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

Medically reviewed by Drugs.com on Sep 24, 2023. Written by ASHP.

Introduction

Antidepressant and smoking deterrent; aminoketone derivative.

Uses for buPROPion

Major Depressive Disorder

Treatment of major depressive disorder as defined by the Diagnostic and Statistical Manual (DSM).

May be useful (alone or in combination with other antidepressants) in patients with refractory depression.

Recommended as an option for first-line pharmacologic therapy for most patients with major depressive disorder according to clinical guidelines from the American Psychiatric Association (APA).

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 (SAD).

Smoking Cessation

Extended-release (SR) 150-mg tablets used as an adjunct in the cessation of smoking (alone or in combination with nicotine replacement therapy).

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.

Depression Associated with Bipolar Disorder

Treatment of patients with bipolar depression^{† [off-label]} (bipolar disorder, depressive episode).

APA considers bupropion one of several second-line agents for use when first-line agents are ineffective or not tolerated.

Attention Deficit Hyperactivity Disorder (ADHD)

Used in a limited number of children and adults in the management of ADHD^{† [off-label]}.

Panic Disorder

Ineffective in the treatment of panic disorder and concomitant phobic disorder^{† [off-label]}, but may improve symptoms of panic and depression in patients with major depression who have superimposed panic symptoms.

Related/similar drugs

Vraylar, sertraline, trazodone, Lexapro, Zoloft, citalopram, Wellbutrin

buPROPion Dosage and Administration

General

Pretreatment Screening

• Assess BP before initiating bupropion.

• Screen for history of bipolar disorder and risk factors (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

Patient Monitoring

• Appropriately monitor and closely observe all patients receiving bupropion 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.

• Monitor all patients receiving bupropion for smoking cessation for serious neuropsychiatric symptoms or worsening of preexisting psychiatric illness.

• Monitor BP periodically.

• Consider monitoring renal function in geriatric patients.

• Closely monitor patients with renal impairment (GFR <90 mL/minute) for adverse reactions that could indicate high exposures of bupropion or its metabolites.

Administration

Oral Administration

Administer orally with or without food.

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.

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

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

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

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. Dosages >150 mg should be administered as divided doses twice daily, with ≥8 hours separating the doses. Avoid bedtime administration of evening dose to decrease incidence of insomnia.

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

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

Extended-release bupropion hydrochloride 450-mg film-coated tablets (Forfivo XL): Administer orally once daily. If insomnia occurs, avoid administration close to bedtime.

Do not chew, divide, or crush extended-release tablets; tablets should be swallowed whole.

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

Dosage

Available as bupropion hydrochloride or bupropion hydrobromide; dosage expressed in terms of the salt.

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

Pediatric Patients

ADHD† [off-label]

Bupropion Hydrochloride

Oral

Children weighing ≥20 kg: Initially, 1 mg/kg daily in 2–3 divided doses. After 3 days, titrate up to 3 mg/kg daily in 2–3 divided doses by day 7, then up to 6 mg/kg daily in 2–3 divided doses or 300 mg (whichever is smaller) by third week of therapy.

Alternatively, may give initial dose of 37.5 or 50 mg twice daily with titration over 2 weeks up to a maximum of 250 mg daily (300–400 mg daily in adolescents).

Pediatric dosage for ADHD generally has ranged from 50–100 mg 3 times daily for conventional tablets or 100–150 mg twice daily for extended-release tablets.

Adults

Major Depression

Increase bupropion dosage gradually; avoid exceeding recommended maximum individual doses or daily dosages to minimize risk of seizures.

Optimum duration of treatment not established; however, acute depressive episodes thought to require several months or longer of sustained antidepressant therapy. Some clinicians recommend that long-term antidepressant therapy be considered in certain patients at risk for recurrence of depressive episodes (e.g., those with highly recurrent unipolar depression).

Unknown whether dosage required to induce remission is identical to dosage needed to maintain and/or sustain euthymia.

Antidepressant efficacy of bupropion hydrochloride extended-release, film-coated tablets (Wellbutrin SR) shown to be maintained for periods of up to 44 weeks in patients receiving 150 mg twice daily.

Efficacy of bupropion hydrochloride conventional tablets beyond 6 weeks not established systematically in controlled studies.

Periodically reevaluate usefulness and appropriate dosage of drug in patients receiving prolonged therapy with conventional or extended-release tablets.

Therapy with Conventional Bupropion Hydrochloride Tablets

Oral

Initially, 100 mg twice daily. Alternatively, dosage may be initiated at 75 mg 3 times daily.

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

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

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.

Therapy with Extended-release Bupropion Hydrochloride Tablets

Oral

Extended-release, film-coated tablets (e.g., Wellbutrin SR): Initially, 150 mg once daily in the morning. If tolerated, may increase to target dosage of 150 mg twice daily (with ≥8 hours between doses) as early as fourth day of therapy. 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).

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

When switching from conventional or extended-release, film-coated tablets (e.g., Wellbutrin SR) to extended-release tablets (Wellbutrin XL), administer same total daily dose when possible.

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

When discontinuing therapy with Forfivo XL, use another bupropion formulation to taper the dose prior to discontinuance of bupropion.

Therapy with Extended-release Bupropion Hydrobromide Tablets

Oral

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

When discontinuing therapy in patients receiving 348 mg once daily, taper dosage to 174 mg once daily prior to discontinuance.

Seasonal Affective Disorder

Therapy with Extended-release Bupropion Hydrochloride Tablets

Oral

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. Individualize timing of initiation and duration of therapy based on patient’s historical pattern of seasonal depressive episodes.

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

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

Therapy with Extended-release Bupropion Hydrobromide Tablets

Oral

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. Individualize timing of initiation and duration of therapy based on patient’s historic pattern of seasonal depressive episodes.

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

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

Smoking Cessation

Therapy with Extended-release (SR) Bupropion Hydrochloride Tablets

Oral

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

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

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.

Combination Therapy with Extended-release Bupropion Hydrochloride Tablets and Transdermal Nicotine Patches

Oral

Initially, 150 mg daily, and after 3 days increase to 150 mg twice daily (with ≥8 hours between doses) while still smoking.

After about 1 week of therapy, when the patient is scheduled to stop smoking, initiate transdermal nicotine therapy at a dosage of 21 mg/24 hours.

Taper transdermal nicotine to 14, then to 7 mg/24 hours during the eighth and ninth weeks of therapy, respectively.

Depression Associated With Bipolar Disorder† [off-label]

Bupropion Hydrochloride

Oral

Dosages generally range from 75–400 mg in conjunction with a mood-stabilizing agent (e.g., carbamazepine, lithium, valproate).

ADHD†

Therapy with Conventional Bupropion Hydrochloride Tablets

Oral

Initially, 150 mg daily. May be titrated up to 450 mg daily.

Therapy with Extended-release Bupropion Hydrochloride Tablets

Oral

150–450 mg daily.

Prescribing Limits

Adults

Major Depression

Oral

Conventional bupropion hydrochloride tablets: Maximum 450 mg daily (not >150 mg per dose).

Extended-release, film-coated bupropion hydrochloride tablets (e.g., Wellbutrin SR): Maximum 400 mg daily (not >200 mg per dose).

Extended-release bupropion hydrochloride tablets (Wellbutrin XL): Maximum 300 mg daily.

Extended-release, 450-mg bupropion hydrochloride tablets (Forfivo XL): Maximum 450 mg daily.

Extended-release bupropion hydrobromide tablets (Aplenzin): Maximum 522 mg daily.

Seasonal Affective Disorder

Oral

Extended-release bupropion hydrochloride tablets (e.g., Wellbutrin XL): Dosages >300 mg daily not studied.

Smoking Cessation

Oral

Extended-release (SR) bupropion hydrochloride tablets: 300 mg daily (not >150 mg per dose).

Special Populations

Hepatic Impairment

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

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.

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

Renal Impairment

Active metabolites may accumulate; reduce dosage and/or frequency of administration as required.

Smoking cessation in patients undergoing hemodialysis: Some clinicians recommend a dosage of 150 mg every 3 days as extended-release, film-coated bupropion hydrochloride tablets.

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

Cautions for buPROPion

Contraindications

• Seizure disorders.

• Current or past diagnosis of anorexia nervosa or bulimia.

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

• Patients undergoing abrupt discontinuance of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

• Patients currently receiving, or having recently received (i.e., within 14 days), MAO inhibitor therapy.

• Patients currently receiving a reversible MAO inhibitor (e.g., linezolid, IV methylene blue).

• Hypersensitivity to the drug or any ingredient in the formulation.

Warnings/Precautions

Warnings

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

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving bupropion for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid/anaphylactic reactions (e.g., pruritus, urticaria, angioedema, dyspnea) reported; may require medical treatment. Postmarketing reports include erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock.

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

Advise patients to discontinue bupropion and contact their clinician if symptoms of a possible hypersensitivity reaction occur.

General 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 in patients receiving bupropion or varenicline for smoking cessation; has occurred in patients with or without psychiatric history.

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. 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.

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.

Monitor patients for neuropsychiatric symptoms or for worsening of preexisting psychiatric conditions. 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. Provide ongoing monitoring and supportive care until symptoms resolve.

Seizures

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

Drug is contraindicated in patients with a seizure disorder, anorexia nervosa or bulimia, or undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Risk factors 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).

If patients experience a seizure during therapy, discontinue drug and do not restart.

Hypertension

Hypertension (sometimes severe) has occurred with bupropion therapy either alone or in combination with transdermal nicotine in patients with and without preexisting hypertension. Risk of hypertension is increased with concomitant use of MAO inhibitors (contraindicated) or other dopaminergic or noradrenergic drugs; also increased with concomitant transdermal nicotine therapy.

Safety in patients with recent history of MI or unstable heart disease not established.

Assess BP before initiating bupropion and monitor periodically during therapy, especially in patients receiving concomitant nicotine replacement therapy.

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.

Bupropion is not FDA-labeled for use in treating bipolar depression. 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.

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. Some of these patients had a diagnosis of bipolar disorder. In some cases, symptoms diminished with dosage reduction or withdrawal of therapy. Similar types of neuropsychiatric manifestations reported during postmarketing experience in patients receiving the drug for smoking cessation.

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

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.

Laboratory Test Interferences

False-positive results for urine immunoassay screening tests for amphetamines reported in patients receiving bupropion and following discontinuance of drug. Confirmatory tests (e.g., gas chromatography/mass spectrometry) can distinguish bupropion from amphetamines.

Specific Populations

Pregnancy

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

National Pregnancy Registry for Antidepressants at 844-405-6185 or [Web].

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.

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

Lactation

Distributed into milk. Effects of bupropion or its metabolites on milk production not known.

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. Postmarketing reports of seizures in breast-fed infants; however, causal relationship not established.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

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). 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. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of bupropion in a child or adolescent for any clinical use.

Has been used in a limited number of children 7–16 years of age for attention deficit disorder^† without unusual adverse effect.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults; however, possibility of increased sensitivity to drug in some older patients cannot be ruled out.

Consider increased possibility of impaired renal function, which may increase risk of adverse effects, when selecting dosage; may be useful to monitor renal function.

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.

Hepatic Impairment

Reduced dosage required in patients with severe hepatic impairment (Child-Pugh score: 7–15). In patients with mild hepatic impairment (Child-Pugh score: 5–6), consider reduced frequency and/or dosage.

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

Renal Impairment

Use with caution; parent drug and active metabolites may accumulate. Monitor closely for adverse effects that could indicate high bupropion or metabolite exposures; reduction in dosage and/or frequency may be necessary.

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

Common Adverse Effects

Common 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.

Common adverse effects (≥5%) in patients receiving bupropion hydrochloride extended-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.

Common 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.

Common 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.

Common adverse effects (≥5%) in 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, rash.

Drug Interactions

Metabolized to hydroxybupropion, principally by CYP2B6; CYP isoenzymes not involved in the formation of other bupropion metabolites.

Bupropion and its metabolites inhibit CYP2D6.

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered serum concentrations of bupropion) with drugs that induce or inhibit CYP2B6.

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations). Dosage reduction of the CYP2D6 substrate may be necessary, particularly for drugs with a narrow therapeutic index.

Prodrugs dependent on CYP2D6 for activation: Possible reduced clinical efficacy of the prodrug. An increase in dosage of the prodrug may be necessary.

Smoking Cessation

Smoking may induce enzymes and increase metabolism of some drugs. 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.

Specific Drugs

buPROPion Pharmacokinetics

Absorption

Bioavailability

Well-absorbed from the GI tract following oral administration. Peak plasma 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. 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). Peak plasma concentrations occur within approximately 5 hours after oral administration of extended-release bupropion hydrobromide tablets (Aplenzin).

Steady-state plasma concentrations of bupropion achieved within 8 days.

At steady state, conventional and extended-release tablets (Wellbutrin SR, Wellbutrin XL) are essentially bioequivalent.

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

Food

Food does not appear to substantially affect the peak plasma concentration or extent of absorption achieved with extended-release tablets.

Distribution

Extent

Bupropion and its metabolites are distributed into milk.

Plasma Protein Binding

84% bound to human albumin.

Elimination

Metabolism

Extensively metabolized in the liver to 3 active metabolites: hydroxybupropion (principally by CYP2B6), threohydrobupropion, and erythrohydrobupropion. CYP isoenzymes not involved in the formation of threohydrobupropion and erythrohydrobupropion metabolites.

Elimination Route

Excreted in urine (87%) and feces (10%), principally as metabolites.

Half-life

The half-life in the terminal phase (t_½β) averages about 14 hours following single doses; with multiple dosing, t_½β reportedly averages 21 hours.

Special Populations

Hepatic impairment can decrease elimination of bupropion.

Renal impairment may decrease elimination of major metabolites.

Stability

Storage

Oral

Conventional Bupropion Hydrochloride Tablets

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

Extended-release Bupropion Hydrochloride Tablets

Extended-release (e.g., Wellbutrin SR): 20–25°C (excursions permitted to 15–30°C); protect from light and moisture.

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

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

Extended-release Bupropion Hydrobromide Tablets

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

Actions

• Chemically unrelated to tricyclic, tetracyclic, or other currently available antidepressants (e.g., SSRIs); also chemically unrelated to nicotine or other agents currently used in treatment of nicotine dependence.

• Mechanism of antidepressant action is unclear; noradrenergic and/or dopaminergic pathways appear to be principally involved. Relatively weak inhibitor of the neuronal reuptake of norepinephrine and dopamine; does not inhibit monoamine oxidase or reuptake of serotonin.

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

• Produces less frequent anticholinergic effects, cardiovascular effects, antihistaminic effects, and weight gain compared with tricyclic antidepressants at usual dosages.

Advice to Patients

• Advise patients to swallow tablets whole and not to crush, chew, or divide the tablets.

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

• Instruct patients to take bupropion hydrochloride extended-release tablets in 2 divided doses, preferably with ≥8 hours between successive doses, when doses are >150 mg daily to minimize the risk of seizures.

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

• 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.

• Risk of suicidality with antidepressants; instruct patients, families, and caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, suicidality, or worsening depression, especially during the first few months of therapy or during periods of dosage adjustment. 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. Such symptoms may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in medication.

• 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. Instruct patients to discontinue bupropion and contact a clinician if they experience such symptoms.

• Risk of hyperensitivity reactions. Advise patients to stop taking bupropion and notify their clinician if they develop signs of a severe allergic reaction.

• Risk of seizures. Advise patients to permanently stop taking the drug and immediately notify their clinician if they have a seizure. Advise patients that excessive use or abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedative hypnotic drugs can increase the risk of seizure. Advise patients to minimize or avoid use of alcohol.

• Risk of angle-closure glaucoma in susceptible individuals secondary to mild pupillary dilation associated with bupropion. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy) if they are susceptible.

• Importance of avoiding concomitant therapy with preparations containing bupropion for use as an adjunct in smoking cessation and preparations used for treatment of major depressive disorder or seasonal affective disorder.

• May impair patient's ability to perform tasks requiring judgment or motor and cognitive skills. Advise patients to avoid operating machinery or driving a motor vehicle until the effects on the individual are known. May decrease alcohol tolerance.

• Importance of minimizing or avoiding consumption of alcohol; excessive use of alcohol or abrupt cessation of use may alter the seizure threshold.

• Importance of informing patients that the shell of certain extended-release tablets (e.g., Aplenzin, Wellbutrin XL) does not dissolve and may be passed in the stool.

• Advise patients that bupropion hydrochloride extended-release tablets (e.g., Wellbutrin SR) may have an odor.

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.

• Importance of women notifying clinicians if they are or plan to become pregnant or plan to breast-feed. Advise patients of any pregnancy exposure registry that monitors pregnancy outcomes in women exposed to bupropion during pregnancy. Advise patients that bupropion in distributed into milk in small amounts.

• Importance of informing patients of other important precautionary information.

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

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Frequently asked questions

• How long does it take Wellbutrin XL/SR (bupropion) to work?
• Does Auvelity work better than Wellbutrin?
• Auvelity vs. Wellbutrin: Effectiveness for Depression?

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