buPROPion (Monograph)

Brand names: Aplenzin, Forfivo XL, Wellbutrin
Drug class: Antidepressants, Miscellaneous

Medically reviewed by Drugs.com on May 10, 2025. Written by ASHP.

Introduction

Antidepressant and smoking deterrent; aminoketone derivative.^{1 142 143 168 226 227}

Uses for buPROPion

Major Depressive Disorder

Conventional tablets, sustained-release (Wellbutrin SR) tablets, and extended-release (Wellbutrin XL) tablets used for 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}

Guidelines from the American Psychiatric Association (APA) and the Department of Veterans Affairs/Department of Defense state that there is no evidence to suggest superiority of one first-line antidepressant over another.^{160 229} Recommended first-line agents for initial treatment of major depressive disorder include bupropion, mirtazapine, an SSRI, an SNRI, trazodone, vilazodone, or vortioxetine.²²⁹ Select an initial antidepressant for treatment based on the following factors: patient preference; nature of prior response to medication; safety, tolerability, and anticipated adverse effects; concurrent psychiatric and medical conditions; specific properties of the medication; and cost.¹⁶⁰

Seasonal Affective Disorder

Extended-release tablets (Wellbutrin XL, Aplenzin) used for prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder.^{168 169 170 171 227}

Smoking Cessation

Extended-release (SR) 150-mg tablets used as an aid to smoking cessation therapy; may be used in combination with a nicotine transdermal system if necessary.^{143 145 146 147 152}

US Preventive Services Task Force (USPSTF) guideline recommends that clinicians ask all adults about tobacco use and provide behavioral interventions.²³³ Pharmacotherapy is recommended in all nonpregnant adults who use tobacco.²³³ Recommended pharmacotherapy interventions include nicotine replacement therapy (NRT), bupropion hydrochloride SR, and varenicline.²³³ The American Thoracic Society (ATS) recommends varenicline over bupropion for adult patients in whom pharmacotherapy is being initiated.²³⁴ US Public Health Service (USPHS) guideline recommends bupropion SR as one of several first-line drugs that may reliably increase long-term smoking abstinence rates.¹⁵²

Depression Associated with Bipolar Disorder

Has been used for treatment of bipolar depression^{† [off-label]} (bipolar disorder, depressive episode).^{77 78 85 86 102 154}

Legacy guideline from APA considers bupropion one of several second-line agents for use when first-line agents are ineffective or not tolerated.¹⁵⁴ Guidelines from the Department of Veterans Affairs/Department of Defense state there is insufficient evidence to recommend for or against use of antidepressants as monotherapy or to augment treatment with second-generation antipsychotics or mood stabilizers for acute bipolar depression.²³⁵

Panic Disorder

Has been used in the treatment of panic disorder^{† [off-label]}.^{2 44 99 134 239}

APA legacy guidelines state bupropion may be useful for some patients for the treatment of panic disorder, but cannot be recommended first-line given the limited and mixed data regarding its efficacy.²³⁹

Stimulant Use Disorder

Has been used for the treatment of specific types of stimulant use disorder including cocaine-use disorder^{† [off-label]} and amphetamine-type stimulant disorder^{† [off-label]}.²⁴⁰

American Society of Addiction Medicine (ASAM) and American Academy of Addiction Psychiatry (AAAP) state that bupropion may be considered in patients with cocaine-use disorder to promote abstinence from cocaine use.²⁴⁰ Bupropion, with or without naltrexone, may be considered in patients with amphetamine-type stimulant use disorder to promote reduced use of amphetamine-type stimulants.²⁴⁰

Cancer-related fatigue

Has been used for the treatment of cancer-related fatigue^{† [off-label]}.^{241 242}

American Society of Clinical Oncology (ASCO) guidelines recommend against use of antidepressants to manage symptoms of cancer-related fatigue in adults undergoing cancer treatment based on lack of benefit in studies using SSRIs.²⁴¹ However, ASCO states there is interest evaluating other antidepressants with differing mechanisms such as bupropion.²⁴¹

buPROPion Dosage and Administration

General

Pretreatment Screening

• Assess blood pressure before initiating bupropion.^{1 142 143 168 226 227}

• Screen for history of bipolar disorder and risk factors for bipolar disorder (e.g., family history of suicide, bipolar disorder, or depression) prior to initiating therapy.^{1 142 168 226 227}

Patient Monitoring

• Monitor and closely observe for any indication for clinical worsening, suicidality, or unusual changes in behavior, particularly during initial therapy or following any change (increase or decrease) in dosage.^{1 142 143 168 226 227}

• Monitor for serious neuropsychiatric symptoms or worsening of preexisting psychiatric illness.^{1 142 143 168 226 227}

• Monitor blood pressure periodically.^{1 142 143 168 226 227}

• Consider monitoring renal function in geriatric patients.^{1 142 143 168 226 227}

• Closely monitor patients with renal impairment (Cl_cr <90 mL/minute) for adverse reactions that could indicate high exposures of bupropion or its metabolites.^{1 142 143 168 227}

• Monitor for development of seizures.^{1 142 143 168 226 227}

Dispensing and Administration Precautions

• The Institute for Safe Medication Practices (ISMP) includes Wellbutrin SR and Wellbutrin XL, and buPROPion and busPIRone on their List of Confused Drug Names, and recommends using special safeguards to ensure the accuracy of prescriptions for these drugs; these may include strategies such as using both brand and generic names on prescriptions/labels, using tall-man (mixed case) letters, and including the purpose of the medication on prescriptions.²⁴³

Other General Considerations

• Increase dosage gradually to minimize risk of seizure.^{1 142 143 168 227}

• If a patient is being transitioned to bupropion therapy from an MAOI, allow at least 14 days to elapse between discontinuation of the MAOI and initiation of bupropion; conversely, if switching from bupropion to an MAOI, allow at least 14 days to elapse between discontinuation of bupropion therapy and initiation of the MAOI.^{1 142 143 168 226 227}

• When switching patients from bupropion hydrochloride conventional tablets or bupropion hydrochloride sustained-release film-coated tablets (e.g., Wellbutrin SR) to bupropion hydrochloride extended-release tablets (Wellbutrin XL), give the same total daily dose when possible.¹⁶⁸

• Do not initiate treatment with bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL).²²⁶ For initial dosage titration, use another bupropion formulation; 450-mg tablets can be used in patients who are receiving 300 mg per day for at least 2 weeks and require a dosage of 450 mg per day.²²⁶ If a patient is currently treated with another bupropion formulation at 450 mg per day, the patient can be switched to an equivalent dosage of the 450-mg tablets once daily.²²⁶

• When discontinuing treatment of bupropion hydrochloride extended-release tablets (Wellbutrin XL) 300 mg once daily, decrease dosage to 150 mg once daily prior to discontinuation.¹⁶⁸

• When discontinuing treatment with bupropion hydrochloride extended-release, 450-mg tablets (Forfivo XL), use another bupropion formulation for tapering the dosage prior to discontinuation.²²⁶

• When discontinuing treatment with bupropion hydrobromide extended-release tablets (Aplenzin) 348 mg once daily, decrease dosage to 174 mg bupropion hydrobromide once daily prior to discontinuation.(227)

• When used for smoking cessation, bupropion extended-release tablets (SR) may be used with a nicotine transdermal system.¹⁴³

• When used for smoking cessation, patients receiving bupropion extended-release tablets (SR) should be advised of behavioral interventions, counseling services, and other support services to be used to increase likelihood of quitting smoking and remaining abstinent.¹⁴³ If a patient fails an attempt to quit, the patient may benefit from interventions and/or NRT to improve chances for success on subsequent attempts.¹⁴³

Administration

Oral Administration

Administer orally with or without food.^{1 142 143 168 226 227}

Conventional Bupropion Hydrochloride Tablets

Initially, administer orally twice daily in the morning and evening, then increase to 3 times daily, with ≥6 hours separating doses.¹

Dosages ≥300 mg should be administered as divided doses ≤150 mg per dose.¹

Avoid bedtime administration of evening dose to decrease incidence of insomnia.¹

Do not chew, divide, or crush tablets; swallow tablets whole.¹

Extended-release Tablets

Sustained-release (SR), film-coated bupropion hydrochloride tablets (e.g., Wellbutrin SR): Initially, administer orally once daily in the morning, then increase to twice daily, in the morning and evening.¹⁴² Dosages >150 mg should be administered as divided doses twice daily, with ≥8 hours separating the doses.¹⁴² Avoid bedtime administration of evening dose to decrease incidence of insomnia.¹⁴²

Extended-release (SR) bupropion hydrochloride tablets: Administer orally once daily for the first 3 days, then usually increase to twice daily administration with ≥8 hours separating the doses.¹⁴³ Avoid bedtime administration of evening dose to decrease incidence of insomnia.¹⁴³

Extended-release bupropion hydrobromide (Aplenzin) or bupropion hydrochloride (Wellbutrin XL) tablets: Administer orally once daily in the morning.^{168 227}

Extended-release bupropion hydrochloride 450-mg film-coated tablets (Forfivo XL): Administer orally once daily in the morning.²²⁶

Do not chew, divide, or crush extended-release tablets; tablets should be swallowed whole.^{142 143 168 226 227}

The shell of some extended-release tablets (e.g., Aplenzin, Wellbutrin XL) does not dissolve and may be passed in the stool.^{168 227}

Dosage

Available as bupropion hydrochloride or bupropion hydrobromide; dosage expressed in terms of the salt.^{1 142 143 168 226 227}

Bupropion hydrobromide doses of 174, 348, and 522 mg are equivalent to bupropion hydrochloride doses of 150, 300, and 450 mg, respectively.²²⁷

Adults

Major Depression

Optimum duration of treatment not established; however, acute depressive episodes thought to require several months or longer of sustained antidepressant therapy.^{1 142 168 226 227}

Unknown whether dosage required for initial response is identical to dosage needed to maintain response.^{1 142 168 226 227}

Periodically reevaluate usefulness and appropriate dosage of drug in patients receiving prolonged therapy with conventional, SR, or extended-release tablets.^{1 142 168 226 227}

Therapy with Conventional Bupropion Hydrochloride Tablets

Initially, 100 mg twice daily.¹

To minimize risk of seizures, do not increase dosage by >100 mg daily every 3 days.¹

If clinical improvement not apparent after >3 days, may increase to 100 mg 3 times daily.¹

Dosages >300 mg should not be considered until completion of several weeks of therapy; if no improvement is apparent, then the dosage may be increased to a maximum of 150 mg 3 times daily.¹

Therapy with Sustained-release and Extended-release Bupropion Hydrochloride Tablets

Sustained-release, film-coated tablets (e.g., Wellbutrin SR): Initially, 150 mg once daily in the morning.¹⁴² If tolerated, may increase to target dosage of 150 mg twice daily (with ≥8 hours between doses) as early as day 4 of therapy.¹⁴² Dosages >300 mg daily should not be considered until completion of several weeks of therapy; then, if no apparent improvement, may increase dosage to maximum of 200 mg twice daily (with ≥8 hours between doses).¹⁴²

Extended-release tablets (Wellbutrin XL): Initially, 150 mg once daily.¹⁶⁸ If tolerated, may increase to target dosage of 300 mg once daily after 4 days of therapy.¹⁶⁸

Extended-release tablets (Forfivo XL): 450 mg once daily in patients who have received another bupropion hydrochloride formulation at a dosage of 300 mg daily for ≥2 weeks and require a dosage of 450 mg daily, or in patients currently receiving bupropion hydrochloride 450 mg daily of another bupropion formulation.²²⁶

Therapy with Extended-release Bupropion Hydrobromide Tablets

Extended-release tablets (e.g., Aplenzin): Initially, 174 mg once daily in the morning.²²⁷ After day 4 of therapy, may increase to target dosage of 348 mg once daily in the morning.²²⁷

Seasonal Affective Disorder

Therapy with Extended-release Bupropion Hydrochloride Tablets

Extended-release tablets (Wellbutrin XL): Initiate therapy in autumn prior to onset of depressive symptoms; continue treatment through the winter and taper and discontinue in early spring.¹⁶⁸ Individualize timing of initiation and duration of therapy based on patient’s historical pattern of seasonal depressive episodes.¹⁶⁸

Initially, 150 mg once daily in the morning.¹⁶⁸ If tolerated, increase dosage after 7 days to target dosage of 300 mg once daily.¹⁶⁸

For patients receiving 300 mg once daily during the autumn-winter period, taper dosage to 150 mg once daily prior to discontinuance.¹⁶⁸

Therapy with Extended-release Bupropion Hydrobromide Tablets

Extended-release tablets (Aplenzin): Initiate therapy in autumn prior to onset of depressive symptoms; continue treatment through the winter and taper and discontinue in early spring.²²⁷ Individualize timing of initiation and duration of therapy based on patient’s historic pattern of seasonal depressive episodes.²²⁷

Initially, 174 mg once daily.²²⁷ After 7 days of dosing, may increase to target dose of 348 mg once daily in the morning.²²⁷

For patients receiving 348 mg once daily during the autumn-winter period, taper dosage to 174 mg once daily prior to discontinuance.²²⁷

Smoking Cessation

Therapy with Extended-release (SR) Bupropion Hydrochloride Tablets

Initially, 150 mg daily for the first 3 days of therapy.^{143 145} Initiate 1–2 weeks prior to discontinuance of cigarette smoking.^{143 145}

Maintenance, 150 mg twice daily (with ≥8 hours between doses).^{143 145} Continue therapy for 7–12 weeks; evaluate need for prolonged therapy after that period based on individual patient assessment.¹⁴³

Cessation of smoking is unlikely in patients who do not show substantial progress toward abstinence after 7 weeks of therapy, so such therapy generally should be discontinued at that time in these patients.¹⁴³

Special Populations

Hepatic Impairment

Smoking cessation in patients with severe hepatic cirrhosis: Maximum 150 mg every other day as extended-release (SR) tablets .¹⁴³

Major depression, seasonal affective disorder, or smoking cessation in patients with mild hepatic impairment (Child-Pugh score: 5–6): Reduce dosage and/or frequency of administration as required.^{1 142 143 168 227}

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

Renal Impairment

Active metabolites may accumulate; reduce dosage and/or frequency of administration as required for patients with a Cl_cr < 90 mL/minute.^{1 142 143 168 177 227}

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

Geriatric Patients

Use caution when administering bupropion to geriatric patients; consider dosage reduction and monitor renal function due to age-related decreases in renal function.^{1 142 143 168 226 227}

Cautions for buPROPion

Contraindications

• Seizure disorders.^{1 142 143 168 226 227}

• Current or past diagnosis of anorexia nervosa or bulimia.^{1 142 143 168 226 227}

• Patients receiving any other bupropion formulation because risk of seizures is dose-dependent.²²⁶

• Patients undergoing abrupt discontinuance of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.^{1 142 143 168 226 227}

• Patients currently receiving, or having recently received (i.e., within 14 days), MAOI therapy.^{1 142 143 168 226 227}

• Patients currently receiving a reversible MAOI (e.g., linezolid, IV methylene blue).^{1 142 143 168 226 227}

• Hypersensitivity to the drug or any ingredient in the formulation.^{1 142 143 168 226 227}

Warnings/Precautions

Warnings

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

Increased risk of suicidal thoughts and behavior in adolescent and young adult patients taking antidepressants (See Boxed Warning).^{1 142 143 168 226 227} Depression itself is a risk factor for suicidal thoughts and behaviors.^{1 142 143 168 226 227}

Monitor all patients treated with bupropion for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.^{1 142 143 168 226 227}

Counsel families and caregivers to monitor for changes in the patient's behavior, and to report such symptoms to a clinician. ^{1 142 143 168 226 227} Consider changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidal thoughts or behaviors. .^{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, reported. ^{1 142 143 168 226 227}

Monitor patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions.^{1 142 143 168 226 227} Discontinue bupropion in patients who develop agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient or who develop suicidal ideation or suicidal behavior.^{1 142 143 168 226 227}

Seizures

Dose-related increase in risk of seizures reported;^{1 142 143 168 226 227} increase dose gradually and avoid exceeding recommended daily and single doses.^{1 142 143 168 226 227} Do not exceed a total daily dosage of 450 mg (as 150 mg 3 times daily) of bupropion hydrochloride as conventional tablets;¹ 400 mg daily (as 200 mg twice daily) of bupropion hydrochloride as sustained-release, film-coated tablets (e.g., Wellbutrin SR);¹⁴² 300 mg daily (as 150 mg twice daily) of bupropion hydrochloride as extended-release (SR) tablets for smoking cessation;¹⁴³ 300 mg once daily of bupropion hydrochloride as extended-release tablets (e.g., Wellbutrin XL);¹⁶⁸ 450 mg once daily of bupropion hydrochloride as extended-release, 450-mg tablets (Forfivo XL);²²⁶ or 522 mg once daily of bupropion hydrobromide as extended-release tablets (Aplenzin).²²⁷

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}

If patients experience a seizure during therapy, discontinue medication and do not restart.^{1 142 143 168 226 227}

Hypertension

Hypertension (sometimes severe) has occurred with bupropion therapy.^{1 142 143 168 226 227} Risk of hypertension is increased with concomitant use of MAOIs (contraindicated) or other dopaminergic or noradrenergic drugs; also increased with concomitant transdermal nicotine therapy.^{1 142 143 168 226 227}

Safety in patients with recent history of MI or unstable heart disease not established.^{1 142 143 168 226 227}

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

Activation of Mania or Hypomania

Possible precipitation of manic, mixed, or hypomanic manic episodes; risk appears increased in patients with bipolar disorder or who have risk factors for bipolar disorder.^{1 142 143 168 226 227}

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

Psychosis and Other Neuropsychiatric Effects in Patients Treated for Depression

Neuropsychiatric manifestations, including confusion, delusions, hallucinations, psychosis, disturbances in concentration, and paranoia, 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 reported during postmarketing experience in patients receiving the medication for smoking cessation.¹⁴³

Advise patients to contact a clinician if adverse neuropsychiatric effects occur.^{1 142 143}

Angle-closure Glaucoma

Pupillary dilation (mydriasis) occurs with many antidepressants, including bupropion, and 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}

Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions (e.g., pruritus, urticaria, angioedema, dyspnea) reported.^{1 142 143 168 226 227} Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.^{1 142 143 168 226 227}

Possible arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity.^{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}

Specific Populations

Pregnancy

Data from epidemiologic studies have not shown an overall increased risk for congenital malformations with bupropion.^{1 142 168 226 227} International bupropion pregnancy registry was not designed or powered to evaluate specific defects; however, possible increase in cardiac malformations identified.^{1 142 168 226 227}

National Pregnancy Registry for Antidepressants at 1-844-405-6185 or [Web].^{1 142 168 226 227}

Consider the risks to the female 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}

Encourage pregnant smokers to attempt cessation using educational and behavioral interventions before using medication approaches.¹⁴³ Use bupropion extended-release (SR) tablets during pregnancy only if potential benefit justifies potential risk to the fetus.¹⁴³

Lactation

Distributed into milk.^{1 142 143 168 226 227} Effects of bupropion or its metabolites on milk production not known.^{1 142 168 226 227}

Limited data from postmarketing reports of bupropion use in nursing females have not identified a clear association of adverse reactions in the breast-fed infant.^{1 142 168 226 227} Postmarketing reports of seizures in breast-fed infants; however, causal relationship not established.^{1 142 168 226 227}

Pediatric Use

Safety and efficacy not 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).^{1 142 143 168 226 227} 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.^{1 142 143 168 226 227}

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use. ^{168 226 227}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, possibility of increased sensitivity to the medication in some older patients cannot be ruled out.^{1 2 142 143 168 226 227}

Consider increased possibility of impaired renal function, which may increase risk of adverse effects, when selecting dosage; may be useful to monitor renal function.^{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.^{1 142 143 168 226 227}

Hepatic Impairment

Reduced dosage required in patients with severe hepatic impairment (Child-Pugh score: 7–15).^{1 142 143 168 227} In patients with severe hepatic impairment, maximum plasma concentration increased by 70% and mean half-life increased (29 hours versus 19 hours in healthy patients).^{168 226 227}

In patients with mild hepatic impairment (Child-Pugh score: 5–6), consider reduced dosage and/or frequency.^{1 142 143 168 227}

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

Renal Impairment

Use with caution; parent drug and active metabolites may accumulate.^{1 142 143 168} Monitor closely for adverse effects that could indicate high bupropion or metabolite exposures; consider reduced dosage and/or frequency.^{1 142 143 168} Compared to patients with normal renal function, patients with moderate-to-severe renal impairment (Cl_cr 30.9 +/- 10.8 mL/minute) were found to have about an approximately 2-fold higher exposure to bupropion when administered a single 150 mg dose of SR bupropion.^{1 142 143 168 226 227}

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

Common Adverse Effects

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

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

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

Adverse effects (≥5%) in patients receiving bupropion hydrochloride extended-release tablets (e.g., Wellbutrin XL, Forfivo XL): Dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash.^{168 226}

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

Drug Interactions

Metabolized to hydroxybupropion, principally by CYP2B6; CYP isoenzymes not involved in the formation of other bupropion metabolites.^{1 142 143 168 226 227}

Bupropion and its metabolites inhibit CYP2D6.^{1 142 143 168 226 227}

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered serum concentrations of bupropion) with medications that induce or inhibit CYP2B6.^{1 142 143 168 226 227}

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations).^{1 142 143 168 226 227} Dosage reduction of the CYP2D6 substrate may be necessary, particularly for medications with a narrow therapeutic index.^{1 142 143 168 226 227}

Prodrugs dependent on CYP2D6 for activation (e.g., tamoxifen): Possible reduced clinical efficacy of the prodrug.^{1 142 143 168 226 227} An increase in dosage of the prodrug may be necessary.^{1 142 143 168 226 227}

Drugs Affecting the Seizure Threshold

Use extreme caution with concomitant use of other medications (e.g., other antidepressants, other bupropion-containing drugs, antipsychotic agents, theophylline, systemic corticosteroids) or treatment regimens (e.g., abrupt discontinuation of benzodiazepines) that lower the seizure threshold.^{1 142 143 168 226 227}

Smoking Cessation

Cessation of smoking (with or without adjunctive use of bupropion) may result in decreased enzyme induction and altered metabolism of some medications (e.g., theophylline, warfarin, insulin); consider dosage adjustment.¹⁴³

Specific Drugs

buPROPion Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations usually occur within 2, 3, or 5 hours after oral administration of conventional, sustained-release film-coated (e.g., Wellbutrin SR) or extended-release (Wellbutrin XL) bupropion hydrochloride tablets, respectively.^{1 142 143 168} 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 achieved within 8 days.¹

At steady state, conventional and extended-release tablets (Wellbutrin SR, Wellbutrin XL) are essentially bioequivalent.^{142 168}

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

Food

Food does not appear to substantially affect the peak plasma concentration or extent of absorption achieved with extended-release tablets.^{142 143 168 226}

Distribution

Extent

Bupropion and its metabolites are distributed into milk.^{1 142 143 168 226 227}

Plasma Protein Binding

84% bound to human albumin.^{1 142 143 168 226 227}

Elimination

Metabolism

Extensively metabolized in the liver^{1 142 143 168 226 227} to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion.^{1 142 143 168 226 227} CYP isoenzymes not involved in the formation of threohydrobupropion and erythrohydrobupropion metabolites.^{1 142 168 226 227}

Elimination Route

Excreted in urine (87%) and feces (10%), principally as metabolites.^{1 142 143 168 226 227}

Half-life

The half-life in the terminal phase (t_½β) averages about 21 hours after chronic dosing.^{1 142 168}

Special Populations

Hepatic impairment can decrease elimination of bupropion.^{1 142 143 168 226 227}

Renal impairment may decrease elimination of major metabolites.^{1 142 143 168 226 227}

Stability

Storage

Oral

Conventional Bupropion Hydrochloride Tablets

20–25°C in tight container; protect from light and moisture.¹

Extended-release Bupropion Hydrochloride Tablets

Sustained-release (e.g., Wellbutrin SR): 20–25°C (excursions permitted to 15–30°C); protect from light and moisture.^{142 143}

Extended-release tablets (Wellbutrin XL): 25°C (excursions permitted to 15–30°C).¹⁶⁸

Extended-release 450-mg tablets (Forfivo XL): 20–25°C.²²⁶

Extended-release Bupropion Hydrobromide Tablets

Extended-release tablets (Aplenzin): 25°C (excursions permitted to 15–30°C).²²⁷

Actions

• Chemically unrelated to tricyclic, tetracyclic, or other currently available antidepressants (e.g., SSRIs);^{1 43 142 143 168 226 227} also chemically unrelated to nicotine or other agents currently used in treatment of nicotine dependence.¹⁴³

• Mechanism of antidepressant action is unclear; noradrenergic and/or dopaminergic pathways appear to be principally involved.^{1 2 115 142 168 226 227} Relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine; does not inhibit monoamine oxidase or reuptake of serotonin.^{1 142 143 168 226 227}

• Mechanism of action as an adjunct in the cessation of smoking is unclear; noradrenergic and/or dopaminergic effects presumably are involved.^{143 145 146}

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (medication guide).^{1 142 143 168 226 227}

• Advise patients to swallow tablets whole and not to crush, chew, or divide the tablets.^{1 142 143 168 226 227}

• Advise patients to take conventional bupropion hydrochloride tablets in 3–4 divided doses daily, with ≥6 hours between subsequent doses.¹

• Instruct patients to take bupropion hydrochloride extended-release tablets in two divided doses, preferably with ≥8 hours between successive doses, when doses are >150 mg daily to minimize the risk of seizures.^{142 143}

• Instruct patients to take bupropion hydrochloride extended-release tablets (e.g., Wellbutrin XL) once daily in the morning.¹⁶⁸

• Instruct patients that if they miss a dose, they should not take an extra tablet to make up for the missed dose and should take the next tablet at the regular time because of the dose-related risk of seizure.^{1 142 143 168 226 227}

• Advise patients and caregivers to monitor for the emergence of suicidal thoughts and behaviors, especially during the first few months of therapy or during periods of dosage adjustment.^{1 142 143 168 226 227} Advise families and caregivers of patients to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt; such symptoms should be reported to the patient’s clinician, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.^{1 142 143 168 226 227}

• Inform patients of the risk of serious neuropsychiatric symptoms, including changes in mood (e.g., depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic as well as suicidal ideation, suicide attempt, and completed suicide, when used for smoking cessation.^{1 142 143 168 226 227} Instruct patients to discontinue bupropion and contact a clinician if they experience such symptoms.^{1 142 143 168 226 227}

• Inform patients of the risk of hypersensitivity reactions.^{1 142 143 168 226 227} Advise patients to stop taking bupropion and notify their clinician if they develop signs of a severe allergic reaction.^{1 142 143 168 226 227}

• Inform patients of the risk of seizures.^{1 142 143 168 226 227} Advise patients to permanently stop taking the drug and immediately notify their clinician if they have a seizure.^{1 142 143 168 226 227} Advise patients to minimize or avoid use of alcohol.^{1 142 143 168 226 227}

• Advise patients that bupropion can cause mild pupillary dilation, which can lead to an episode of angle-closure glaucoma in susceptible individuals. ^{1 142 143 168 226 227}

• Advise patients to avoid concomitant therapy with any other preparations containing bupropion.^{1 142 143 168 226 227}

• Advise patients of the potential for impaired ability to perform tasks requiring judgment or motor and cognitive skills.^{1 142 143 168 226 227} Advise patients to avoid operating machinery or driving a motor vehicle until the effects on the individual are known.^{1 142 143 168 226 227} Inform patients that bupropion may decrease alcohol tolerance.^{1 142 143 168 226 227}

• Instruct patients to minimize or avoid consumption of alcohol; excessive use of alcohol or abrupt cessation of use may alter the seizure threshold.^{1 142 143 168 226 227}

• Advise patients that Wellbutrin SR and WellbutrinXL may have an odor.^{142 143 168}

• Advise patients to store conventional bupropion hydrochloride tablets, film-coated sustained-release tablets (e.g., Wellbutrin SR) at room temperature (20–25ºC) and to keep the tablets dry and out of light.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.^{1 142 143 168 226 227}

• Advise females to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 142 143 168 226 227} Advise patients of any pregnancy exposure registry that monitors pregnancy outcomes in females exposed to bupropion during pregnancy.^{1 142 168 226 227} Advise patients that bupropion in distributed into milk in small amounts.¹⁴³

• Advise patients of other important precautionary information.^{1 142 143 168 226 227}

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.

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

Related/similar drugs

Frequently asked questions

• How long does it take Wellbutrin XL/SR (bupropion) to work?
• Does Auvelity work better than Wellbutrin?

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