in 1 BOTTLE
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA075584 02/07/2000
    Labeler - Bryant Ranch Prepack (171714327)
    Registrant - Bryant Ranch Prepack (171714327)
    Establishment
    Name Address ID/FEI Business Operations
    Bryant Ranch Prepack 171714327 REPACK(63629-3233) , RELABEL(63629-3233)
    Close