BuPROPion (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressant drugs:
Pronunciation

(byoo PROE pee on)

Brand Names: US

Aplenzin; Buproban [DSC]; Forfivo XL; Wellbutrin SR; Wellbutrin XL; Wellbutrin [DSC]; Zyban

Brand Names: Canada

ACT BuPROPion XL; MYLAN-BuPROPion XL; NOVO-BuPROPion SR [DSC]; PMS-BuPROPion SR; RATIO-BuPROPion SR [DSC]; SANDOZ BuPROPion; Wellbutrin SR; Wellbutrin XL; Zyban

Dosing: Adult

Note: Bupropion is available as hydrochloride and hydrobromide salts. Doses are expressed in this monograph as hydrochloride salt except where noted as bupropion hydrobromide salt. Bupropion hydrochloride 150 mg is equivalent to about 174 mg of bupropion hydrobromide. Bupropion is available as immediate release, 12-hour extended release (sustained release), and 24-hour extended release tablets.

Attention-deficit/hyperactivity disorder (off-label use): Note: For patients with comorbid mood disorders or as an alternative agent for patients with substance use disorders (Brent 2019; CANMAT [Bond 2012]).

12-hour extended release (sustained release): Oral: Initial: 100 mg once daily in the morning; increase in 100 mg/day increments at intervals of 3 to 4 weeks based on response and tolerability up to 200 mg twice daily (Bukstein 2019; Reimherr 2005; Wilens 2001).

24-hour extended release: Oral: 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).

Bipolar depression (off-label use): 12-hour extended release (sustained release): Oral: Initial: 100 mg once daily as an adjunct to mood stabilizer; increase based on response and tolerability at 2-week intervals up to 450 mg/day in 2 divided doses (average dose in clinical trials was 250 mg/day) (APA 2002; Grossman 1999; McIntyre 2002).

Major depressive disorder (unipolar): Note: Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used. Slower dose titrations may be indicated based on patient care setting, symptom severity, and concern for side effects. May also be used as an alternative agent for patients with SSRI-induced sexual dysfunction (APA 2010).

Immediate release: Oral: 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.

12-hour extended release (sustained release): Oral: 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.

24-hour extended release: Oral:

Hydrochloride saltInitial: 150 mg once daily in the morning; if tolerated, may increase as early as day 4 of dosing to 300 mg once daily; if no clinical improvement after 2 weeks, may increase to 450 mg once daily.

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

Seasonal affective disorder (SAD): 24-hour extended release: Oral:

Hydrochloride salt: Initial: 150 mg once daily in the morning; if tolerated, may increase after 7 days to 300 mg once daily in the morning.

Hydrobromide salt: Initial: 174 mg once daily in the morning; if tolerated, may increase after 7 days to 348 mg once daily in the morning.

Note: Prophylactic treatment should be reserved for 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 (hydrochloride salt) or >348 mg daily (hydrobromide salt) have not been studied in SAD.

Selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction, augmentation (off-label use): 12-hour extended release (sustained release): Oral: 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).

Smoking cessation: Note: May be used as monotherapy or in combination with nicotine replacement therapy (Siu 2015): 12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily (maximum dose: 300 mg/day). For patients who do not tolerate titration to the full dose, consider continuing 150 mg once daily; the lower dose has shown efficacy (Hughes 2014).

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 1 year; however, use may be extended indefinitely based on prior quit attempts and patient preference. Conversely, if significant progress has not been made by the seventh week of therapy, success is unlikely; consider combination therapy, or discontinuation and use of an alternative agent.

Dosing conversion:

Immediate-, 12-hour (sustained release), and 24-hour extended-release formulations (hydrochloride salt): Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for immediate (3 to 4 times daily), 12-hour extended (sustained release) (twice daily), or 24-hour extended (once daily) release products.

Hydrochloride salt formulation (immediate release, 12-hour (sustained release), or 24-hour extended release) to hydrobromide salt formulation (extended release):

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.

MAOI recommendations: Switching to or from an MAOI antidepressant:

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

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

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose (eg, over 2 to 4 weeks) to allow for the detection of reemerging symptoms. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (APA 2010).

Dosing: Geriatric

Refer to adult dosing; use with caution.

Discontinuation of therapy: Refer to adult dosing.

MAOI recommendations: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Use with caution; manufacturer’s labeling suggests a reduction in dose and/or frequency be considered but does not provide specific dosing recommendations. Use of the 450 mg extended-release tablet is not recommended (Forfivo XL is not available in a lower dose strength).

Dosing: Hepatic Impairment: Adult

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. Use of the 450 mg extended-release tablet is not recommended (Forfivo XL is not available in a lower dose strength).

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

Hydrobromide salt: 174 mg every other day

Hydrochloride salt:

Immediate release: 75 mg once daily

12-hour extended release (sustained release): 100 mg once daily or 150 mg every other day

24-hour extended release: 150 mg every other day

Dosing: Pediatric

Note: Bupropion is available as either hydrochloride or hydrobromide (Aplenzin; not used in pediatric patients) salt formulations which are not interchangeable on a mg per mg basis; dosage expressed in terms of the salt formulation. Bupropion is available as immediate-release, 12-hour sustained-release, and 24-hour extended-release tablets. Patients must be able to swallow sustained or extended-release products whole.

Attention-deficit/hyperactivity disorder: Limited data available: Children ≥6 years (Dopheide 2009; Pliszka 2007) and Adolescents: Oral:

Immediate release, hydrochloride salts: Initial: 3 mg/kg/day in 2 to 3 divided doses; maximum initial dose: 150 mg/day; titrate dose as needed to a maximum daily dose of 6 mg/kg/day or 300 mg/day with no single dose >150 mg (Dopheide 2009; Pliszka 2007).

12-hour sustained release (Wellbutrin SR) and 24-hour extended release (Wellbutrin XL), hydrochloride salts: May be used in place of regular tablets, once the daily dose is titrated using the immediate release product and the titrated 12-hour dosage corresponds to a sustained release tablet (Wellbutrin SR) or the 24-hour dosage range corresponds to an extended release tablet size (Wellbutrin XL)

Depression, refractory to SSRIs: Limited data available; Note: May be most beneficial in patients with comorbid ADHD, conduct disorder, substance abuse problems or who want to quit smoking (Dopheide 2006). Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used.

Immediate release, hydrochloride salt: Children 8 to ≤11 years: Oral: Initial: 37.5 mg twice daily; titrate to response; usual dosage range: 100 to 400 mg/day (Dopheide 2006)

12-hour sustained release, hydrochloride salt (Wellbutrin SR): Children ≥11 years and Adolescents: Oral: Initial: 2 mg/kg up to 100 mg administered as a morning dose; may titrate as needed every 2 to 3 weeks using the following titration schedule: Step 2: Increase up to 3 mg/kg every morning; Step 3: Increase up to 3 mg/kg every morning and 2 mg/kg at 5 pm (17:00); Step 4: Increase up to 3 mg/kg/dose twice daily; maximum dose: 150 mg; reported mean effective dose: Morning: 2.2 mg/kg and afternoon: 1.7 mg/kg (Daviss 2001)

24-hour extended release, hydrochloride salt (Wellbutrin XL): Children ≥12 years and Adolescents: Oral: Initial: 150 mg once daily; may titrate after 2 weeks to 300 mg once daily if adequate response not achieved; dosing based on a pharmacokinetic study in eight patients with depression (Daviss 2006); doses as high as 400 mg/day have been reported (Dopheide 2006); may also be used once the daily dose is titrated using the immediate release product and the 24-hour dosage range corresponds to an extended release tablet size (Wellbutrin XL).

Smoking cessation: Limited data available: Adolescents ≥14 years and ≥40.5 kg: 12-hour sustained release, hydrochloride salt (Buproban, Zyban): Oral: Initial: 150 mg once daily for 3 days; increase to 150 mg twice daily; treatment should start while the patient is still smoking in order to allow drug to reach steady-state levels prior to smoking cessation; generally, patients should stop smoking during the second week of treatment; maximum daily dose: 300 mg/day; short-term efficacy was demonstrated in 104 adolescents who received therapy for 7 weeks with cessation counseling (Muramoto 2007).

Dosing conversion between hydrochloride salt immediate (Wellbutrin), 12-hour sustained (Wellbutrin SR), and 24-hour extended-release (Wellbutrin XL) products: Convert using same total daily dose (up to the maximum recommended dose for a given dosage form), but adjust frequency as indicated for 12-hour sustained (twice daily) or for 24-hour extended (once daily) release products.

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

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.

Dosing: Renal Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested; use with caution.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Use: Labeled Indications

Major depressive disorder (unipolar [excluding Zyban]): Treatment of major depressive disorder (MDD)

Seasonal affective disorder (24-hour extended release [Aplenzin, Wellbutrin XL]): Prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD)

Smoking cessation (12-hour extended release [sustained release; Zyban]): As an aid to smoking cessation treatment

Use: Off-Label: Adult

  Attention-deficit/hyperactivity disorderLevel of Evidence [B, G]

Data from a meta-analysis support the use of bupropion in the treatment of ADHD in adults Ref.

Based on the Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the management of mood disorders and comorbid ADHD, bupropion is first-line treatment in patients with ADHD and comorbid bipolar disorder when used as an adjunct to mood stabilizers. Additionally, these guidelines recommend bupropion as a first-line option in patients with ADHD and comorbid major depressive episodes, either as monotherapy or as an adjunct to long-acting stimulant medications. Access Full Off-Label Monograph

  Bipolar depressionLevel of Evidence [B, G]

Data from a meta-analysis support the use of bupropion in the treatment of bipolar depression. Despite demonstrating the efficacy of bupropion, the authors of this meta-analysis caution that there is a risk of switching from depression to mania when bupropion is used for this indication Ref.

Based on the American Psychiatric Association (APA) guidelines, augmentation with bupropion is second-line for the management of bipolar depression that does not respond to lithium or lamotrigine. Due to inconsistencies in bupropion augmentation clinical trial results, the World Federation of Societies of Biological Psychiatry (WFSBP) guidelinesrecommend bupropion augmentation of lithium or valproic acid as an option in patients who are unresponsive to treatments with greater evidence.

  Selective serotonin reuptake inhibitor-induced sexual dysfunction, augmentationLevel of Evidence [B, G]

Data from two randomized, double-blind, placebo-controlled trials support the use of bupropion as an augmentation strategy for increasing sexual desire, arousal, lubrication, orgasm, and satisfaction in patients with SSRI-induced sexual dysfunction who have achieved remission on a serotonergic antidepressant Ref.

Based on the APA practice guideline for the treatment of patients with major depressive disorder, bupropion given for SSRI-induced sexual dysfunction is recommended for the management of side effects of arousal, erectile dysfunction, or orgasm dysfunction.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Attention Deficit Hyperactivity Disorder (ADHD):

AHA, “Cardiovascular Monitoring of Children and Adolescents with Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder,” April 2008

American Academy of Child and Adolescent Psychiatry, “Attention-Deficit/Hyperactivity Disorder,” 2007

American Academy of Pediatrics, “ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents,” 2011

Canadian Network for Mood and Anxiety Treatments (CANMAT), “The Canadian Network for Mood and Anxiety Treatments task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder,” 2012.

National Collaborating Centre for Mental Health, “Attention Deficit Hyperactivity Disorder, NICE Guidelines,” 2009

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

COPD:

Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease, 2007 Update

GOLD 2018 Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2018

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Major Depressive Disorder in Adults,” October 2009

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Nicotine Dependence:

Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline, U.S. Department of Health and Human Services. May 2008

Administration: Oral

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

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.

12-hour extended release (sustained release): Administer 2 times daily with at least 8 hours between successive doses; do not exceed 200 mg in a single dose.

24-hour extended release: Administer once daily with at least 24 hours between successive doses.

Administration: Pediatric

Oral: May be taken without regard to meals. Do not crush, chew, or divide sustained or extended release tablets (hydrochloride and hydrobromide salt formulations); swallow whole. The insoluble shell of the extended-release tablet may remain intact during GI transit and is eliminated in the feces.

Immediate release: Administer with at least 6 hours between successive doses.

Sustained release: Typically administer 2 times daily with at least 8 hours between successive doses

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

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal pain, tremors, nightmares, nausea, vomiting, constipation, flatulence, dry mouth, insomnia, rhinitis, pharyngitis, sweating a lot, lack of appetite, or tablet shell in stool. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), confusion, seizures, thoughts of homicide, forceful actions, psychosis, behavioral changes, hallucinations, irritability, panic attacks, mood changes, agitation, severe headache, severe dizziness, passing out, excessive weight gain or loss, angina, tachycardia, abnormal heartbeat, edema, shortness of breath, hearing changes, tinnitus, polyuria, swollen glands, difficulty moving, severe joint pain, severe muscle pain, vision changes, eye pain, eye irritation, eye redness, eyelid edema, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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

24-hour extended release: Additional contraindications: Other conditions that increase seizure risk, including arteriovenous malformation, severe head injury, severe stroke, CNS tumor, CNS infection

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 health care 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 patients with an underlying psychiatric illness. 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); 24-hour extended-release formulations 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. 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.

• Renal impairment: Use with caution in patients with renal impairment; consider a reduction in dose and/or frequency.

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:

• 24-hour 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).

Geriatric Considerations

Studies have found bupropion effective as an antidepressant for older persons with major depressive disorder and as effective as paroxetine and imipramine. Its side effect profile (minimal anticholinergic and blood pressure effects) is favorable and makes it an alternative to other first-line antidepressants. A single- and multiple-dose pharmacokinetic study suggested that accumulation of bupropion and its metabolites may occur in the elderly.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011). Antidepressant trials in this patient population are small and underpowered. Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects. Treatment should be switched or augmented when response is inadequate with a therapeutic dose. Antidepressants that are not tolerated should be discontinued and an alternative agent should be started.

Warnings: Additional Pediatric Considerations

The American Heart Association recommends that all children diagnosed with ADHD who may be candidates for medication, such as bupropion, should have a thorough cardiovascular assessment prior to initiation of therapy. These recommendations are based upon reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). This assessment should include a combination of thorough medical history, family history, and physical examination. An ECG is not mandatory but should be considered.

Pregnancy Risk Factor

C

Pregnancy Considerations

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 2010). 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.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
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%), abnormal sensory symptoms (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%), asthenia (4%), neck pain (2%), arthritis (≤2%), dyskinesia (≥1%)

Ophthalmic: Diplopia (≤3%)

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%)

<1%, postmarketing, and/or case reports: Abnormal stools, accommodation disturbance, 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, delirium, delusion, 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, hyperkinetic muscle activity, hypertonia, hypoesthesia, hypoglycemia, hypokinesia, hypomania, hyponatremia, impotence, increased intraocular pressure, increased libido, increased thirst, inguinal hernia, intestinal perforation, jaundice, leukocytosis, leukopenia, lower limb cramp, 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, paranoid ideation, 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, type IV hypersensitivity reaction, urinary incontinence, urinary retention, vaginitis, vasodilatation, vertigo

Allergy and Idiosyncratic Reactions
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 (strong), OCT2

Drug Interactions 

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 (Strong) 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: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. 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 (Strong) may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph for details. Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Risk D: Consider therapy modification

AtoMOXetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses — patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Risk C: Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor; this recommendation does not apply if treating major depressive disorder. Reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor.Risk D: Consider therapy modification

Citalopram: BuPROPion may enhance the adverse/toxic effect of Citalopram. Specifically, the risk for seizures and serotonin syndrome may be increased with this combination. 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 (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification

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. Risk C: Monitor therapy

CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Tamoxifen; Timolol (Ophthalmic); Tropisetron. Risk D: Consider therapy modification

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

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

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

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 (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong 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

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

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

Escitalopram: BuPROPion may enhance the adverse/toxic effect of Escitalopram. Specifically, the risk for seizures and serotonin syndrome may be increased. Risk C: Monitor therapy

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

FLUoxetine: May enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

FluvoxaMINE: BuPROPion may enhance the adverse/toxic effect of FluvoxaMINE. Specifically, the risk for seizures and serotonin syndrome may be increased. Risk C: Monitor therapy

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

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor therapy

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

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

Iobenguane Radiopharmaceutical Products: BuPROPion may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer bupropion until at least 7 days after each iobenguane dose. Risk X: Avoid combination

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

Lofexidine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine. 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

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: Reduce metoclopramide dose to 5 mg 4 times daily (30 minutes before each meal and at bedtime) and limit the maximum daily dose to 20 mg if combined with strong CYP2D6 inhibitors. 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 (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor therapy

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

PARoxetine: BuPROPion may enhance the adverse/toxic effect of PARoxetine. Specifically, the risk for seizures and serotonin syndrome may be increased. 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

Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination

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

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies. Risk D: Consider therapy modification

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

Sertraline: BuPROPion may enhance the adverse/toxic effect of Sertraline. Specifically, the risk for seizures and serotonin syndrome may be increased. Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Risk X: Avoid combination

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

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

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

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of Tricyclic Antidepressants. Exceptions: Amoxapine; Protriptyline. Risk C: Monitor therapy

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

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

Vilazodone: BuPROPion may enhance the adverse/toxic effect of Vilazodone. Specifically, the risk for seizures and serotonin syndrome may be increased. Risk C: Monitor therapy

Vortioxetine: BuPROPion may enhance the adverse/toxic effect of Vortioxetine. Specifically, the risk for seizures and serotonin syndrome may be increased. 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

Test Interactions

May interfere with urine detection of amphetamine/methamphetamine (false-positive). Decreased prolactin levels.

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).

Advanced Practitioners Physical Assessment/Monitoring

Perform careful cardiovascular, neurologic, and liver function assessments prior to initiating therapy. Monitor blood pressure and LFTs at beginning of therapy and periodically throughout. Monitor for clinical worsening; neuropsychiatric symptoms, such as changes in behavior, hostility, agitation, seizures, paranoia, hallucinations, insomnia, depression, and suicidality, especially at the beginning of therapy or when dose changes occur. Taper dosage slowly when discontinuing. Dosage adjustment indicated with hepatic impairment.

Nursing Physical Assessment/Monitoring

Monitor blood pressure at beginning of therapy and periodically throughout treatment. Monitor mental status for clinical worsening, such as changes in behavior, hostility, agitation, paranoia, hallucinations, depression, and suicidality, especially at the beginning of therapy or when dose changes occur.

Dosage Forms: US

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, 450 mg

Dosage Forms: Canada

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

Tablet Extended Release 12 Hour, Oral, as hydrochloride:

Wellbutrin SR: 150 mg [contains FD&C BLUE #2 ALUMINUM LAKE, FD&C RED #40 ALUMINUM LAKE, POLYSORBATE 80]

Zyban: 150 mg [contains FD&C BLUE #2 ALUMINUM LAKE, FD&C RED #40 ALUMINUM LAKE, POLYSORBATE 80]

Generic: 100 mg, 150 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride:

Wellbutrin XL: 150 mg, 300 mg [contains ALCOHOL, USP]

Generic: 150 mg, 300 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AX12
Generic Available (US)

Yes

Pricing: US

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

150 mg (per each): $1.94 – $3.73

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

100 mg (per each): $1.69 – $1.94

150 mg (per each): $0.70 – $1.94

200 mg (per each): $3.38 – $3.83

Tablet, 12-hour (Wellbutrin SR Oral)

100 mg (per each): $8.31

150 mg (per each): $8.91

200 mg (per each): $16.54

Tablet, 12-hour (Zyban Oral)

150 mg (per each): $4.96

Tablet, 24-hour (Aplenzin Oral)

174 mg (per each): $55.19

348 mg (per each): $72.75

522 mg (per each): $165.56

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

150 mg (per each): $0.52 – $5.22

300 mg (per each): $0.55 – $19.33

450 mg (per each): $16.07 – $16.76

Tablet, 24-hour (Forfivo XL Oral)

450 mg (per each): $17.88

Tablet, 24-hour (Wellbutrin XL Oral)

150 mg (per each): $54.49

300 mg (per each): $71.92

Tablets (buPROPion HCl Oral)

75 mg (per each): $0.64 – $1.55

100 mg (per each): $0.86 – $1.97

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.

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:

Hydrochloride salt: ~21 hours after chronic dosing (± 9 hours); Metabolites (after a single dose): Hydroxybupropion: 20 ± 5 hours; Erythrohydrobupropion: 33 ± 10 hours; Threohydrobupropion: 37 ± 13 hours

Hydrobromide salt: 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; 12-hour extended release (sustained release): Within 3 hours; 24-hour extended release: ~5 hours; 12 hours (fed)

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

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

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Elimination of bupropion and/or major metabolites may be reduced.

Hepatic function impairment: Elimination of hydroxybupropion is reduced in patients with alcoholic liver disease. Bupropion Cmax increased 70%, AUC increased 3-fold, and mean half-life increased to 29 hours in patients with severe hepatic impairment. Mean half-life for active metabolites increased 2- to 5-fold in patients with severe hepatic impairment.

Geriatric: May be at risk of accumulation of bupropion and its metabolites.

Gender: AUC was approximately 13% higher in men.

Local Anesthetic/Vasoconstrictor Precautions

Part of the mechanism of bupropion is to block reuptake of norepinephrine along with dopamine. Because of the potential for norepinephrine elevation within CNS synapses, it is suggested that vasoconstrictor be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes with discontinuation); infrequent occurrence of abnormal taste, oral mucosal ulcers; rare occurrence of stomatitis, tongue edema, gingivitis, glossitis.

Effects on Bleeding

Thrombocytopenia (<1%) as been reported; rare occurrence of gingival hemorrhage.

Index Terms

Budeprion SR; Bupropion HCl; Bupropion Hydrobromide; Bupropion Hydrochloride

FDA Approval Date
December 30, 1985
References

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ACOG, “Committee Opinion No. 471: Smoking Cessation During Pregnancy,” Obstet Gynecol, 2010, 116(5):1241-4.[PubMed 20966731]

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Barrickman LL, Petty PJ, Allen AJ, et al. Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry.1995;34(5):649-657.[PubMed 7775360]

Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14(5):334-385.[PubMed 23879318]

Berle JO, Spigset O. Antidepressant use during breastfeeding. Curr Womens Health Rev. 2011;7(1):28-34.[PubMed 22299006]

Bond DJ, Hadjipavlou G, Lam RW, et al; Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder. Ann Clin Psychiatry. 2012;24(1):23-37.[PubMed 22303520]

Brent D, Bukstein O, Solanto MV. Approach to treating attention deficit hyperactivity disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 19, 2019.

Bukstein O. Pharmacotherapy for attention deficit hyperactivity disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2019.

Bupropion hydrochloride [prescribing information]. Sunrise, FL: Cipla USA Inc; November 2017.

Burke MJ, Preskorn SH. Therapeutic drug monitoring of antidepressants: cost implications and relevance to clinical practice. Clin Pharmacokinet. 1999;37(2):147-165.[PubMed 10496302]

Chaudron LH and Schoenecker CJ, “Bupropion and Breastfeeding: A Case of a Possible Infant Seizure,” J Clin Psychiatry, 2004, 65(6):881-2.[PubMed 15291673]

Cinciripini PM, Robinson JD, Karam-Hage M, et al. Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry. 2013;70(5):522-533.[PubMed 23536105]

Clayton AH, Warnock JK, Kornstein SG, Pinkerton R, Sheldon-Keller A, McGarvey EL. A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry. 2004;65(1):62-67.[PubMed 14744170]

Conners CK, Casat CD, Gualtieri CT, et al. Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1996;35(10):1314-1321.[PubMed 8885585]

Davis MF, Miller HS, and Nolan PE Jr, “Bupropion Levels in Breast Milk for 4 Mother-Infant Pairs: More Answers to Lingering Questions,” J Clin Psychiatry, 2009, 70(2):297-8.[PubMed 19265649]

Earhart AD, Patrikeeva S, Wang X, et al, “Transplacental Transfer and Metabolism of Bupropion,” J Matern Fetal Neonatal Med, 2010, 23(5):409-16.[PubMed 19658039]

Fiore M, Jaen CR, Baker TB, et al, “A Clinical Practice Guideline for Treating Tobacco Use and Dependence: 2008 Update. A U.S. Public Health Service Report,” Am J Prev Med, 2008, 35(2):158-76. https://www.ahrq.gov/sites/default/files/wysiwyg/professionals/clinicians-providers/guidelines-recommendations/tobacco/clinicians/update/treating_tobacco_use08.pdf.[PubMed 18617085]

Forfivo XL (bupropion hydrochloride) [prescribing information]. Pine Brook, NJ: Almatica Pharma Inc; May 2017.

Goodnick PJ. Blood levels and acute response to bupropion. Am J Psychiatry. 1992;149(3):399-400.[PubMed 1536282]

Grossman F, Potter WZ, Brown EA, Maislin G. A double-blind study comparing idazoxan and bupropion in bipolar depressed patients. J Affect Disord. 1999;56(2-3):237-243.[PubMed 10701483]

Grunze H, Vieta E, Goodwin GM; WFSBP Task Force on Treatment Guidelines for Bipolar Disorder. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry. 2010;11(2):81-109. doi: 10.3109/15622970903555881.[PubMed 20148751]

Hale TW, Kendall-Tackett K, Cong Z, et al, “Discontinuation Syndrome in Newborns Whose Mothers Took Antidepressants While Pregnant or Breastfeeding,” Breastfeed Med, 2010, 5(6):283-8.[PubMed 20807106]

Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031. doi: 10.1002/14651858.CD000031.pub4.[PubMed 24402784]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Jafarinia M, Mohammadi MR, Modabbernia A, et al. Bupropion versus methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder: randomized double-blind study. Hum Psychopharmacol. 2012;27(4):411-418. doi: 10.1002/hup.2242.[PubMed 22806822]

Laizure SC, DeVane CL, Stewart JT, et al, “Pharmacokinetics of Bupropion and Its Major Basic Metabolites in Normal Subjects After a Single Dose,” Clin Pharmacol Ther, 1985, 38(5):586-9.[PubMed 3931955]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Li DJ, Tseng PT, Chen YW, Wu CK, Lin PY. Significant treatment effect of bupropion in patients with bipolar disorder but similar phase-shifting rate as other antidepressants: a meta-analysis following the PRISMA guidelines. Medicine (Baltimore). 2016;95(13):e3165. doi: 10.1097/MD.0000000000003165.[PubMed 27043678]

Maneeton N, Maneeton B, Srisurapanont M, Martin SD. Bupropion for adults with attention-deficit hyperactivity disorder: meta-analysis of randomized, placebo-controlled trials. Psychiatry Clin Neurosci. 2011;65(7):611-617. doi: 10.1111/j.1440-1819.2011.02264.x.[PubMed 22176279]

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH. Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study. Bipolar Disord. 2002;4(3):207-213.[PubMed 12180276]

Nelson JC and Devanand DP, “A Systematic Review and Meta-Analysis of Placebo-Controlled Antidepressant Studies in People With Depression and Dementia,” J Am Geriatr Soc, 2011, 59(4):577-85.[PubMed 21453380]

Neuman G, Colantonio D, Delaney S, Szynkaruk M, Ito S. Bupropion and escitalopram during lactation. Ann Pharmacother. 2014;48(7):928-931.[PubMed 24732787]

Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921.[PubMed 17581453]

Preskorn SH. Antidepressant response and plasma concentrations of bupropion. J Clin Psychiatry. 1983;44(5 Pt 2):137-139.[PubMed 6406443]

Reimherr FW, Hedges DW, Strong RE, Marchant BK, Williams ED. Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. Neuropsychiatr Dis Treat. 2005;1(3):245-251.[PubMed 18568102]

Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-809.[PubMed 23979084]

Safarinejad MR. Reversal of SSRI-induced female sexual dysfunction by adjunctive bupropion in menstruating women: a double-blind, placebo-controlled and randomized study. J Psychopharmacol. 2011;25(3):370-378. doi: 10.1177/0269881109351966.[PubMed 20080928]

Siu AL; US Preventive Services Task Force. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(8):622-634. doi: 10.7326/M15-2023.[PubMed 26389730]

Sriraman NK, Melvin K, Meltzer-Brody S. ABM clinical protocol #18: use of antidepressants in breastfeeding mothers. Breastfeed Med. 2015;10(6):290-299.[PubMed 26204124]

Vetter VL, Elia J, Erickson CH, et al; American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee; American Heart Association Council on Cardiovascular Nursing. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder [corrected]: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation. 2008;117(18):2407-2423.[PubMed 18427125]

Wellbutrin SR (bupropion hydrochloride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; May 2017.

Wellbutrin SR (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; March 2017.

Wellbutrin XL (bupropion hydrochloride) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; May 2017.

Wellbutrin XL (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; March 2017.

Wilens TE, Haight BR, Horrigan JP, et al. Bupropion XL in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled study. Biol Psychiatry. 2005;57(7):793-801.[PubMed 15820237]

Wilens TE, Spencer TJ, Biederman J, et al. A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001;158(2):282-288.[PubMed 11156812]

Yonkers KA, Wisner KL, Stewart DE, et al, “The Management of Depression During Pregnancy: A Report From the American Psychiatric Association and the American College of Obstetricians and Gynecologists,” Obstet Gynecol, 2009, 114(3):703-13.[PubMed 19701065]

Zyban (bupropion hydrochloride) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; May 2017.

Zyban (bupropion hydrochloride) [product monograph]. Laval, Quebec, Canada: Valeant Canada LP; July 2016.

Brand Names: International

Abstain SR (EG); Betetrim (TW); Bupep SR (IN); Buprotrin (TW); Buxon (CL); Deppreo (VN); Elontril (EE, ES, HU, LT, RO, SK); Fumipan (EG); Funnix (TW); Le Fu Ting (CN); Nicopion (KR); Nicostop (VN); Odranal (AR, CO); Prewell (TW); Prexaton (AU); Quomen (TH); Vixadep (EG); Wellbutrin (MX, PE, PY, TW, VE); Wellbutrin Retard (IS, SK); Wellbutrin SR (AR, BB, BM, BS, CL, CR, DO, EC, GT, HK, HN, HU, JM, KR, LV, MY, 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); Wellinta (EG); 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); Zyban LP (FR); Zyban SR (BH, KW, QA, SG); Zyban Sustained Release (AU); Zylexx SR (PK); Zyntabac (ES)

Bupropion (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(byoo PROE pee on)

Brand Names: US

Aplenzin; Buproban [DSC]; Forfivo XL; Wellbutrin SR; Wellbutrin XL; Wellbutrin [DSC]; Zyban

Brand Names: Canada

Wellbutrin SR; Wellbutrin XL; Zyban

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat seasonal affective disorder (SAD).
  • It is used to help you stop smoking.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to bupropion or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have ever had seizures.
  • If you drink a lot of alcohol and you stop drinking all of a sudden.
  • If you use certain other drugs like drugs for seizures or anxiety and you stop using them all of a sudden.
  • If you have ever had an eating problem like anorexia or bulimia.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you are taking another drug that has the same drug in it.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • For all patients taking this drug:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this drug affects you.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • High blood pressure has happened with this drug. Have your blood pressure checked as you have been told by your doctor.
  • This drug may raise the chance of seizures. The chance may be higher in people who have certain health problems, use certain other drugs, or drink a lot of alcohol. Talk to your doctor to see if you have a greater chance of seizures while taking this drug.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • It may take several weeks to see the full effects.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this drug.
  • This drug is not approved for use in children. Talk with the doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • If you smoke:
  • Not all products are approved for use to help stop smoking. Talk with the doctor to make sure that you have the right product.
  • New or worse mental, mood, or behavior problems have happened when bupropion has been used to stop smoking. These problems include thoughts of suicide or killing someone else, depression, forceful actions, fury, anxiety, and anger. These problems have happened in people with and without a history of mental or mood problems. Talk with the doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Change in how you act.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • If seizures are new or worse after starting this drug.
  • A big weight gain or loss.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Swelling.
  • Shortness of breath.
  • Change in hearing.
  • Ringing in ears.
  • Passing urine more often.
  • Swollen gland.
  • Trouble moving around.
  • Very bad muscle or joint pain.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All products:
  • Dizziness.
  • Headache.
  • Belly pain.
  • Shakiness.
  • Feeling nervous and excitable.
  • Strange or odd dreams.
  • Upset stomach or throwing up.
  • Constipation.
  • Gas.
  • Dry mouth.
  • Not able to sleep.
  • Muscle or joint pain.
  • Nose or throat irritation.
  • Sweating a lot.
  • Not hungry.
  • A change in weight without trying.
  • Extended-release tablets:
  • For some brands, you may see the tablet shell in your stool. For these brands, this is normal and not a cause for concern. If you have questions, talk with your doctor.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • For all patients taking this drug:
  • Do not take this drug more often than you are told. This may raise the risk of seizures. Be sure you know how far apart to take your doses.
  • Take in the morning if taking once a day.
  • Take with or without food.
  • If you are not able to sleep, do not take this drug too close to bedtime. Talk with your doctor.
  • Swallow whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • If you have trouble swallowing, talk with your doctor.
  • For stopping smoking:
  • You may take this drug for 1 week before you stop smoking.
  • Nicotine products and counseling may be used at the same time for best results.
  • If you have not been able to quit smoking after taking this drug for 12 weeks, talk with your doctor.
  • You may have signs of nicotine withdrawal when you try to quit smoking even when using drugs like this one to help you quit smoking. There are many signs of nicotine withdrawal. Rarely depression and suicidal thoughts have happened in people trying to quit smoking. Talk with your doctor.
What do I do if I miss a dose?
  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Bupropion (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(byoo PROE pee on)

Brand Names: US

Aplenzin; Buproban [DSC]; Forfivo XL; Wellbutrin SR; Wellbutrin XL; Wellbutrin [DSC]; Zyban

Brand Names: Canada

Wellbutrin SR; Wellbutrin XL; Zyban

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat seasonal affective disorder (SAD).
  • It may be given to your child for other reasons. Talk with the doctor.
  • For stopping smoking:
  • If your child has been given this form of this drug, talk with the doctor for information about the benefits and risks. Talk with the doctor if you have questions or concerns about giving this drug to your child.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has ever had seizures.
  • If your child drinks a lot of alcohol and stops drinking all of a sudden.
  • If your child uses certain other drugs or natural products that may slow your child’s actions (like drugs for seizures or anxiety) and your child stops using them all of a sudden.
  • If your child has ever had an eating problem like anorexia or bulimia.
  • If your child has any of these health problems: Kidney disease or liver disease.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child is taking any of these drugs: Linezolid or methylene blue.
  • If your child is taking another drug that has the same drug in it.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • For all patients taking this drug:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • High blood pressure has happened with this drug. Have your child’s blood pressure checked as you have been told by the doctor.
  • This drug may raise the chance of seizures. The chance may be higher in people who have certain health problems, use certain other drugs, or drink a lot of alcohol. Talk to the doctor to see if your child has a greater chance of seizures while taking this drug.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • It may take several weeks to see the full effects.
  • Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
  • If your child is taking digoxin, talk with your child’s doctor. Your child may need to have blood work checked more closely while taking it with this drug.
  • This drug is not approved for use in children. Talk with the doctor.
  • If your child is pregnant or breast-feeding a baby:
  • Talk with the doctor if your child is pregnant, becomes pregnant, or is breast-feeding a baby. You will need to talk about the benefits and risks to your child and the baby.
  • If your child smokes:
  • Not all products are approved for use to help stop smoking. Talk with the doctor to make sure that you have the right product.
  • New or worse mental, mood, or behavior problems have happened when bupropion has been used to stop smoking. These problems include thoughts of suicide or killing someone else, depression, forceful actions, fury, anxiety, and anger. These problems have happened in people with and without a history of mental or mood problems. Talk with the doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Change in the way your child acts.
  • Feeling confused.
  • Hallucinations (seeing or hearing things that are not there).
  • If seizures are new or worse after starting this drug.
  • A big weight gain or loss.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Swelling.
  • Shortness of breath.
  • Change in hearing.
  • Ringing in ears.
  • Passing urine more often.
  • Swollen gland.
  • Trouble moving around.
  • Very bad muscle or joint pain.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All products:
  • Dizziness.
  • Headache.
  • Belly pain.
  • Shakiness.
  • Feeling nervous and excitable.
  • Strange or odd dreams.
  • Upset stomach or throwing up.
  • Constipation.
  • Gas.
  • Dry mouth.
  • Not able to sleep.
  • Muscle or joint pain.
  • Nose or throat irritation.
  • Sweating a lot.
  • Not hungry.
  • A change in weight without trying.
  • Extended-release tablets:
  • For some brands, you or your child may see the tablet shell in your child’s stool. For these brands, this is normal and not a cause for concern. If you have questions, talk with the doctor.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Give this drug at the same time of day.
  • Do not give this drug more often than told. This may raise the risk of seizures. Be sure you know how far apart to give your child’s doses.
  • Give in the morning if giving once a day.
  • Give this drug with or without food.
  • If your child is not able to sleep, do not give this drug too close to bedtime. Talk with the doctor.
  • Have your child swallow tablet whole. Do not let your child chew, break, or crush.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • If your child has trouble swallowing, talk with the doctor.
What do I do if my child misses a dose?
  • Skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.