section name header

Introduction ⬇

AHFS Class:

Generic Name(s):

Bupropion is an aminoketone-derivative antidepressant and smoking deterrent.1,43,142,143,168,226,227

Uses ⬆ ⬇

[Section Outline]

Major Depressive Disorder !!navigator!!

Bupropion is used in the treatment of major depressive disorder as defined by the Diagnostic and Statistical Manual (DSM).1,127,128,129,131,132,142,168,179,180,226,227 Efficacy of conventional bupropion hydrochloride tablets for long-term use (i.e., >6 weeks) as an antidepressant has not been established by controlled studies; if conventional or extended-release tablets of the drug are used for extended periods, the need for continued therapy should be reassessed periodically.1,142,168,226 Systematic evaluation of bupropion hydrochloride extended-release tablets has shown that antidepressant efficacy is maintained for periods of up to 44 weeks in patients receiving a dosage of 150 mg twice daily.142,168

For information on the use of bupropion in fixed combination with dextromethorphan for the treatment of major depressive disorder in adults, see Dextromethorphan Hydrobromide and Bupropion Hydrochloride 28:16.04.92.

Clinical Experience

Efficacy of bupropion for the management of major depression has been established in a controlled outpatient study of approximately 6 weeks' duration and in 2 controlled inpatient studies of approximately 4 weeks' duration.1,3,142 Bupropion hydrochloride was administered as conventional tablets in these studies,142 and the dosage received by 78% of the patients in one of the studies of 4 weeks' duration was ≤450 mg daily, although the dosage was titratable to 600 mg daily.142 Efficacy of bupropion in these studies was demonstrated by improvement in total score on the Hamilton rating scale for depression (HAM-D), in item 1 of the HAM-D that measures depressed mood, and in the Clinical Global Impressions of Severity of Illness (CGI-S) scale.142 Patients received 300 or 450 mg daily of bupropion hydrochloride in the second study of 4 weeks' duration, which demonstrated efficacy only of the higher dosage, as indicated by improvement in total score on the HAM-D and in the CGI-S scale.142 However, in the study of 6 weeks' duration that evaluated the efficacy of 300 mg daily of bupropion hydrochloride, the drug was superior to placebo in improvement of total score on the HAM-D, which was the primary measure of efficacy.3,142 In addition, depressed mood, as measured by item 1 on the HAM-D, was improved in patients treated with bupropion.142 The drug also was superior to placebo in improvement of scores on the Montgomery-Asberg Depression Rating Scale, the CGI-S scale, and the Clinical Global Impressions of Improvement (CGI-I) scale.3,142 Although clinical studies specifically establishing the efficacy of extended-release tablets of bupropion in the management of major depression have not been performed to date,142,168 the extended-release, film-coated tablet (e.g., Wellbutrin® SR) has been shown to be bioequivalent at steady state to conventional tablets of bupropion, and antidepressant efficacy was maintained for up to 44 weeks in a placebo-controlled study.142 In addition, the extended-release tablet (Wellbutrin® XL) has been shown to be bioequivalent to the conventional and the extended-release, film-coated tablets.168 Bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL®) and bupropion hydrobromide extended-release tablets (Aplenzin®) have been shown to be bioequivalent to bupropion hydrochloride extended-release tablets (e.g., Wellbutrin® XL),226,227 Bupropion hydrobromide doses of 174, 348, or 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, or 450 mg, respectively.227

Clinical studies have shown that the antidepressant effect of usual dosages of bupropion in patients with moderate to severe depression is greater than that of placebo and comparable to that of usual dosages of tricyclic antidepressants, fluoxetine, or trazodone.2,3,44,45,53,54,92,93 Bupropion generally was not distinguishable from these antidepressant agents in measures of efficacy that included the HAM-D scale, the CGI-S scale, the CGI-I scale, and the Hamilton rating scale for anxiety (HAM-A).2,45,53,54,92,93,142 However, other antidepressants were associated with greater improvement on the HAM-D rating scale during some weeks of the evaluations principally because of greater improvement in the sleep factor of this scale observed with tricyclic antidepressants or trazodone in comparison to bupropion.53,92,93

Because of differences in the adverse effect profile between bupropion and tricyclic antidepressants, particularly less frequent anticholinergic effects, cardiovascular effects, antihistaminic effects, and weight gain with bupropion therapy, bupropion may be preferred for patients in whom such effects are not tolerated or are of potential concern.2,23,44,104,127,128,133 In a study that compared bupropion with doxepin, discontinuance of therapy because of adverse effects resulted mainly from anticholinergic effects, particularly drowsiness, in patients treated with doxepin but from a variety of adverse effects in patients treated with bupropion.53,104 After 13 weeks of therapy, patients who received doxepin had gained 2.73 kg while those who received bupropion had lost 1.36 kg.53 Orthostatic hypotension that required discontinuance of the antidepressant agent occurred with some frequency with imipramine but not with bupropion.33,104 In addition, in a large 102-center prospective study, 54% of patients who responded poorly to previous antidepressant therapy responded to bupropion therapy, and 63% of patients who poorly tolerated previous antidepressant therapy tolerated bupropion; 81% of patients who completed an initial 8-week treatment phase in this study elected to receive maintenance therapy with bupropion.23,44 Although the possibility of bupropion-induced seizures should be considered in weighing the benefits versus risks compared with alternative therapies,1 the risk of seizures appears to be within clinically acceptable parameters in patients without preexisting risk.23,24,44,141

Bupropion also may be preferable because of its minimal adverse effects and possibly beneficial effects on sexual functioning.1,2,44,104,112,118,178 Most men with depression who experienced sexual dysfunction (e.g., decreased libido, partial erectile failure) during therapy with another antidepressant (e.g., tricyclic antidepressant, maprotiline, trazodone, tranylcypromine) did not have such impairment with bupropion.2,44,104,112,134 In a study comparing the adverse sexual effects of bupropion with those of certain selective serotonin-reuptake inhibitors (SSRIs; i.e., fluoxetine, paroxetine, and sertraline), statistically significant increases in libido, sexual arousal, intensity of orgasm, and/or duration of orgasm were reported in most bupropion-treated patients compared with those reported before the onset of illness, while SSRI therapy significantly reduced these aspects of sexual functioning in most of the patients studied.178 In another study, dysfunctional orgasm resolved when antidepressant therapy was changed from fluoxetine to bupropion in most men and women who developed orgasm failure and/or delay with fluoxetine.2,118 Libido and satisfaction with overall sexual functioning also were improved with bupropion.104,118 Limited experience suggests that bupropion also may be useful in the management of sexual dysfunction associated with fluoxetine.125 Sexual dysfunction (e.g., decreased libido, erectile and orgasmic impairment) associated with fluoxetine was reported to respond to concomitant administration of 75 mg daily of bupropion hydrochloride.2,125

Bupropion administered alone or concurrently with other antidepressant agents may be useful in patients with refractory depression.179,180 In the large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) effectiveness trial, patients with major depressive disorder who did not respond to or could not tolerate citalopram (an SSRI) were randomized to switch to extended-release (“sustained-release”) bupropion, sertraline (another SSRI), or extended-release venlafaxine (a selective serotonin- and norepinephrine-reuptake inhibitor) as a second step of treatment (level 2).180 Remission rates as assessed by the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Quick Inventory of Depressive Symptomatology—Self Report (QIDS-SR-16) were approximately 21 and 26% for extended-release bupropion, 18 and 27% for sertraline, and 25 and 25% for extended-release venlafaxine therapy, respectively; response rates as assessed by the QIDS-SR-16 were 26%, 27%, and 28% for extended-release bupropion, sertraline, and extended-release venlafaxine therapy, respectively.180 These results suggest that after unsuccessful initial treatment of depressed patients with an SSRI, approximately 25% of patients will achieve remission after therapy is switched to another antidepressant, and either another SSRI (e.g., sertraline) or an agent from another class (e.g., bupropion, venlafaxine) may be reasonable alternative antidepressants in patients not responding to initial SSRI therapy.180

In a second STAR*D level 2 trial, patients with major depressive disorder who did not respond to or could not tolerate SSRI therapy (citalopram) were randomized to receive either extended-release (“sustained-release”) bupropion or buspirone therapy in addition to citalopram.179 Although both extended-release bupropion and buspirone were found to produce similar remission rates, extended-release bupropion produced a greater reduction in the number and severity of symptoms and a lower rate of drug discontinuance than buspirone in this large-scale, effectiveness trial.179 These results suggest that augmentation of SSRI therapy with extended-release bupropion may be useful in some patients with refractory depression.179

Clinical Perspective

The American Psychiatric Association (APA) has published clinical guidelines for the treatment of major depressive disorder in adults.160 According to these guidelines, the goals of treatment are to induce remission of the major depressive episode and achieve a full return to the patient's baseline level of functioning.160 Data on comparative efficacy of various antidepressants show generally comparable effectiveness between and within classes of antidepressant agents.160 The choice of agent should be directed by symptoms, past treatment response, patient preference, cost and availability, comorbid conditions/contraindications, concomitant drug therapy/interactions, and potential adverse effects.160 For most patients, bupropion is recommended as an option for first-line pharmacologic therapy for major depressive disorder.160

Patients in whom bupropion may be a particularly good option include those also seeking assistance with smoking cessation; patients concerned about weight gain or who have experienced weight gain with other antidepressants; patients experiencing adverse sexual effects with other antidepressants; patients who are sensitive to anticholinergic effects (e.g., patients with dementia); patients experiencing fatigue or sleepiness; and, possibly, patients with Parkinson's disease.160 Bupropion may be less well tolerated than other antidepressants in patients with severe anxiety, and the drug should be used cautiously in patients with a history of psychotic disorders.160 In addition, bupropion is contraindicated in patients with a history of anorexia nervosa, bulimia, or seizure disorders and in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.1

Seasonal Affective Disorder !!navigator!!

Bupropion hydrochloride extended-release tablets (Wellbutrin® XL) and bupropion hydrobromide extended-release tablets (Aplenzin®) are used for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).168,169,170,171,227 SAD is characterized by recurrent major depressive episodes, most commonly occurring during the autumn and/or winter months.107,168 Although patients with SAD may have depressive episodes during other times of the year, the number of seasonal episodes should substantially outnumber the number of nonseasonal episodes during the individual's lifetime for a diagnosis of SAD to be considered.107

Efficacy of bupropion for the prevention of seasonal major depressive episodes associated with SAD has been established in 3 double-blind, placebo-controlled trials in adult outpatients with a history of major depressive disorder with an autumn-winter seasonal pattern (as defined by DSM-IV criteria).107,168,169 Bupropion therapy was initiated prior to symptom onset during the autumn (September to November), continued through the winter months, and discontinued following a 2-week tapering period beginning the first week of spring (the fourth week of March), which resulted in a treatment duration of approximately 4-6 months for the majority of patients.168,169 Patients were randomized to receive either placebo or 150 mg of bupropion hydrochloride as extended-release tablets once daily for 1 week, then the dosage was titrated upward to 300 mg once daily.168,169 Patients judged by the investigator to be unlikely or unable to tolerate the 300-mg daily dosage were allowed to continue to receive 150 mg daily or to have their dosage reduced to 150 mg once daily; mean dosages in the 3 studies ranged from 257-280 mg once daily.168,169 In these 3 trials, a substantially higher percentage of patients receiving bupropion extended-release tablets were depression-free at the end of treatment compared with those receiving placebo (81.4 vs 69.7%, 87.2 vs 78.7%, and 84 vs 69%, respectively, for studies 1, 2, and 3, respectively); the depression-free rate for the 3 studies combined was 84.3% for extended-release bupropion tablets and 72% for placebo.168,169

Smoking Cessation !!navigator!!

Bupropion hydrochloride extended-release (SR) 150-mg tablets are used as an adjunct in the cessation of smoking.143,145,146,147,152 Such therapy may be combined with nicotine replacement therapy if necessary.143,152 However, the manufacturer states that before patients receive this combination of therapies, the labeling for both bupropion and nicotine should be consulted and recommends that patients who receive bupropion and nicotine concurrently be monitored for the development of hypertension related to such therapy.143

Clinical Experience

The efficacy of bupropion extended-release tablets as adjunctive therapy for smoking cessation has been established in controlled studies of smokers of ≥15 cigarettes daily, who did not have an underlying depressive disorder.143,145,146 Patients were treated with bupropion in conjunction with individual counseling.143,145 Cessation of smoking was defined as total abstinence, as determined with patients' daily diaries and verified by measurement of expiratory carbon monoxide, during the fourth through seventh week of treatment.143,145 Treatment over 7 weeks with bupropion hydrochloride or placebo resulted in 1-year cessation of smoking in a greater proportion of patients treated with the drug at a dosage of 150 or 300 mg daily but not in those receiving 100 mg daily.143,145 Cessation of smoking was achieved at the end of 7 weeks of treatment in 36-44, 27-39, or 17-19% of patients who received 300 mg daily of bupropion hydrochloride, 150 mg daily of the drug, or placebo, respectively.143,145 Maintenance of abstinence was observed with bupropion hydrochloride at a dosage of 300 mg daily.143 At follow-up during the twelfth week, abstinence continued in 25-30 or 14% of patients who had received bupropion hydrochloride at 300 mg daily or placebo, respectively,143,145 and at follow-up during the twenty-sixth week, abstinence continued in 19-27 or 11-16% of patients who had received bupropion hydrochloride at 300 mg daily or placebo, respectively.143

Treatment over 9 weeks with bupropion hydrochloride at a dosage of 300 mg daily, transdermal nicotine at a dosage of 21 mg/24 hours, the combination of 300 mg daily of bupropion hydrochloride and transdermal nicotine at 21 mg/24 hours, or placebo resulted in cessation of smoking in a greater proportion of patients treated with bupropion, transdermal nicotine, or the combination of bupropion and transdermal nicotine than in those receiving placebo.143 Cessation of smoking was achieved during weeks 4-7 in 49, 36, 58, or 23% of patients who received bupropion, transdermal nicotine, the combination of bupropion and transdermal nicotine, or placebo, respectively.143 At follow-up during the tenth week, abstinence was observed in 46, 32, 51, or 20% of patients who had received bupropion, transdermal nicotine, the combination of bupropion and transdermal nicotine, or placebo, respectively.143 Additionally, when these patients were assessed at 26 weeks, cessation of smoking continued to be observed in 30, 33, and 13% of patients who received bupropion, the combination of bupropion and transdermal nicotine, or placebo, respectively.143 A final assessment was performed at 52 weeks and abstinence continued to be observed in 23, 28, and 8% of patients who received bupropion, the combination of bupropion and nicotine, or placebo, respectively.143 The manufacturer states that because the comparisons between bupropion extended-release tablets, transdermal nicotine, or the combination of these products have not been replicated, these data should not be interpreted as demonstrating superiority of any individual treatment protocol.143

Another clinical study also reviewed long-term maintenance treatment with bupropion.143 Patients received bupropion hydrochloride extended-release tablets at a dosage of 300 mg daily for 7 weeks; therapy was continued in the patients who achieved cessation of smoking at 7 weeks with either bupropion hydrochloride extended-release tablets or placebo.143 At 6-month follow-up, abstinence continued in 55% of patients receiving bupropion compared with 44% of patients who received placebo therapy.143

The safety and efficacy of bupropion extended-release tablets as adjunctive therapy for smoking cessation in patients with chronic obstructive pulmonary disease (COPD) was established in a clinical trial in adults with mild to moderate COPD (FEV1≥35%, FEV1/FVC ≤70%) and a diagnosis of chronic bronchitis, emphysema, and/or small airways disease.143 Treatment over a 12 week period with bupropion or placebo resulted in cessation of smoking during the final four weeks of the study in 22 or 12% of patients, respectively.143

Since efficacy in clinical studies is influenced by the population selected, a lower rate of cessation of smoking is possible with use of bupropion in an unselected population.143 The reported cessation rates in patients receiving bupropion were similar in patients who had and had not previously received nicotine replacement therapy for the cessation of smoking.143 Withdrawal symptoms, especially irritability, frustration, anger, anxiety, difficulty concentrating, restlessness, and depressed mood or negative affect, were reduced with bupropion compared with placebo.143,145 Craving for cigarettes or urge to smoke appeared to be reduced with bupropion compared with placebo.143

Clinical Perspective

The US Public Health Service (USPHS) guideline for the treatment of tobacco use and dependence recommends bupropion (as extended-release tablets) as one of several first-line drugs that may reliably increase long-term smoking abstinence rates.152 Nicotine (tobacco) dependence is a chronic relapsing disorder that requires ongoing assessment and often repeated intervention.152 Because effective nicotine dependence therapies are available, every patient should be offered effective treatment, and those who are unwilling to attempt cessation should be provided at least brief interventions designed to increase their motivation to stop tobacco use.152 Delineated in the current USPHS guideline for the treatment of tobacco use and dependence are 5 brief strategies of intervention that can be provided by any clinician; these strategies consist of asking patients if they use tobacco, advising those who use tobacco to quit, assessing their willingness to quit, assisting those who attempt to quit, and arranging follow-up to prevent relapse.152 Also included in the USPHS guideline are recommendations for the use of pharmacotherapy in general, first-line drugs (i.e., extended-release bupropion, buccal [gum or lozenge] nicotine polacrilex, transdermal nicotine, nicotine nasal spray, nicotine oral inhaler, varenicline) that should be considered initially as part of treatment for tobacco dependence, unless contraindicated, and second-line drugs (i.e., clonidine, nortriptyline).152 Clinicians should encourage all patients attempting to quit smoking to use effective pharmacotherapy, except when contraindicated or in specific populations for which there is insufficient evidence of efficacy (e.g., pregnant women, smokeless tobacco users, light smokers [e.g., <10 cigarettes daily], adolescents).152

Bupropion hydrochloride (extended-release) may be particularly useful in patients greatly concerned about gaining weight after cessation of smoking since therapy with the drug has been shown to result in a delay in such weight gain.152 Nicotine dependence therapy with an antidepressant such as bupropion also may be particularly useful when a depressive disorder is included in the current or past history of patients attempting to quit smoking. 152 Although it is not necessary to assess for possible comorbid psychiatric disorders prior to initiating therapy for nicotine dependence,152 awareness of such comorbidity is important in the assessment and treatment of nicotine-dependent patients since psychiatric disorders are common in this population and smoking cessation or nicotine withdrawal may exacerbate the comorbid condition; bupropion and varenicline therapy also have been associated with worsening of preexisting psychiatric disorders in some cases, and patients with psychiatric comorbidities have an increased risk for relapse to smoking after a cessation attempt.1,152,142,143,168,186

It should be considered that serious neuropsychiatric adverse effects (including but not limited to depression, suicidal ideation, suicide attempt, and completed suicide) have been reported during postmarketing experience in patients being treated with bupropion or varenicline (another smoking cessation drug).1,152,142,143,168,186 The possible risk of serious adverse effects during bupropion therapy should always be weighed against the significant health benefits of its use for smoking cessation, including a reduction in the risk of developing pulmonary disease, cardiovascular disease, and cancer.152

Patients should begin receiving bupropion while they are still smoking since steady-state plasma concentrations of the drug are not achieved until after about 1 week.143,145 A date on which patients quit smoking (cessation date) should be scheduled within the first 2 weeks of therapy with bupropion and generally should be set for the second week (e.g., day 8).143,145 Counseling and support are important interventions for patients to receive throughout therapy with bupropion and for a period after its discontinuance.143,145,152 Achievement of cessation of smoking and maintenance of abstinence are more likely with frequent follow-ups and the provision of support by the clinician and other health-care professionals.143,145,146,147 The importance of participation in behavioral therapies, counseling, and/or support services to which bupropion is adjunctive therapy should be discussed with the patient.143,147 The overall program of interventions to enable cessation of smoking should be reviewed by clinicians.143,146,147 The choice of adjunctive therapy (e.g., nicotine replacement, bupropion) should consider factors such as ease of administration, compliance, and potential adverse effects and risks.146

Depression Associated with Bipolar Disorder !!navigator!!

Bupropion has been used for the treatment of bipolar depression† (bipolar disorder, depressive episode).2,77,78,85,86,102 Lithium preferably or lamotrigine alternatively are considered first-line agents by the American Psychiatric Association (APA) for the treatment of acute depressive episode of bipolar disorder, and lamotrigine (if not used initially), bupropion, or paroxetine are considered second-line agents when first-line agents are ineffective or not tolerated.154 If bupropion was effective for the management of an acute depressive episode, including during the continuation phase, then maintenance therapy with the drug should be considered to prevent recurrences of major depressive episodes.154 In a comparative study, bupropion hydrochloride (mean dosage of 358 mg daily) was as effective as desipramine (mean dosage of 140 mg daily) in the management of depression in patients with bipolar disorder.2,85 Hypomania or mania occurred less frequently with bupropion than with desipramine in patients treated for up to 1 year with either drug and concomitant lithium, carbamazepine, or valproate sodium.85

Because bupropion may be less likely than some other antidepressants to cause a switch to mania or rapid cycling in patients with bipolar disorder, many experts consider bupropion a preferred antidepressant for use in combination with a mood-stabilizing agent in patients with severe (nonpsychotic) depression that is unresponsive to therapy with mood-stabilizing agents alone.154,155 However, the possibility that manic attacks may be precipitated in patients with bipolar disorder who receive bupropion still must be considered.1,13,14,44,86,89,142,143,168 To reduce the risk of developing mania, antidepressants should not be used alone in patients with depression associated with bipolar disorder and the lowest effective dosage of the antidepressant should be used for the shortest time necessary. 154,155

Attention Deficit Hyperactivity Disorder (ADHD) !!navigator!!

Bupropion has been used in a limited number of children with attention deficit hyperactivity disorder† (ADHD).2,44,79,80,134,156,157,158 Although stimulants (e.g., methylphenidate, dextroamphetamine) usually are considered the drugs of first choice when pharmacotherapy is indicated as an adjunct to psychological, educational, social, and other remedial measures in the treatment of ADHD in children,156,157 some clinicians recommend use of bupropion or tricyclic antidepressants as second-line therapy when there has been no response to at least 2 stimulants or when the patient is intolerant of stimulants.156,158 In controlled studies, bupropion was more effective than placebo2 and comparably effective to methylphenidate.2,79 In addition, in a comparative study, bupropion hydrochloride (mean dosage of 3.3 mg/kg daily; range: 1.4-5.7 mg/kg daily) was comparably effective to methylphenidate hydrochloride (mean dosage of 31 mg daily; range: 20-60 mg daily) in overall improvement of symptoms, as evaluated with the Iowa-Conners Abbreviated Parent and Teacher Questionnaire, although a trend favoring methylphenidate was noted in almost all rating scales.2,79

Bupropion also has been used in a limited number of adults with ADHD.2,44,76,126,228 In an uncontrolled study in adults, bupropion hydrochloride (mean dosage of 359 mg daily; range: 150-450 mg daily) administered for 6-8 weeks reduced the severity of signs and symptoms of ADHD, as evaluated with the Targeted Attention Deficit Disorder Symptoms Scale.2,76 Additional study and experience are needed to establish the role of antidepressants versus CNS stimulants in the treatment of this disorder.2,44,76,126,228

Panic Disorder !!navigator!!

Bupropion does not appear to be effective in the treatment of panic disorder and concomitant phobic disorder†.2,44,99,134 However, the drug generally improves symptoms of panic and depression in patients with major depression who have superimposed panic symptoms.44

Dosage and Administration ⬆ ⬇

[Section Outline]

General !!navigator!!

Pretreatment Screening

Patient Monitoring

Administration !!navigator!!

Bupropion is administered orally with or without food.1,142,143,168,226,227 Do not chew, divide, or crush conventional tablets or extended-release tablets; tablets should be swallowed whole.1,142,143,168,226,227

As conventional tablets, bupropion hydrochloride initially is administered orally twice daily in the morning and evening, then increased to 3 times daily, with ≥6 hours separating doses.1,23,24,141 Dosages ≥300 mg should be administered as divided doses of ≤150 mg.1

As extended-release, film-coated tablets (e.g., Wellbutrin® SR), bupropion hydrochloride initially is administered orally once daily in the morning, then increased to twice daily, in the morning and evening.142,143 Dosages >150 mg should be administered as divided doses twice daily, with ≥8 hours separating the doses.142,143

Avoiding bedtime administration of the evening dose of bupropion hydrochloride conventional tablets or extended-release, film-coated tablets may lessen the occurrence of insomnia.1,142,143

As extended-release tablets (Aplenzin®, Wellbutrin® XL), bupropion is administered orally once daily in the morning.168,227 The shell of the extended-release tablet (Aplenzin®, Wellbutrin® XL) does not dissolve and may be passed in the stool.168,227

As extended-release, 450-mg tablets (Forfivo XL®), bupropion hydrochloride is administered once daily.226 If insomnia occurs, avoid administration close to bedtime.226

Dosage !!navigator!!

Dosage of bupropion hydrobromide and bupropion hydrochloride is expressed in terms of the salt.1,142,143,168,226,227 Bupropion hydrobromide doses of 174, 348, or 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, or 450 mg, respectively.227

Major Depression

Increase bupropion dosage gradually and avoid exceeding recommended maximum individual doses or daily dosages to minimize the risk of seizures.1,142,168,227

For the management of depressive disorder in adults, the recommended initial dosage of bupropion hydrochloride as conventional tablets is 100 mg twice daily.1 Alternatively, dosage also has been initiated at 75 mg 3 times daily.23,24,141 To minimize the risk of seizures, bupropion hydrochloride dosage as conventional tablets should not be increased by >100 mg daily every 3 days.1,23,24 After 3 days of dosing, dosage may be increased to 100 mg 3 times daily as conventional tablets.1,23,24,141 Bupropion hydrochloride dosages >300 mg daily can be achieved using the 75- or 100-mg tablets to avoid any individual doses of >150 mg and should not be considered until several weeks of therapy at 300 mg daily have been completed.1 Beyond this time, if no clinical improvement is apparent, dosage of the conventional preparation may be increased to a maximum of 450 mg daily as divided doses ≤150 mg each.1

If extended-release, film-coated tablets of bupropion hydrochloride (e.g., Wellbutrin® SR) are used for the management of depression in adults, the recommended initial dosage is 150 mg once daily given as a single dose.142 If the initial dosage is tolerated adequately, it may be increased to the target dosage of 150 mg twice daily (with ≥8 hours between doses) as early as the fourth day of therapy.142 Caution is recommended when increasing dosages to minimize the risk of bupropion-induced seizures.142 For patients not exhibiting clinical improvement after several weeks of treatment with 300 mg daily, dosage of the extended-release, film-coated tablets may be increased to a maximum of 400 mg daily, given as divided doses of 200 mg twice daily (with ≥8 hours between doses).142 To avoid high peak concentrations of bupropion and/or its metabolites, do not exceed 200 mg in any single dose.142

Alternatively, for management of depression in adults, extended-release tablets of bupropion hydrochloride (Wellbutrin® XL) may be used.168 The recommended initial adult dosage of Wellbutrin® XL extended-release tablets is 150 mg given as a single dose once daily in the morning.168 If the initial dosage is tolerated adequately, the dosage may be increased after 4 days of therapy to the target dosage of 300 mg once daily given as a single dose.168

If therapy is to be switched from conventional bupropion hydrochloride (e.g., Wellbutrin®) or from the extended-release, film-coated tablets (e.g., Wellbutrin® SR) to the once-daily Wellbutrin® XL extended-release tablets, the same total daily dosage should be given when possible, but as a single daily dose.168

Bupropion hydrochloride extended-release 450-mg tablets (Forfivo XL®) may be used for the management of depression in adults but are not appropriate as initial treatment.226 In patients receiving 300 mg daily of another bupropion hydrochloride formulation for ≥2 weeks who require a dosage of 450 mg daily, or in patients currently receiving 450 mg daily of another bupropion hydrochloride formulation, Forfivo XL® may be administered as 450 mg once daily.226 When discontinuing therapy with Forfivo XL®, use another bupropion formulation to taper the dose prior to discontinuance of bupropion.226

Bupropion hydrobromide extended-release tablets (Aplenzin®) also may be used for the management of depression in adults.227 The recommended initial adult dosage of Aplenzin® extended-release tablets is 174 mg once daily in the morning.227 After 4 days of dosing, the dosage may increased to the target dosage of 348 mg once daily in the morning.227 When discontinuing therapy in patients receiving bupropion hydrobromide 348 mg once daily, taper dosage to 174 mg once daily prior to discontinuance.227

Although the optimum duration of bupropion therapy has not been established, acute depressive episodes are thought to require several months or longer of sustained antidepressant therapy.1,142,168,226,227 In addition, some clinicians recommend that long-term antidepressant therapy be considered in certain patients at risk for recurrence of depressive episodes (such as those with highly recurrent unipolar depression).160 Whether the dosage of bupropion required to induce remission is identical to the dosage needed to maintain and/or sustain euthymia is unknown.1,142,168,226,227 Systematic evaluation of bupropion hydrochloride extended-release, film-coated tablets (Wellbutrin® SR) has shown that antidepressant efficacy is maintained for periods of up to 44 weeks in patients receiving 150 mg twice daily.142 Efficacy of bupropion hydrochloride conventional tablets beyond 6 weeks has not been established systematically in controlled studies.1 The usefulness and dosage of the drug in patients receiving prolonged therapy with conventional or extended-release tablets should be reevaluated periodically.1,142,168,226,227

Seasonal Affective Disorder

For the prevention of seasonal major depressive episodes associated with seasonal affective disorder in adults, therapy with extended-release tablets of bupropion hydrochloride (Wellbutrin® XL) or bupropion hydrobromide (Aplenzin®) generally should be initiated in the autumn prior to the onset of depressive symptoms; treatment should continue through the winter season and should be tapered and discontinued in the early spring.168,169,227 The timing of initiation and duration of treatment should be individualized based on the patient's historical pattern of seasonal major depressive episodes.168,227

The recommended initial adult dosage of bupropion hydrochloride, as extended-release tablets (Wellbutrin® XL), is 150 mg once daily in the morning.168 If the 150-mg once-daily dosage is adequately tolerated, the dosage may be increased to the target dosage of 300 mg once daily after 7 days of dosing.168 For patients receiving 300 mg of bupropion hydrochloride as extended-release tablets once daily during the autumn-winter season, the dosage should be tapered to 150 mg once daily prior to discontinuance.168 Dosages >300 mg daily as extended-release bupropion hydrochloride tablets have not been studied for prevention of episodes of seasonal major depression.168,227

The recommended initial adult dosage of bupropion hydrobromide, as extended-release tablets (Aplenzin®), is 174 mg once daily.227 After 7 days of dosing, the dosage may be increased to the target dosage of 348 mg once daily in the morning.227 For patients receiving 348 mg of bupropion hydrobromide as extended-release tablets once daily during the autumn-winter season, the dosage should be tapered to 174 mg once daily prior to discontinuance.227

Smoking Cessation

For use in adults as an adjunct in smoking cessation, the initial dosage of bupropion hydrochloride, as extended-release (SR) tablets is 150 mg daily for the first 3 days of therapy.143,145 The dosage subsequently is increased in most patients to the usual recommended dosage of 150 mg twice daily (with ≥8 hours between doses), which also is the maximum recommended dosage.143,145 Dosages >300 mg daily should not be used for smoking cessation because of the risk of seizures.143 Because steady-state plasma concentrations of the drug are not achieved for about 1 week, bupropion therapy for smoking cessation should be initiated 1-2 weeks prior to discontinuance of cigarette smoking.143,145 Patients should continue to receive bupropion hydrochloride for 7-12 weeks; the need for more prolonged therapy should be individualized depending on benefits and risks to the patient.143,152

For some patients, it may be appropriate to continue pharmacotherapy with bupropion for smoking cessation for periods longer than usually recommended since nicotine dependence is a chronic condition.143 Use of bupropion hydrochloride as an adjunct in smoking cessation has been studied systematically as maintenance therapy at 150 mg twice daily for up to 6 months.143 The decision to continue therapy beyond 12 weeks for smoking cessation must be individualized.143 Although weaning should be encouraged for all smoking cessation pharmacotherapies, continued use of such therapy is clearly preferable to a return to smoking with respect to health consequences.152

Patients have received the combination of bupropion hydrochloride, as extended-release tablets, and transdermal nicotine.143 Patients treated with this combination have been started on bupropion hydrochloride at a dosage of 150 mg daily, while they were still smoking.143 After 3 days, the dosage of bupropion hydrochloride was increased to 150 mg twice daily.143 Patients received concomitant transdermal nicotine therapy at a dosage of 21 mg/24 hours after about 1 week of therapy with bupropion, when the date scheduled for patients to stop smoking was reached.143 The dosage of transdermal nicotine was tapered to 14 and 7 mg/24 hours during the eighth and ninth weeks of therapy, respectively.143

Complete smoking abstinence is the goal of therapy with bupropion hydrochloride.143 Cessation of smoking is unlikely in patients who do not show substantial progress toward abstinence after receiving bupropion hydrochloride for 7 weeks, so such therapy probably should be discontinued at that time in these patients.143 Unsuccessful patients may benefit from interventions to enhance the possibility for success on the next attempt.143 Such patients should be evaluated to determine why failure occurred,143 and another attempt to quit smoking should be encouraged by a more favorable context that includes elimination or reduction of the factors responsible for failure.143

Depression Associated With Bipolar Disorder†

While comparative efficacy of various dosages in the usual range have not been established in the management of depression associated with bipolar disorder†, some experts recommend that dosages of antidepressants, including bupropion, be titrated to levels comparable to those used in the treatment of unipolar depression.155 In clinical studies in patients with depression associated with bipolar disorder, bupropion hydrochloride has been given in a dosage of 75-400 mg daily in conjunction with a mood-stabilizing agent (e.g., carbamazepine, lithium, valproate).2 Antidepressants should be used in these patients for the shortest time necessary.152

ADHD†

For the treatment of attention deficit hyperactivity disorder† (ADHD) in adults, bupropion hydrochloride therapy has been initiated with a dosage of 150 mg daily as conventional tablets.2 Dosage was then titrated to a maximum daily dosage of 450 mg as conventional tablets.2 Bupropion hydrochloride as extended-release tablets also has been used at dosages of 150-450 mg daily.228

Although safety and efficacy of bupropion hydrochloride in pediatric patients <18 years of age have not been established, if bupropion is used for the treatment of ADHD in children†, some experts recommend that those weighing ≥20 kg or more receive an initial dosage of 1 mg/kg daily in 2-3 divided doses. 156 This initial dosage should be given for the first 3 days of therapy, then dosage should be titrated up to 3 mg/kg daily in 2-3 divided doses by day 7 and up to 6 mg/kg daily in 2-3 divided doses or 300 mg (whichever is smaller) by the third week of therapy.156 Alternatively, some experts suggest that pediatric patients with ADHD receive bupropion hydrochloride beginning with an initial dosage of 37.5 mg or 50 mg twice daily with dosage titration over 2 weeks up to a maximum dosage of 250 mg daily (300-400 mg daily in adolescents).157 Up to 4 weeks of bupropion therapy may be necessary to attain maximum effects of the drug.156 Pediatric dosage for ADHD generally has ranged from 50-100 mg 3 times daily.158 If extended-release tablets are used for ADHD, the pediatric dosage generally has ranged from 100-150 mg twice daily.158

Special Populations !!navigator!!

Hepatic Impairment

Because substantial increases in peak plasma bupropion concentrations and accumulation of the drug may occur in patients with moderate or severe hepatic impairment (Child-Pugh score: 7-15), bupropion should be used with caution in these patients.1,142,143,168 Dosage of the drug in these patients should not exceed 75 mg once daily as conventional bupropion hydrochloride tablets, 100 mg once daily or 150 mg every other day as extended-release, film-coated bupropion hydrochloride tablets (e.g., Wellbutrin® SR), 150 mg every other day as Wellbutrin® XL extended-release bupropion hydrochloride tablets or extended-release (SR) bupropion hydrochloride tablets, or 174 mg every other day as extended-release bupropion hydrobromide tablets (Aplenzin®).1,142,143,168,227 The drug should also be used with caution in patients with mild hepatic impairment (Child-Pugh score: 5-6) and a reduction in dose and/or frequency of administration of bupropion should be considered in these patients.1,142,143,168,227

Bupropion hydrochloride extended-release 450-mg tablets (Forfivo XL®) are not recommended for use in patients with hepatic impairment.226

Renal Impairment

Bupropion should be used with caution in patients with renal impairment (creatinine clearance <90 mL/minute), and a reduction in dosage and/or frequency of administration should be considered.1,142,143,168,177,227 Although bupropion is extensively metabolized in the liver to active metabolites, its active metabolites are renally excreted and may accumulate to a greater extent in patients with renal impairment than in those with normal renal function.1,142,143,168,177 Therefore, patients with renal impairment should be closely monitored for possible adverse effects (e.g., seizures) that could indicate higher than recommended drug or metabolite concentration and necessitate a reduction in dose and/or frequency of administration of bupropion.1,142,143,168,177 Based on limited pharmacokinetic data obtained in a single-dose study, some clinicians suggest that patients undergoing hemodialysis should receive 150 mg of bupropion hydrochloride as extended-release tablets every 3 days instead of daily for smoking cessation; a multiple-dose study is needed to confirm these findings.177

Bupropion hydrochloride extended-release 450-mg tablets (Forfivo XL®) are not recommended for use in patients with renal impairment.226

Cautions ⬆ ⬇

[Section Outline]

Contraindications !!navigator!!

Warnings/Precautions !!navigator!!

Warnings

Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults

Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants.1,142,143,161,162,167,168,181,226,227 This risk may persist until clinically important remission occurs.1,142,143,161,168,226,227 Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.1,142,143,161,162,167,168,226,227 However, there has been a long-standing concern 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.1,142,143,161,168,226,227 A boxed warning about the risk of suicidal thoughts and behaviors is included in the prescribing information for bupropion.1,142,143,168,226,227

Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors [SSRIs] and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders.1,142,143,161,162,168,226,227 An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults >24 years of age, and a reduced risk was observed in adults ≥65 years of age.1,142,143,161,162,168,226,227 It is currently 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 major depressive disorder that antidepressants can delay the recurrence of depression.1,142,143,161,162,168,226,227

The risk of suicidality for these drugs was identified in a pooled analysis of data from a total of 24 short-term (4-16 weeks), placebo-controlled studies of 9 antidepressants (i.e., bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, venlafaxine) in >4400 children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders.1,142,143,161,162,168,226,227 The analysis revealed a greater risk of adverse events representing suicidal behavior or thinking (suicidality) during the first few months of treatment in pediatric patients receiving antidepressants than in those receiving placebo.161,162 However, a later meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.181 No suicides occurred in these pediatric trials.1,142,143,161,162,168,181,226,227 There were suicides reported in the adult trials; however, the number was not sufficient to reach any conclusion about drug effect on suicide.1,142,143,168,226,227

The risk of suicidality in FDA's pooled analysis differed across the different psychiatric indications, with the highest incidence observed in the major depressive disorder studies.1,142,143,161,162,168,226,227 In addition, although there was considerable variation in risk among the antidepressants, a tendency toward an increase in suicidality risk in younger patients was found for almost all drugs studied.1,142,143,161,162,168,226,227

FDA recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.1,142,143,161,162,167,168,226,227 Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior, as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider.1,142,143,161,167,168,226,227

Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania 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.1,142,143,161,167,168,226,227 Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms.1,142,143,161,168,226,227 FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.1,142,143,161,168,226,227

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions (e.g., pruritus, urticaria, angioedema, dyspnea) have been reported that may require medical treatment;1,142,143,168,226,227 however, causality has not been established.145 Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.1,142,143,168,226,227

Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity reported.1,142,143,168,226,227

Advise patients to discontinue bupropion and contact their clinician if symptoms of a possible hypersensitivity reaction occur.1,142,143,168,226,227

Other Warnings and Precautions

Neuropsychiatric Symptoms and Suicidality in Smoking Cessation Treatment

Serious neuropsychiatric symptoms, including mood changes (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, have been reported in patients receiving bupropion or varenicline for smoking cessation; such events have occurred in patients with or without psychiatric history.1,142,143,168,186,187,226,227 Some patients with preexisting psychiatric conditions have experienced worsening of their psychiatric illnesses while receiving bupropion for smoking cessation.1,142,143,168,226,227 Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood.1,142,143,168,226,227 Depression, including suicidal ideation in rare cases, has been reported in smokers undergoing a smoking cessation attempt without medication.1,142,143,168,226,227 However, some of these adverse events have been observed in patients receiving bupropion who continued to smoke.1,142,143,168,226,227

Additional analyses and studies, including a large randomized controlled study in >8000 patients, indicate that risk is lower than previously thought and comparable to nicotine replacement therapy or placebo.224,225 However, there is evidence indicating patients with a preexisting psychiatric illness (e.g., depression, anxiety disorder, schizophrenia) may be more likely to experience such events.143,224

Although risk remains, particularly in individuals with current or past psychiatric illnesses, patients generally do not experience serious consequences (e.g., hospitalization); therefore, benefits of smoking cessation (e.g., reduced risk of developing pulmonary disease, cardiovascular disease, and cancer) continue to outweigh risks of these cessation drugs.224

Monitor patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions.1,142,143,168,226,227 Advise patients to discontinue bupropion and contact their clinician immediately if they develop agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient or suicidal ideation/suicidal behavior.1,142,143,168,226,227 The clinician should evaluate the severity of the adverse events and the extent to which the patient is responding to treatment and should consider options, including continued treatment under closer monitoring or discontinuance of treatment.143,168,226,227 In many postmarketing cases, resolution of symptoms after discontinuance of bupropion was reported; however, symptoms persisted in some cases.143,168,226,227 Provide ongoing monitoring and supportive care until symptoms resolve.1,142,143,168,186,226,227

Seizures

Bupropion is associated with a dose-related increase in the risk of seizures.1,6,19,20,24,52,142,143,168,226,227 To reduce the risk of seizures, dosage of bupropion should be increased gradually, and the recommended daily and single dosage recommendations should not be exceeded.1,142,143,168,226,227 The daily dosage of bupropion hydrochloride as conventional tablets should not exceed 450 mg (as 150 mg 3 times daily).1 The dosage of bupropion hydrochloride extended-release, film-coated tablets (e.g., Wellbutrin® SR) should not exceed 400 mg daily (as 200 mg twice daily).142 The dosage of bupropion hydrochloride extended-release (SR) tablets for smoking cessation should not exceed 300 mg daily (as 150 mg twice daily).143 The dosage of bupropion hydrochloride extended-release tablets (e.g., Wellbutrin® XL) should not exceed 300 mg once daily.168 The dosage of bupropion hydrochloride extended-release 450-mg tablets (Forfivo XL®) should not exceed 450 mg once daily.226 The dosage of bupropion hydrobromide extended-release tablets (Aplenzin®) should not exceed 522 mg once daily.227

Seizures have been reported in approximately 0.4% of patients receiving dosages not exceeding 450 mg daily of bupropion hydrochloride as conventional tablets.1,2,21,22,23,24,41,42,44,104,131,141,142 The estimated seizure incidence increases almost 10-fold between daily bupropion hydrochloride doses of 450 and 650 mg.1 Seizures reportedly occurred in about 0.1% of patients treated with the extended-release, film-coated tablets of bupropion hydrochloride (as Wellbutrin® SR) at dosages of 100-300 mg daily, and the incidence increased to approximately 0.4% in patients receiving the maximum recommended dosage of 400 mg daily.142,143,168

Bupropion is contraindicated in patients with a seizure disorder, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.1,142,143,168,226,227 Risk factors for seizure also include patient-related factors (e.g., history of severe head trauma, arteriovenous malformation, CNS tumor, CNS infection, severe stroke), clinical situations (excessive use of alcohol, benzodiazepines, sedative hypnotic agents, or opiates; use of anorectics; use of illicit drugs [e.g., cocaine]; abuse or misuse of prescription drugs [e.g., CNS stimulants]; metabolic disorders [e.g., hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia]; diabetes treated with oral hypoglycemics or insulin), and concomitant drugs that lower seizure threshold (e.g., other bupropion-containing drugs, antipsychotics, tricyclic antidepressants, theophylline, systemic corticosteroids).1,8,142,143,168,226,227

If patients experience a seizure during therapy, permanently discontinue bupropion.1,142,143,168,226,227

Hypertension

Hypertension (sometimes severe) has occurred with bupropion therapy either alone or in combination with transdermal nicotine in patients with and without preexisting hypertension.1,142,143,168,226,227 The risk of hypertension is increased if bupropion is used concomitantly with MAO inhibitors (contraindicated) or other dopaminergic or noradrenergic drugs.1,142,143,168,226,227 The risk of hypertension also appears to be increased in patients receiving concomitant treatment with transdermal nicotine therapy.1,142,143,168,226,227

The safety of bupropion therapy in patients with recent history of MI or unstable heart disease has not been established.1,142,143,168,226,227

Assess blood pressure before initiating bupropion and monitor blood pressure periodically during therapy, especially in patients receiving concomitant nicotine replacement therapy.1,142,143,168,226,227

Activation of Mania or Hypomania

Precipitation of manic, mixed, or hypomanic manic episodes may occur in patients receiving bupropion; the risk appears to be increased in patients with bipolar disorder or in patients with risk factors for bipolar disoder.1,142,143,168,226,227

Bupropion is not FDA-labeled for use in treating bipolar depression.1,142,143,168,226,227 Screen patients for a history of bipolar disorder or risk factors for bipolar disorder (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.1,142,161,168,226,227

Psychosis and Other Neuropsychiatric Effects in Patients Treated for Depression

Neuropsychiatric manifestations, including confusion, delusions, hallucinations, psychosis, disturbances in concentration, and paranoia, have been reported in patients receiving bupropion in depression trials.1,142,143,168,226,227 Some of these patients had a diagnosis of bipolar disorder.1,142,143,168,226,227 In some cases, symptoms diminished with dosage reduction or withdrawal of therapy.1,142,143,168,226,227 Similar types of neuropsychiatric manifestations have been reported during postmarketing experience in patients receiving the drug for smoking cessation.143

Advise patients to contact a clinician if adverse neuropsychiatric effects occur.1,142,143 Discontinue bupropion extended-release tablets (e.g., Wellbutrin® XL, Forfivo XL®, Aplenzin®) if such reactions occur.168,226,227

Angle-closure Glaucoma

The pupillary dilation (mydriasis) that occurs following the use of many antidepressant agents, including bupropion, may trigger an acute attack of angle-closure glaucoma (narrow-angle glaucoma) in patients with anatomically narrow angles who do not have a patent iridectomy.1,142,143,168,226,227

Laboratory Test Interferences

False-positive results for urine immunoassay screening tests for amphetamines have been reported in patients receiving bupropion and following discontinuance of the drug.1,142,143,168,226,227 Confirmatory tests (e.g., gas chromatography/mass spectrometry) can distinguish bupropion from amphetamines.1,142,143,168,226,227

Specific Populations

Pregnancy

Data from epidemiologic studies, including the international bupropion pregnancy registry (675 first-trimester exposures) and a retrospective cohort study using the United Healthcare database (1213 first-trimester exposures), have not shown an overall increased risk for congenital malformations associated with bupropion.1,142,168,226,227 The pregnancy registry was not designed or powered to evaluate specific defects; however, a possible increase in cardiac malformations was identified.1,142,168,226,227 There also are risks to the mother associated with untreated depression in pregnancy.1,142,168,226,227

When bupropion was administered to pregnant rats during organogenesis at doses up to approximately 11 times the maximum recommended human dose (MRHD) of 400 mg daily, no evidence of fetal malformations was observed.142 When administered to pregnant rabbits during organogenesis at doses greater than and approximately equal to the MRHD, non-dose-related increases in the incidence of fetal malformations, and skeletal variations, were observed; decreased fetal weights were observed at doses ≥2 times the MRHD.1,142,168,226,227

The National Pregnancy Registry for Antidepressants, an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy, is available at 844-405-6185 or [Web].1,142,168,226,227

Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum.1,142,168,226,227

Pregnant smokers should be encouraged to attempt smoking cessation using educational and behavioral interventions before drug approaches are used.143 Bupropion extended-release (SR) tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.143

Lactation

Bupropion and its metabolites are distributed into human milk.1,2,64,142,143,168,226,227 The effects of bupropion or its metabolites on milk production are not known.1,142,168,226,227

Limited data from postmarketing reports of bupropion use in nursing women have not identified a clear association of adverse reactions in the breast-fed infant.1,142,168,226,227 Postmarketing reports have described seizures in breast-fed infants; however, the relationship of bupropion exposure and these seizures is unclear.1,142,168,226,227

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for bupropion and any potential adverse effects on the breast-fed child from the drug or the underlying maternal condition.1,142,168,226,227

Pediatric Use

Safety and efficacy of bupropion have not been established in children <18 years of age.1,142,143,168,226,227

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).1,142,143,161,162,168,226,227 However, a later meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.181 No suicides occurred in these pediatric trials.1,142,143,161,162,168,181,226,227

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use.161,162,167,168,181,226,227

Bupropion has been used in a limited number of children 7-16 years of age for attention deficit disorder† without unusual adverse effect.2,44,79,80,134,158

Geriatric Use

Of the approximately 6000 patients studied in clinical trials of extended-release bupropion hydrochloride for smoking cessation or depression, 275 were ≥65 years of age, while 47 were ≥75 years of age.1,142,143,168,226,227 In addition, several hundred patients ≥65 years of age participated in clinical studies using conventional bupropion hydrochloride tablets for depression.1,142,143,168,226,227 Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.1,142,143,168,226,227 In general, smoking cessation interventions that have been shown to be effective in the general population also have been shown to be effective in adults ≥50 years of age.152

The risk of adverse reactions may be increased in patients with impaired renal function.1,142,143,168,226 The possibility of decreased renal function in geriatric patients should be considered in dose selection; consider monitoring renal function in geriatric patients.1,142,143,168,226,227

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.1,142,143,161,162,168,226,227

Hepatic Impairment

Dosage reduction is required in patients with severe hepatic impairment (Child-Pugh score: 7-15).1,142,143,168,227 In patients with mild hepatic impairment (Child-Pugh score: 5-6), consider reducing the frequency of administration and/or dosage.1,142,143,168,227

Use of bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL®) is not recommended in patients with hepatic impairment.226

Renal Impairment

Use bupropion with caution in patients with renal impairment; the drug and its active metabolites may accumulate.1,142,143,168,177,227 Monitor closely for adverse effects that could indicate high bupropion or metabolite exposures; consider a reduction in dosage and/or frequency of administration in patients with renal impairment (glomerular filtration rate <90 mL/minute).1,142,143,168,177,227

Use of bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL®) is not recommended in patients with renal impairment.226

Common Adverse Effects !!navigator!!

Adverse effects reported in ≥5% of patients receiving conventional bupropion hydrochloride tablets include agitation, dry mouth, constipation, headache/migraine, nausea/vomiting, dizziness, excessive sweating, tremor, insomnia, blurred vision, tachycardia, confusion, rash, hostility, cardiac arrhythmias, and auditory disturbance.1

Adverse effects reported in ≥5% of patients receiving bupropion hydrochloride extended-release, film-coated tablets (e.g., Wellbutrin® SR) include headache, dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, abdominal pain, tinnitus, tremor, palpitation, myalgia, sweating, rash, and anorexia.142

Adverse effects reported in ≥5% of patients receiving bupropion hydrochloride extended-release (SR) tablets for smoking cessation include insomnia, rhinitis, dry mouth, dizziness, nervous disturbance, anxiety, nausea, constipation, and arthralgia.143

Adverse effects reported in ≥5% of patients receiving bupropion hydrochloride extended-release tablets (e.g., Wellbutrin® XL, Forfivo XL® ) include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash.168,226

Adverse effects reported in ≥5% of patients receiving bupropion hydrobromide extended-release tablets (e.g., Aplenzin®) include dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, and rash.227

Drug Interactions ⬆ ⬇

[Section Outline]

Bupropion is metabolized to hydroxybupropion, principally by cytochrome P-450 (CYP) isoenzyme 2B6; CYP isoenzymes are not involved in the formation of other bupropion metabolites.1,142,143,168,226,227

Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) inhibit CYP2D6.1,142,143,168,226,227

Drugs Affecting Hepatic Microsomal Enzymes !!navigator!!

Concomitant use of bupropion with CYP2B6 inducers or inhibitors may result in altered serum concentrations of bupropion.1,142,143,168,226,227

Drugs Metabolized by Hepatic Microsomal Enzymes !!navigator!!

Concomitant use of bupropion with substrates of CYP2D6 may result in increased plasma concentrations of the CYP2D6 substrate.1,142,143,168,226,227 Caution should be exercised if bupropion and drugs that are metabolized by the CYP2D6 isoenzyme, including certain antidepressants (e.g., nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline, venlafaxine), antipsychotic agents (e.g., haloperidol, risperidone, thioridazine), β-adrenergic blocking agents (e.g., metoprolol), and class IC antiarrhythmic agents (e.g., propafenone, flecainide), are used concomitantly.1,142,143,144,168,226,227 When drugs that are metabolized by CYP2D6 are added to existing bupropion therapy or if bupropion is added to the treatment regimen of a patient already receiving one of these drugs, a reduction in dosages of the drugs that are metabolized by CYP2D6 should be considered, particularly for those with a narrow therapeutic index.1,142,143,168,226,227

In a clinical trial of 15 male subjects who were extensive CYP2D6 metabolizers, bupropion 300 mg daily (150 mg twice a day) followed by a single 50-mg dose of desipramine increased the peak concentration, AUC, and elijmination half-life 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.1,142,143,168,226,227 Concomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.1,142,143,168,226,227

For prodrugs dependent on CYP2D6 for activation (e.g., tamoxifen), concomitant therapy with bupropion may reduce the clinical efficacy of the prodrug.1,142,143,168,226,227 An increase in dosage of the prodrug may be necessary in patients receiving bupropion.1,142,143,168,226,227

Drugs Affecting the Seizure Threshold !!navigator!!

Extreme caution should be observed with concurrent administration of bupropion and drugs (e.g., other antidepressants, other bupropion-containing drugs, antipsychotic agents, theophylline, systemic corticosteroids) or treatment regimens (e.g., abrupt discontinuance of benzodiazepines) that lower the seizure threshold.1,142,143,168,226,227 Therapy should be initiated with low doses and dosage should be increased gradually.1,142,143,168,227

Smoking Cessation !!navigator!!

Smoking, via enzyme induction, can increase the metabolism of some drugs.149,150,151 Therefore, cessation of smoking (with or without adjunctive use of bupropion) may result in decreased enzyme induction and altered metabolism of some drugs (e.g., theophylline, warfarin, insulin); consider dosage adjustment.143

Alcohol !!navigator!!

Adverse neuropsychiatric events or reduced alcohol tolerance have been reported rarely in patients who ingested alcohol during bupropion therapy.1,142,143,168,226,227 Patients receiving the drug should be advised to minimize or avoid alcohol consumption.1,142,143,168,226,227

Antiretroviral Agents !!navigator!!

Concomitant treatment with antiretroviral agents that induce CYP2B6 (e.g., efavirenz, lopinavir, ritonavir) can decrease bupropion and hydroxybupropion exposure.1,142,143,168,226,227 Administration of ritonavir 100 mg twice daily in healthy subjects reduced the AUC and peak concentration of bupropion by 22% and 21%, respectively.1,142,143,168,226,227 Exposures of hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were decreased by 23, 38, and 48%, respectively.1,142,143,168,226,227 Administration of ritonavir 600 mg twice daily in healthy subjects decreased AUC and peak concentration of bupropion by 66% and 62%, respectively.1,142,143,168,226 Exposures of hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were decreased by 78, 50, and 68%, respectively.1,143,168,226,227 Administration of lopinavir 400 mg/ritonavir 100 mg twice daily in healthy subjects decreased bupropion AUC and peak concentration by 57%; the AUC and peak concentration of hydroxybupropion were decreased by 50% and 31%, respectively.1,142,143,168,226,227 Administration of efavirenz 600 mg once daily for 2 weeks in healthy volunteers reduced the AUC and peak concentration of bupropion by approximately 55% and 34%, respectively; the AUC of hydroxybupropion was unchanged, and peak concentration of hydroxybupropion was increased by 50%.1,142,143,168,226,227 An increase in bupropion dosage may be necessary in patients receiving concomitant treatment with antiretroviral agents that induce CYP2B6; however, the maximum recommended dosage of bupropion should not be exceeded.1,142,143,168,226,227

In vitro studies suggest that nelfinavir may inhibit hydroxylation of bupropion.1,142,143,168,226,227

Benzodiazepines !!navigator!!

Concurrent administration of single doses of bupropion and diazepam to healthy individuals did not result in potentiation of the mental impairment induced by diazepam.104 The impairment of performance on the auditory vigilance test observed with diazepam alone was absent with the combination of diazepam and bupropion.104,123,124 Individuals did not feel more drowsy with the combination of diazepam and bupropion than with placebo or bupropion alone but subjective assessment indicated an increase in drowsiness with diazepam alone.104,123,124

Use with extreme caution; initiate therapy with lower dosages of bupropion and increase gradually.1,142,143

Carbamazepine !!navigator!!

Concomitant treatment with carbamazepine may increase metabolism of bupropion.1,138,142,143,168,226,227 An increase in bupropion dosage may be necessary; however, the maximum recommended dosage of bupropion should not be exceeded.1,142,143,168,226,227

Cimetidine !!navigator!!

Concomitant administration of bupropion and cimetidine resulted in 16% increases in the 24-hour area under the combined plasma concentration-time curve (AUC) and 32% increases in combined peak plasma concentration of the erythro- and threo-amino metabolites of bupropion.1,142,143,168,226,227 However, the pharmacokinetics of bupropion and hydroxybupropion were not affected.1,142,143,168,226,227

Digoxin !!navigator!!

Concomitant treatment with bupropion may decrease plasma concentrations of digoxin.1,142,143 Decreased digoxin exposure has been reported following administration of a single oral dose of 0.5-mg digoxin 24 hours after a single oral dose of extended-release 150-mg bupropion hydrochloride in healthy subjects.1,142,143,168,226,227

Monitor plasma concentrations of digoxin in patients receiving concomitant treatment with bupropion.1,142,143,168,226,227

Dopaminergic Drugs !!navigator!!

Adverse CNS effects (e.g., restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, dizziness), presumably related to cumulative dopamine agonist effects, have been reported in patients receiving bupropion concomitantly with amantadine or levodopa.1,2,44,55,142,143,168,226,227 Caution should be exercised if bupropion therapy is used concomitantly with levodopa or amantadine.1,142,143,168,226,227

Monoamine Oxidase Inhibitors !!navigator!!

Concomitant use of bupropion and monoamine oxidase (MAO) inhibitors is associated with an increased risk of hypertensive reactions.1,142,143,168,226,227 In animals, phenelzine enhanced the acute toxicity of bupropion.1,2,142,143,168,226,227

Concomitant administration of bupropion with an MAO inhibitor is contraindicated; ≥14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion.1,142,143,168,226,227 Conversely, ≥14 days should elapse between discontinuance of bupropion and initiation of an MAO inhibitor.1,142,143,168,226,227

Nicotine !!navigator!!

The manufacturer states that patients can receive bupropion concomitantly with transdermal nicotine therapy if indicated for smoking cessation.143 In a clinical study, concurrent use of bupropion extended-release tablets and nicotine transdermal systems resulted in similar plasma concentrations of bupropion and its active metabolites compared with patients receiving only bupropion extended-release tablets.143 However, the manufacturer reported a possible increased risk of hypertension during combined use, and the possibility of treatment-emergent hypertension should be considered when bupropion is used concomitantly with nicotine replacement therapy.143

Phenobarbital !!navigator!!

Concomitant use of bupropion with phenobarbital may increase metabolism of bupropion.1,142,143,168,226,227 An increase in bupropion dosage may be necessary; however, the maximum recommended dosage of bupropion should not be exceeded.1,142,143,168,226,227

Phenytoin !!navigator!!

Concomitant use of bupropion with phenytoin may increase metabolism of bupropion.1,142,143,168,226,227 An increase in bupropion dosage may be necessary; however, the maximum recommended dosage of bupropion should not be exceeded.1,142,143,168,226,227

Platelet-aggregation Inhibitors !!navigator!!

Concomitant use of platelet-aggregation inhibitors that inhibit CYP2B6 (e.g., clopidogrel, ticlopidine) may increase bupropion exposure but decrease hydroxybupropion exposure.1,142,143,168,226,227 Administration of clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily in healthy subjects increased bupropion peak concentration and AUC by 40% and 60%, respectively, for clopidogrel, and by 38% and 85%, respectively, for ticlopidine.1,142,143,168,226,227 The peak concentration and AUC of hydroxybupropion were decreased by 50% and 52%, respectively, by clopidogrel, and 78% and 84%, respectively, by ticlopidine.1,142,143 This effect is thought to be due to inhibition of CYP2B6, which catalyzes hydroxylation of bupropion.1,142,143 Administration of prasugrel, a weak CYP2B6 inhibitor, in healthy subjects increased bupropion peak concentration and AUC by 14% and 18%, respectively, and decreased peak concentration and AUC of hydroxybupropion by 32% and 24%, respectively.1,142,143,168,226,227

Based on clinical response, dosage adjustment of bupropion may be necessary when used concomitantly with these drugs.1,142,143,168,226,227

Reversible MAO Inhibitors !!navigator!!

Administration of bupropion with a reversible MAO inhibitor (e.g., linezolid, IV methylene blue) may increase the risk of hypertensive reactions; therefore, initiation of bupropion is not recommended in patients receiving treatment with a reversible MAO inhibitor.1,142,143,168,226,227 In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacologic interventions, including hospitalization, should be considered.1,142,143,168,226,227

Urgent treatment with linezolid or IV methylene blue may in some cases be necessary in a patient already receiving therapy with bupropion.1,142,143,168,226,227 If acceptable alternatives to linezolid or IV methylene blue treatment are not available and the potential benefits of linezolid or IV methylene blue treatment are thought to outweigh the risks of hypertensive reactions in a particular patient, bupropion should be discontinued promptly, and linezolid or IV methylene blue can then be administered.1,142,143,168,226,227 The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first.1,142,143,168,226,227 Therapy with bupropion may be resumed 24 hours after the last dose of linezolid or IV methylene blue.1,142,143,168,226,227

Serotonin Reuptake Inhibitors and Serotonin/Norepinephrine Reuptake Inhibitors !!navigator!!

In vitro studies suggest that paroxetine, sertraline, norfluoxetine, and fluvoxamine may inhibit hydroxylation of bupropion.1,142,143,168,226,227

Tamoxifen !!navigator!!

Concomitant use of bupropion with tamoxifen may reduce the efficacy of tamoxifen due to decreased metabolism of tamoxifen to its active form.1,142,143,168,226,227 Increased dosage of tamoxifen may be necessary when used concomitantly with bupropion.1,142,143,168,226,227

Warfarin !!navigator!!

Concomitant use of bupropion with warfarin has resulted in altered prothrombin time/international normalized ratio (INR) that has been rarely associated with hemorrhagic or thrombotic complications.1,142,143,168,226,227

Other Information ⬆ ⬇

Description

Bupropion hydrochloride is an aminoketone-derivative antidepressant agent1,43,142 that is chemically unrelated to tricyclic, tetracyclic, or other currently available antidepressants (e.g., selective serotonin-reuptake inhibitors)1,43,142,143 and also is chemically unrelated to nicotine or other agents currently used in the treatment of nicotine dependence.143

The precise mechanism of antidepressant action of bupropion is unclear, although noradrenergic and/or dopaminergic pathways appear to be principally involved.1,2,115,142,168 Bupropion is a relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine; bupropion does not inhibit monoamine oxidase or reuptake of serotonin.1,142,143,168,226,227

The precise mechanism of action responsible for the efficacy of bupropion as an adjunct in the cessation of smoking is unclear, although noradrenergic and/or dopaminergic effects presumably are involved.143,145,146 It has been suggested that CNS effects of dopamine might be involved in the reinforcement properties of addictive drugs and that nicotine withdrawal manifestations may involve the absence of CNS effects of norepinephrine that are mediated by nicotine.145,147 Efficacy of bupropion in smoking cessation does not appear to depend on the presence of underlying depression.145

Bupropion produces less frequent anticholinergic effects, cardiovascular effects, antihistaminic effects, and weight gain compared with tricyclic antidepressants at usual dosages.2,23,44,104,127,128,133

Bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL®) and bupropion hydrobromide extended-release tablets (Aplenzin®) are bioequivalent to bupropion hydrochloride extended-release tablets (e.g., Wellbutrin® XL).226,227 Bupropion hydrobromide doses of 174, 348, or 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, or 450 mg, respectively.227

Bupropion hydrochloride appears to be well absorbed from the GI tract following oral administration.60 The absolute oral bioavailability of bupropion in humans has not been elucidated because a preparation for IV administration is not available.1,61,143 However, the relative proportion of an oral dose reaching systemic circulation unchanged appears likely to be small.1 In animals, the oral bioavailability of bupropion varies from 5-20%.1,60,143 Food does not appear to affect substantially the peak plasma concentration or area under the plasma concentration-time curve of bupropion achieved with extended-release tablets of the drug.142,143,226

Peak plasma bupropion concentrations usually occur within 2, 3, or 5 hours after oral administration of conventional or extended-release bupropion hydrochloride tablets of Wellbutrin® SR or Wellbutrin® XL, respectively.1,59,61,90,130,142,168 Peak plasma concentrations occur within approximately 5 or 12 hours under fasted or fed conditions, respectively, after oral administration of extended-release, 450-mg bupropion hydrochloride tablets (Forfivo XL®).226 Peak plasma concentrations occur within approximately 5 hours after oral administration of extended-release bupropion hydrobromide tablets (Aplenzin®).227 Steady-state plasma concentrations of bupropion are achieved within 8 days.1,142 Bupropion and its metabolites are distributed into milk.1,2,64 Bupropion is 84% bound to human albumin at in vitro plasma concentrations ≤200 mcg/mL.1,142,143,168,226,227 The half-life of bupropion in the terminal phase averages about 14 hours following single doses;57,61,90,130,139,226 with multiple dosing, the elimination half-life reportedly averages 21 hours.1,139,142 Bupropion is extensively metabolized in the liver1,57,60,61,130,142,143 to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion.1,142,143,168 CYP isoenzymes are not involved in the formation of the threohydrobupropion and erythrohydrobupropion metabolites.1,142 Approximately 87 and 10% of an orally administered, radiolabeled dose of bupropion are excreted in urine and feces, respectively.1,61,130,142,143 Unchanged drug comprises 0.5% of the dose excreted.1,60,61,142,143 Hepatic impairment can decrease elimination of the drug.1,142,143,168 Renal impairment may decrease elimination of the major metabolites.1,142,143,168,177

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

buPROPion Hydrobromide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

174 mg

Aplenzin®

Bausch Health US

348 mg

Aplenzin®

Bausch Health US

522 mg

Aplenzin®

Bausch Health US

buPROPion Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

150 mg*

buPROPion Hydrochloride Extended-release Tablets (SR)

Wellbutrin® XL

Bausch Health US

300 mg*

Wellbutrin® XL

Bausch Health US

450 mg

Forfivo XL®

Almatica Pharma

Tablets, extended-release, film-coated

100 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin® SR

GlaxoSmithKline

150 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin® SR

GlaxoSmithKline

200 mg*

buPROPion Hydrochloride Extended-release Tablets

Wellbutrin® SR

GlaxoSmithKline

Tablets, film-coated

75 mg*

buPROPion Hydrochloride Tablets

100 mg*

buPROPion Hydrochloride Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions September 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

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