Bupropion: Drug information
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(For additional information see "Bupropion: Patient drug information" and see "Bupropion: Pediatric drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidality and antidepressant drugs:

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects aged 65 and older.

In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Bupropion is not approved for use in pediatric patients.

Brand Names: US
  • Aplenzin;
  • Buproban [DSC];
  • Forfivo XL;
  • Wellbutrin SR;
  • Wellbutrin XL;
  • Wellbutrin [DSC];
  • Zyban
Brand Names: Canada
  • Bupropion SR;
  • Mylan-Bupropion XL;
  • Novo-Bupropion SR;
  • PMS-Bupropion SR;
  • ratio-Bupropion SR;
  • Sandoz-Bupropion SR;
  • Wellbutrin SR;
  • Wellbutrin XL;
  • Zyban
Pharmacologic Category
  • Antidepressant, Dopamine/Norepinephrine-Reuptake Inhibitor;
  • Smoking Cessation Aid
Dosing: Adult

Depression: Oral: Note: Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used.

Immediate release hydrochloride salt: Initial: 100 mg twice daily; after 3 days may increase to the usual dose of 100 mg 3 times a day; if no clinical improvement after several weeks, may increase to a maximum dose of 450 mg/day in 3 or 4 divided doses; do not exceed 150 mg in a single dose

Sustained release hydrochloride salt: Initial: 150 mg daily in the morning; if tolerated, after 3 days, may increase to a target dose of 150 mg twice daily; if no clinical improvement after several weeks, may increase to a maximum dose of 200 mg twice daily; do not exceed 200 mg in a single dose

Extended release:

Hydrochloride salt (Wellbutrin XL): Initial: 150 mg once daily in the morning; if tolerated, as early as day 4, may increase to 300 mg once daily (maximum dose: 300 mg/day; however, guidelines suggest up to 450 mg/day may be used [APA 2010]).

Hydrochloride salt (Forfivo XL): Switching from Wellbutrin immediate release, SR, or XL to Forfivo XL: Patients receiving 300 mg daily of bupropion hydrochloride for at least 2 weeks and requiring a dose increase or patients already taking 450 mg daily of bupropion hydrochloride may switch to Forfivo XL 450 mg once daily.

Hydrobromide salt (Aplenzin): Initial: 174 mg once daily in the morning; may increase as early as day 4 of dosing to 348 mg once daily (target dose)

Switching from hydrochloride salt formulation (eg, Bupropion immediate release, SR, XL, or Forfivo XL) to hydrobromide salt formulation (Aplenzin):

Bupropion hydrochloride 150 mg daily is equivalent to bupropion hydrobromide 174 mg once daily

Bupropion hydrochloride 300 mg daily is equivalent to bupropion hydrobromide 348 mg once daily

Bupropion hydrochloride 450 mg daily is equivalent to bupropion hydrobromide 522 mg once daily

Seasonal affective disorder (SAD): Initial: 150 mg once daily (Wellbutrin XL) or 174 mg once daily (Aplenzin) in the morning; if tolerated, may increase after 7 days to 300 mg once daily (Wellbutrin XL) or 348 mg once daily (Aplenzin) in the morning.

Note: Prophylactic treatment should be reserved for those patients with frequent depressive episodes and/or significant impairment. Initiate treatment in the Autumn prior to symptom onset, and discontinue in early Spring with dose tapering. Doses >300 mg daily (Wellbutrin XL) or >348 mg daily (Aplenzin) have not been studied in SAD

Smoking cessation (Zyban): Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily (maximum dose: 300 mg/day).

Note: Therapy should begin at least 1 week before target quit date. Target quit dates are generally in the second week of treatment. If patient successfully quits smoking after 7 to 12 weeks, may consider ongoing maintenance therapy based on individual patient risk:benefit. Efficacy of maintenance therapy (300 mg daily) has been demonstrated for up to 6 months. Conversely, if significant progress has not been made by the seventh week of therapy, success is unlikely and treatment discontinuation should be considered.

Dosing conversion between hydrochloride salt immediate, sustained, and extended release products: Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for sustained (twice daily) or extended (once daily) release products.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to allow for the detection of re-emerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (APA 2010).

Manufacturer’s labeling:

Aplenzin: In patients receiving 348 mg once daily, taper dose down to 174 mg once daily prior to discontinuing.

Forfivo XL: Because the 450 mg tablet is the only available dose formulation, use another bupropion formulation for tapering the dose prior to discontinuation.

Wellbutrin XL: In patients receiving 300 mg once daily, taper dose down to 150 mg once daily prior to discontinuing.

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor antidepressant:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat depression and initiation of bupropion.

Allow 14 days to elapse between discontinuing bupropion and initiation of an MAO inhibitor intended to treat depression.

Antidepressant-induced sexual dysfunction (off-label use): Oral: Sustained release: Initial: 150 mg once daily for the first 3 days; increase to 150 mg twice daily, based on response and tolerability (Clayton 2004; Safarinejad 2011).

Attention-deficit/hyperactivity disorder (off-label use): Oral:

Sustained release: Initial: 100 mg once daily in the morning; increase weekly in 100 mg/day increments based on response and tolerability up to 200 mg twice daily (Reimherr 2005; Wilens 2001)

Extended release: Initial: 150 mg once daily in the morning for 1 week; increase to 300 mg once daily for 3 weeks; may further increase dose based on response and tolerability up to 450 mg once daily (Wilens 2005).

Depression associated with bipolar disorder (off-label use): Oral: Initial: 100 mg/day; increase based on response and tolerability at 2-week intervals up to 450 mg/day (average dose in clinical trials was 250 mg/day) (Grossman 1999; McIntyre 2002).

Obesity (off-label use): Oral: Sustained release: Initial: 150 mg once daily in the morning; increase to 150 mg twice daily after 3 days; may further increase dose after 2 weeks based on response and tolerability to 200 mg twice daily (dose-dependent responses were identified in one clinical trial) (Anderson 2002; Gadde 2001; Jain 2002).

Dosing: Pediatric

(For additional information see "Bupropion: Pediatric drug information")

ADHD (off-label use): Children and Adolescents: Oral:

Immediate release: Initial: 3 mg/kg/day in 2 to 3 divided doses; maximum initial dose 150 mg/day; increase dose as needed to a maximum daily dose of 6 mg/kg/day or 300 mg/day with no single dose > 150 mg. (AACAP [Pliszka 2007])

Sustained release and extended release: May use in place of immediate-release tablets, once the daily dose is increased using the immediate release product and the 12-hour dosage corresponds to a sustained-release tablet size or the 24-hour dosage corresponds to an extended release tablet size.

MAO inhibitor recommendations: Refer to adult dosing.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Dosing: Renal Impairment

Use with caution; manufacturer’s labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations. Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Zyban product labeling defines renal impairment as GFR <90 mL/minute.

Forfivo XL: Use is not recommended.

Dosing: Hepatic Impairment

Mild impairment (Child-Pugh score 5 to 6): Use with caution; manufacturer’s labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations.

Forfivo XL: Use is not recommended.

Moderate to severe impairment, including severe hepatic cirrhosis (Child-Pugh score 7 to 15): Use with extreme caution; maximum dose:

Aplenzin: 174 mg every other day

Bupropion immediate release: 75 mg once daily

Forfivo XL: Use is not recommended.

Wellbutrin SR: 100 mg once daily or 150 mg every other day

Wellbutrin XL, Zyban: 150 mg every other day

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as hydrochloride:

Wellbutrin: 75 mg [DSC], 100 mg [DSC]

Generic: 75 mg, 100 mg

Tablet Extended Release 12 Hour, Oral, as hydrochloride:

Buproban: 150 mg [DSC]

Wellbutrin SR: 100 mg, 150 mg, 200 mg

Zyban: 150 mg

Generic: 100 mg, 150 mg, 200 mg

Tablet Extended Release 24 Hour, Oral, as hydrobromide:

Aplenzin: 174 mg, 348 mg, 522 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Forfivo XL: 450 mg

Wellbutrin XL: 150 mg, 300 mg

Generic: 150 mg, 300 mg

Generic Equivalent Available (US)

Yes

Dosage Forms: Canada

Information with regard to form, strength, and availability of products uniquely available in Canada but currently not available in the US. Refer also to Dosage forms.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Administration

May be taken without regard to meals. The manufacturer states that tablets should be swallowed whole; do not crush, chew, or divide.

Extended release: Administer once daily with at least 24 hours between successive doses.

Immediate release: Administer 3 to 4 times daily with at least 6 hours between successive doses; do not exceed 150 mg in a single dose.

Sustained release: Administer 2 times daily with at least 8 hours between successive doses; do not exceed 200 mg in a single dose.

Use

Major depressive disorder (Aplenzin, Bupropion immediate release, Forfivo XL, Wellbutrin SR, Wellbutrin XL): Treatment of major depressive disorder (MDD).

Seasonal affective disorder (Aplenzin, Wellbutrin XL): Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD).

Smoking cessation (Zyban): As an aid to smoking cessation treatment.

Use: Off-Label

Antidepressant-induced sexual dysfunction; Attention deficit hyperactivity disorder (adults); Attention deficit hyperactivity disorder (children/adolescents); Depression associated with bipolar disorder; Obesity

Medication Safety Issues
Sound-alike/look-alike issues:

Aplenzin may be confused with Albenza, Relenza

BuPROPion may be confused with busPIRone

Forfivo XL may be confused with Forteo

Wellbutrin XL may be confused with Wellbutrin SR

Zyban may be confused with Diovan

Adverse Reactions

>10%:

Cardiovascular: Tachycardia (≤11%)

Central nervous system: Insomnia (11% to 40%), headache (25% to 34%), agitation (2% to 32%), dizziness (6% to 22%)

Dermatologic: Diaphoresis (5% to 22%)

Endocrine & metabolic: Weight loss (14% to 23%)

Gastrointestinal: Xerostomia (10% to 28%), constipation (8% to 26%), nausea and vomiting (23%), nausea (1% to 18%)

Neuromuscular & skeletal: Tremor (1% to 21%)

Ophthalmic: Blurred vision (3% to 15%)

Respiratory: Nasopharyngitis (13%), pharyngitis (3% to 13%), rhinitis (12%)

1% to 10%:

Cardiovascular: Palpitations (2% to 6%), cardiac arrhythmia (5%), chest pain (≤4%), flushing (≤4%), hypertension (1% to 4%; may be severe), hypotension (3%)

Central nervous system: Lack of concentration (9%), confusion (≤8%), anxiety (3% to 8%), hostility (≤6%), nervousness (4% to 5%), abnormal dreams (3% to 5%), sensory disturbance (4%), sleep disorder (4%), migraine (≤4%), irritability (3%), memory impairment (≤3%), drowsiness (2% to 3%), pain (3%), akathisia (≤2%), central nervous system stimulation (≤2%), paresthesia (≤2%), twitching (≤2%), dystonia (≥1%), abnormality in thinking (1%), depression

Dermatologic: Skin rash (1% to 8%), pruritus (2% to 4%), xeroderma (2%), urticaria (1% to 2%)

Endocrine & metabolic: Weight gain (9%), menstrual disease (2% to 5%), decreased libido (≤3%), hot flash (1% to 3%)

Gastrointestinal: Abdominal pain (2% to 9%), diarrhea (4% to 7%), flatulence (6%), anorexia (1% to 5%), dysgeusia (2% to 4%), increased appetite (2% to 4%), vomiting (≥1% to 4%), dyspepsia (3%), oral mucosa ulcer (2%), dysphagia (≤2%)

Genitourinary: Urinary frequency (≥1% to 5%), urinary urgency (≤2%), vaginal hemorrhage (≤2%), urinary tract infection (≤1%)

Hypersensitivity: Hypersensitivity reaction (1%)

Infection: Infection (8% to 9%)

Neuromuscular & skeletal: Myalgia (2% to 6%), arthralgia (4% to 5%), weakness (4%), neck pain (2%), arthritis (≤2%), dyskinesia (≥1%)

Otic: Tinnitus (1% to 6%), auditory disturbance (5%)

Renal: Polyuria (≤1%)

Respiratory: Upper respiratory infection (9%), sinusitis (2% to 5%), cough (2% to 4%), increased cough (2% to 3%), epistaxis (2%), bronchitis (≤2%)

Miscellaneous: Accidental injury (2%), fever (1% to 2%)

Frequency not defined: Ophthalmic: Diplopia (≤3%)

<1%, postmarketing, and/or case reports: Abnormal accommodation, abnormal stools, aggressive behavior, akinesia, alopecia, amnesia, anaphylactic shock, anaphylactoid reaction, anaphylaxis, anemia, angioedema, angle-closure glaucoma, aphasia, ataxia, atrioventricular block, bronchospasm, bruxism, cerebrovascular accident, change in prothrombin time, chills, colitis, coma, complete atrioventricular block, cystitis, deafness, delayed hypersensitivity, delirium, delusions, depersonalization, derealization, drug-induced Parkinson disease, dry eye syndrome, dysarthria, dyspareunia, dysphoria, dysuria, ecchymoses, edema, EEG pattern changes, ejaculatory disorder, emotional lability, erythema multiforme, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal reaction, extrasystoles, facial edema, gastric ulcer, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, gingivitis, glossitis, glycosuria, gynecomastia, hallucination, hepatic injury, hepatic insufficiency, hepatitis, hirsutism, homicidal ideation, hyperglycemia, hyperkinesia, hypertonia, hypoesthesia, hypoglycemia, hypokinesia, hypomania, hyponatremia, impotence, increased intraocular pressure, increased libido, increased thirst, inguinal hernia, intestinal perforation, jaundice, leg cramps, leukocytosis, leukopenia, lymphadenopathy, maculopapular rash, malaise, manic behavior, menopause, muscle rigidity, musculoskeletal chest pain, myasthenia, mydriasis, myocardial infarction, myoclonus, neuralgia, neuropathy, orthostatic hypotension, painful erection, pancreatitis, pancytopenia, panic, paranoia, peripheral edema, phlebitis, pneumonia, prostatic disease, psychiatric signs and symptoms, psychosis, pulmonary embolism, restlessness, rhabdomyolysis, salpingitis, sciatica, seizure (dose-related), serum sickness-like reaction, SIADH, sialorrhea, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, suicidal ideation, syncope, tardive dyskinesia, thrombocytopenia, tongue edema, urinary incontinence, urinary retention, vaginitis, vasodilatation, vertigo

Contraindications

Hypersensitivity to bupropion or any component of the formulation; seizure disorder; history of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives, including benzodiazepines, barbiturates, or antiepileptic drugs; use of MAO inhibitors (concurrently or within 14 days of discontinuing either bupropion or the MAO inhibitor); initiation of bupropion in a patient receiving linezolid or intravenous methylene blue

Aplenzin, Forfivo XL, Wellbutrin XL: Additional contraindications: Other conditions that increase seizure risk, including arteriovenous malformation, severe head injury, severe stroke, CNS tumor, CNS infection

Forfivo XL: Additional contraindications: Patients receiving other dosage forms of bupropion

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use or use within 14 days of thioridazine; concurrent use with other dosage forms of bupropion

Warnings/Precautions

Major psychiatric warnings (use in treating psychiatric disorders):

• Suicidal thinking/behavior (use in treating psychiatric disorders): [US Boxed Warning]: Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); advise families and caregivers of the need for close observation and communication with the prescriber. A medication guide concerning the use of antidepressants should be dispensed with each prescription.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• CNS stimulation: May cause CNS stimulation (restlessness, anxiety, insomnia) or anorexia.

• Cognitive impairment: May cause motor or cognitive impairment in some patients, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hypersensitivity reactions: Anaphylactoid/anaphylactic reactions have occurred, with symptoms of pruritus, urticaria, angioedema, and dyspnea. Serious reactions have been (rarely) reported, including erythema multiforme, Stevens-Johnson syndrome and anaphylactic shock. Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity resembling serum sickness have been reported.

• Hypertension: May elevate blood pressure and cause hypertension. Events have been observed in patients with or without evidence of preexisting hypertension. The risk is increased when used concomitantly with monoamine oxidase inhibitors, nicotine replacement, or other drugs that increase dopaminergic or noradrenergic activity. Assess blood pressure before treatment and monitor periodically.

• Mania/hypomania: May precipitate a manic, mixed, or hypomanic episode; risk is increased in patients with bipolar disorder or who have risk factors for bipolar disorder. Screen patients for a history of bipolar disorder and the presence of risk factors including a family history of bipolar disorder, suicide, or depression. Bupropion is not FDA approved for bipolar depression.

• Neuropsychiatric effect (use in smoking cessation): Serious neuropsychiatric events have occurred in patients taking bupropion for smoking cessation, including changes in mood (eg, depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide. The majority occurred during bupropion treatment; some occurred during treatment discontinuation. A causal relationship is uncertain as depressed mood may be a symptom of nicotine withdrawal. Some cases also occurred in patients taking bupropion who continued to smoke. Neuropsychiatric effects occurred in patients with and without preexisting psychiatric disease; some patients experienced a worsening of their psychiatric illnesses. However, subsequent controlled trials in patients with or without psychiatric disorders have not identified significant differences in neuropsychiatric effects for patients taking bupropion, varenicline, nicotine patches, or placebo (Anthenelli 2016; Cinciripini 2013). Observe all patients taking bupropion for neuropsychiatric reactions. Instruct patients to stop taking bupropion and contact a health care provider if neuropsychiatric reactions occur.

• Ocular effects: May cause mild pupillary dilation, which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Psychosis: May cause delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion; most common in depressed patients and patients with a diagnosis of bipolar disorder. Symptoms may abate with dose reduction and/or withdrawal of treatment.

• Seizures: May cause a dose-related risk of seizures. Use is contraindicated in patients with a history of seizures or certain conditions with high seizure risk (eg, history of anorexia/bulimia or patients undergoing abrupt discontinuation of ethanol, benzodiazepines, barbiturates, or antiepileptic drugs). Aplenzin, Forfivo XL, and Wellbutrin XL are also contraindicated in patients with certain conditions with high seizure risk (eg, arteriovenous malformation, severe head injury, severe stroke, CNS tumor, and CNS infection). Use caution with concurrent use of antipsychotics, antidepressants, theophylline, systemic corticosteroids, stimulants (including cocaine), anorexiants, or hypoglycemic agents, or with excessive use of ethanol, benzodiazepines, sedative/hypnotics, or opioids. Use with caution in seizure-potentiating metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia). The dose-dependent risk of seizures may be reduced by gradual dose increases and by not exceeding the maximum daily dose. Do not coadminister with other bupropion-containing formulations; Forfivo XL is contraindicated in patients receiving other dosage forms of bupropion. Permanently discontinue if seizure occurs during therapy. Chewing, crushing, injecting, or dividing long-acting products may increase seizure risk.

• Sexual dysfunction: The incidence of sexual dysfunction with bupropion is generally lower than with SSRIs (Clayton 2004).

• Weight loss: May cause weight loss; use caution in patients where weight loss is not desirable.

Disease-related concerns:

• ADHD (off-label use): All children diagnosed with ADHD who may be candidates for stimulant medications should have a thorough cardiovascular assessment to identify risk factors for sudden cardiac death prior to initiation of drug therapy.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease, history of hypertension, or coronary artery disease; treatment-emergent hypertension (including some severe cases) has been reported, both with bupropion alone and in combination with nicotine transdermal systems.

• Hepatic impairment: Use with caution in patients with hepatic impairment; consider a reduction in dose and/or frequency; Forfivo XL is not recommended in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; consider a reduction in dose and/or frequency; Forfivo XL is not recommended in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; may be at greater risk of drug accumulation during chronic dosing. Consider a reduction in dose.

Dosage form specific issues:

• Extended release tablet: Insoluble tablet shell may remain intact and be visible in the stool.

Other warnings/precautions:

• Abuse/misuse: Using doses higher than prescribed may result in increased motor activity, agitation/excitement and euphoria. Inhalation of crushed tablets or injection of dissolved bupropion has been reported, some resulting in seizures and death.

• Electroconvulsive therapy (ECT): May increase the risks associated with ECT; consider discontinuing, when possible, prior to ECT treatment (APA 2010).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2A6 (minor), CYP2B6 (major), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate), OCT2

Drug Interactions

(For additional information: Launch drug interactions program)

Agents With Seizure Threshold Lowering Potential: BuPROPion may enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of BuPROPion. Specifically, seizure threshold may be lowered. BuPROPion may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may decrease during treatment. Management: Patients receiving bupropion should be advised to minimize or avoid alcohol consumption due to possible lower alcohol tolerance, and lower seizure threshold associated with heavy alcohol consumption/abrupt discontinuation of heavy consumption. Risk D: Consider therapy modification

Amifampridine: May enhance the adverse/toxic effect of BuPROPion. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Risk C: Monitor therapy

Antihepaciviral Combination Products: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): May enhance the adverse/toxic effect of BuPROPion. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Risk C: Monitor therapy

Citalopram: BuPROPion may enhance the adverse/toxic effect of Citalopram. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion, and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Risk D: Consider therapy modification

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

CYP2B6 Inducers (Moderate): May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2B6 Inhibitors (Weak): May increase the serum concentration of BuPROPion. Exceptions: Prasugrel. Risk C: Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

Digoxin: BuPROPion may decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Dipyrone: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification

Efavirenz: May decrease the serum concentration of BuPROPion. Management: Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Risk C: Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

FLUoxetine: BuPROPion may enhance the adverse/toxic effect of FLUoxetine. BuPROPion may increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

FluvoxaMINE: BuPROPion may enhance the adverse/toxic effect of FluvoxaMINE. BuPROPion may increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

Ioflupane I 123: BuPROPion may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Isavuconazonium Sulfate: May decrease the serum concentration of BuPROPion. Risk C: Monitor therapy

Lopinavir: May decrease the serum concentration of BuPROPion. Concentrations of the active metabolite, hydroxybupropion, may also be decreased. Management: Monitor bupropion response closely. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving lopinavir. Risk C: Monitor therapy

Lorcaserin: BuPROPion may enhance the serotonergic effect of Lorcaserin. This could result in serotonin syndrome. Management: Seek alternatives to this combination when possible. Risk D: Consider therapy modification

Lumacaftor: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Risk D: Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of BuPROPion. Risk X: Avoid combination

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nilotinib: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor therapy

OCT2 Substrates: BuPROPion may increase the serum concentration of OCT2 Substrates. Risk C: Monitor therapy

PARoxetine: BuPROPion may enhance the adverse/toxic effect of PARoxetine. BuPROPion may increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Risk D: Consider therapy modification

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Ritonavir: May decrease the serum concentration of BuPROPion. Mixed effects on concentrations of the active hydroxybupropion metabolite have been reported. Management: Monitor for decreased bupropion effects. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving ritonavir. Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy

Tricyclic Antidepressants: BuPROPion may decrease the metabolism of Tricyclic Antidepressants. Management: Seek alternatives when possible. Monitor patients receiving these combinations closely for increased serum concentrations (when testing is available) and toxic effects of the tricyclic antidepressant. Exceptions: Amoxapine; Protriptyline. Risk D: Consider therapy modification

Vortioxetine: BuPROPion may enhance the adverse/toxic effect of Vortioxetine. BuPROPion may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with bupropion. Following cessation of bupropion, the vortioxetine dose should be returned to the normal level. Risk D: Consider therapy modification

Pregnancy Risk Factor

C (show table)

Pregnancy Implications

Adverse events have been observed in some animal reproduction studies. Bupropion and its metabolites were found to cross the placenta in in vitro studies (Earhart 2012). An increased risk of congenital malformations has not been observed following maternal use of bupropion during pregnancy; however, data specific to cardiovascular malformations is inconsistent. The long-term effects on development and behavior have not been studied.

The ACOG recommends that antidepressant therapy during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009). There is insufficient information related to the use of bupropion to recommend use in pregnancy (ACOG 2010).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breast-Feeding Considerations

Bupropion and its active metabolites are present in breast milk.

The manufacturer reports the relative infant dose (RID) of bupropion and its active metabolites to be ~2% of a weight-adjusted maternal dose. In one report, the RID of bupropion ranged from 1.4% to 10.6% of the maternal dose when calculated using actual infant weights and maternal doses ranging from 150 to 300 mg/day (Davis 2009). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015). When an RID is >25%, breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Bupropion and its active metabolites can also be detected in the serum and urine of breastfeeding infants (Davis 2009; Neuman 2014).

Seizures and sleep disturbances have been reported in breastfeeding infants following bupropion exposure via breast milk (Chaudron 2004; Hale 2010; Neuman 2014). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015).

When first initiating an antidepressant in a breastfeeding woman, agents other than bupropion are preferred (Berle 2011); however, maternal use of bupropion is not considered a reason to discontinue breastfeeding (Sriraman 2015). The manufacturer recommends that caution be exercised when administering bupropion to breastfeeding women.

Monitoring Parameters

Body weight; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; blood pressure (baseline and periodically especially when used in conjunction with nicotine transdermal replacement); renal and hepatic function

When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter 2008).

Reference Range

Therapeutic levels have not been well established and are not routinely recommended. Studies have suggested optimal antidepressant response may occur at trough bupropion plasma concentrations <100 µg/L (ng/mL) with some patients having a better response at lower levels of 10 to 50 µg/L (ng/mL; Burke 1999; Goodnick 1992; Preskorn 1983). For bupropion plus hydroxybupropion (active metabolite) AGNP Consensus Guidelines for therapeutic drug monitoring recommend trough levels with reference range of 225 to 1,500 ng/mL with an alert for levels ≥2,000 ng/mL (Hiemke 2011).

Mechanism of Action

Aminoketone antidepressant structurally different from all other marketed antidepressants; like other antidepressants the mechanism of bupropion's activity is not fully understood. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Metabolite inhibits the reuptake of norepinephrine. The primary mechanism of action is thought to be dopaminergic and/or noradrenergic.

Pharmacodynamics/Kinetics

Onset of action: 1 to 2 weeks

Duration of action: 1 to 2 days

Absorption: Rapid

Distribution: Vd: ~20 to 47 L/kg (Laizure 1985)

Protein binding: 84%

Metabolism: Extensively hepatic via CYP2B6 to hydroxybupropion; non-CYP-mediated metabolism to erythrohydrobupropion and threohydrobupropion. Metabolite activity ranges from 20% to 50% potency of bupropion. Bupropion also undergoes oxidation to form the glycine conjugate of meta-chlorobenzoic acid, the major urinary metabolite.

Half-life:

Distribution: 3 to 4 hours

Elimination: ~21 hours after chronic dosing (range: 12 to 30 hours); Metabolites (after a single dose): Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours

Extended release (Aplenzin): 21 ± 7 hours; Metabolites: Hydroxybupropion: 24 ± 5 hours; Erythrohydrobupropion: 31 ± 8 hours; Threohydrobupropion: 51 ± 9 hours

Time to peak, serum:

Bupropion: Immediate release: Within 2 hours; Sustained release: Within 3 hours; Extended release: ~5 hours (Forfivo XL: 5 hours [fasting]; 12 hours [fed])

Metabolite: Hydroxybupropion: Immediate release: ~3 hours; Extended release, sustained release: ~6 to 7 hours

Excretion: Urine (87%, primarily as metabolites); feces (10%, primarily as metabolites)

Pricing: US

Tablet, 12-hour (BuPROPion HCl ER (Smoking Det) Oral)

150 mg (60): $116.10

Tablet, 12-hour (BuPROPion HCl ER (SR) Oral)

100 mg (100): $168.90

150 mg (100): $193.30

200 mg (60): $215.59

Tablet, 12-hour (Wellbutrin SR Oral)

100 mg (60): $484.03

150 mg (60): $518.76

200 mg (60): $963.32

Tablet, 12-hour (Zyban Oral)

150 mg (60): $297.32

Tablet, 24-hour (Aplenzin Oral)

174 mg (30): $1,561.90

348 mg (30): $2,058.96

522 mg (30): $4,685.58

Tablet, 24-hour (BuPROPion HCl ER (XL) Oral)

150 mg (30): $143.20

300 mg (30): $172.71

Tablet, 24-hour (Forfivo XL Oral)

450 mg (30): $513.22

Tablet, 24-hour (Wellbutrin XL Oral)

150 mg (30): $1,542.07

300 mg (30): $2,035.60

Tablets (BuPROPion HCl Oral)

75 mg (100): $79.43

100 mg (100): $106.01

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Betetrim (TW);
  • Bupep SR (IN);
  • Buprotrin (TW);
  • Buxon (CL);
  • Deppreo (VN);
  • Elontril (EE, ES, HU, LT, RO, SK);
  • Funnix (TW);
  • Le Fu Ting (CN);
  • Nicopion (KR);
  • Nicostop (VN);
  • Odranal (AR, CO);
  • Prewell (TW);
  • Prexaton (AU);
  • Quomen (TH);
  • Wellbutrin (MX, PE, PY, TW, UA, VE);
  • Wellbutrin Retard (IS, SK);
  • Wellbutrin SR (AR, BB, BM, BS, CL, CR, DO, EC, GT, HK, HN, HU, JM, KR, LV, NI, PA, SG, SV, UY);
  • Wellbutrin XL (BB, BH, BM, BS, CO, CR, DO, EC, GT, HK, HN, JM, KR, KW, NI, PA, PE, QA, SA, SV, TH, TW);
  • Wellbutrin XR (CY, HR, IL, LU, MT, SI, TR, UA);
  • Yue Ting (CN);
  • Zyban (AE, AT, BB, BE, BG, BM, BR, BS, BZ, CH, CY, CZ, DE, DK, FI, FR, GB, GR, GY, IE, IL, IN, IS, IT, JM, MT, NL, NO, NZ, PL, PR, PT, RO, SA, SE, SI, SR, TR, TT, UA);
  • Zyban LP (FR);
  • Zyban SR (BH, KW, QA, SG);
  • Zyban Sustained Release (AU);
  • Zylexx SR (PK);
  • Zyntabac (ES)
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