Version July 2025
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 over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Bupropion is not approved for use in pediatric patients.
Dosage guidance:
Dosing: 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 unipolar major depressive disorder or as an alternative agent for patients with a history of substance use disorders (Ref).
12-hour extended release (sustained release): Oral: Initial: 100 mg once daily in the morning. After ≥1 week, based on response and tolerability, increase to 100 mg twice daily. May increase, based on response and tolerability, in 100 mg/day increments at intervals of 3 to 4 weeks up to 200 mg twice daily. Usual maintenance dosage: 100 to 150 mg twice daily. Use twice daily divided doses for doses ≥200 mg/day (Ref).
24-hour extended release: Oral: Initial: 150 mg once daily in the morning for ≥1 week; increase to usual maintenance dosage of 300 mg once daily for 3 weeks; may further increase dose based on response and tolerability up to 450 mg once daily (Ref).
Bipolar disorder, depressive episode (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) (Ref).
Major depressive disorder (unipolar):
Note: 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 (Ref).
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 once 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:
Hydrochloride salt: Oral: Initial: 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: Oral: Initial: 174 mg once daily in the morning; may increase as early as day 4 of dosing to 348 mg once daily (target dose). Maximum dose: 522 mg once daily.
Methamphetamine use disorder (off-label use):
24-hour extended release: Hydrochloride salt: Oral: Initial: 150 mg once daily (in combination with IM naltrexone); increase based on response and tolerability in 150 mg increments every 1 to 2 days up to a target dose of 300 to 450 mg once daily (Ref).
Seasonal affective disorder:
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.
24-hour extended release:
Hydrochloride salt: Oral: 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: Oral: Initial: 174 mg once daily in the morning; if tolerated, may increase after 7 days to 348 mg once daily in the morning.
Sexual dysfunction associated with selective serotonin reuptake inhibitors (SSRIs) (off-label use):
Note: May add on to SSRI or switch to bupropion for mitigating sexual adverse effects. Prior to adding or switching, may trial watchful waiting for limited time (eg, 2 to 8 weeks), as treatment-onset sexual dysfunction may remit spontaneously (Ref).
Augmentation:
12-hour extended release (sustained release): Oral: Initial: 150 mg once daily for 2 to 4 weeks; then increase to 150 mg twice daily based on response and tolerability. After an additional 2 to 4 weeks, if needed, may further increase to a maximum of 200 mg twice daily (Ref). May also increase initial dose sooner (eg, after 3 days) to 150 mg twice daily if needed and tolerated (Ref).
24-hour extended release: Oral: Initial: 150 mg once daily for 2 to 4 weeks; then increase to 300 mg once daily based on response and tolerability. After an additional 2 to 4 weeks, if needed, may further increase to a maximum of 450 mg once daily (Ref). May also increase initial dose sooner (eg, after 4 days) to 300 mg once daily if needed and tolerated (Ref).
Switching antidepressant to bupropion (monotherapy): Oral: Switch from serotonin reuptake inhibitor using an appropriate schedule (eg, cross taper over 1 to 2 weeks). Initiate and titrate bupropion to a therapeutic dose appropriate for indication and based upon response (Ref).
Smoking cessation:
Note: May be used as monotherapy or in combination with nicotine replacement therapy (Ref). 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, continue treatment for at least 12 weeks. May consider maintenance therapy based on individual patient risk:benefit; evidence suggests relapse prevention benefits with continuing therapy for up to 1 year. 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 (Ref).
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 (Ref).
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.
Discontinuation of therapy: When discontinuing antidepressant therapy that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 weeks) to allow for the detection of reemerging symptoms. For brief treatment (eg, 2 or 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering. Withdrawal symptoms resulting from abrupt discontinuation are unlikely because bupropion has minimal serotonergic activity (Ref).
Switching antidepressants:Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 selective serotonin reuptake inhibitors), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from a monoamine oxidase inhibitor:
Allow 14 days to elapse between discontinuing a monoamine oxidase inhibitor (MAOI) initiation of bupropion.
Allow 14 days to elapse between discontinuing bupropion and initiation of an MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Limited pharmacokinetic data available for patients with kidney impairment. Accumulation of bupropion and its active metabolites are likely to occur if using unadjusted doses in patients with chronic kidney disease or end-stage kidney disease (Ref).
Altered kidney function:
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 15 to 60 mL/minute: Use with caution; consider a maximum daily dose of 150 mg/day (Ref).
CrCl <15 mL/minute: Use of alternative agent may be preferred. Use with caution; to limit accumulation of active metabolites, initiate therapy at 100 mg every 48 hours or 150 mg every 72 hours (Ref). Titrate gradually based on tolerability and response to a maximum daily dose of 150 mg/day (Ref).
Hemodialysis, intermittent (thrice weekly): Minimally dialyzable (13%); major active metabolite (hydroxybupropion) is not dialyzable (Ref):
Use of alternative agent may be preferred. Use with caution; to limit accumulation of active metabolites, initiate therapy at 100 mg every 48 hours or 150 mg every 72 hours (Ref). Titrate gradually based on tolerability and response to a maximum daily dose of 150 mg/day (Ref).
Peritoneal dialysis: Not likely to be dialyzable (Ref):
Use of alternative agent may be preferred. Use with caution; to limit accumulation of active metabolites, initiate therapy at 100 mg every 48 hours or 150 mg every 72 hours (Ref). Titrate gradually based on tolerability and response to a maximum daily dose of 150 mg/day (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Bupropion is extensively metabolized to active metabolites in the liver. In severe liver impairment, bupropion exposure and half-life may be significantly increased (Ref).
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A and B: Immediate release, 12-hour extended release (sustained release), or 24-hour extended release: Oral: Initial: Administer 50% of the usual indication-specific dose and/or extend the usual frequency (eg, if the usual recommended initial dose for the immediate release is 100 mg twice daily, then reduce dose to 100 mg once daily; or if the usual recommended initial dose for the 12-hour extended release [sustained release] is 150 mg once daily, then extend the interval [ie, administer 150 mg every 48 hours]); may titrate no more frequently than every 14 days based on tolerability and response, not to exceed the indication-specific maximum recommended dose (Ref).
Child-Turcotte-Pugh class C: Note: Not recommended for smoking cessation or selective serotonin reuptake inhibitor–induced sexual dysfunction; alternative agents are preferred (Ref). If alternative agents are not clinically appropriate, may use bupropion with extreme caution.
Immediate release: Oral: Initial: 75 mg every other day; may titrate no more frequently than every 30 days based on tolerability and response (Ref); maximum dose: 75 mg once daily.
12-hour extended release (sustained release): Oral: Note: Tolerability must be established with the IR formulation prior to converting to the 12-hour ER (sustained release) formulation (Ref). Maximum dose: 100 mg once daily or ≤150 mg every other day.
24-hour extended release: Oral: Note: Tolerability must be established with the IR formulation prior to converting to a 24-hour ER formulation (Ref). Maximum dose: 150 mg (hydrochloride salt) or 174 mg (hydrobromide salt) every other day.
Liver impairment developing in patient already receiving bupropion:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A or B: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class C: No dosage adjustment necessary; however, use with caution and only under the guidance of an appropriate expert (Ref).
Refer to adult dosing; use with caution.
(For additional information see "Bupropion: Pediatric drug information")
Dosage guidance:
Dosing: Use extra precaution with selection of dosage forms: 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 (ADHD): Limited data available:
Note: Bupropion is not recommended as first-line therapy in the management of ADHD in pediatric patients (Ref). In comparative trials with methylphenidate, a small volume of evidence suggests bupropion may have similar efficacy (Ref); however, the role of bupropion has not been defined.
Children ≥6 years and Adolescents: Oral:
Immediate release, hydrochloride salts: Initial: 1.5 to 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 (Ref). Note: When determining initial dose, assess available dosage forms (eg, 1/2 of 75 mg tablet may be lowest achievable dose).
12-hour sustained release (eg, Wellbutrin SR) and 24-hour extended release (eg, Wellbutrin XL), hydrochloride salts: In patients able to swallow tablets whole: 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). In pediatric efficacy trials, mean final effective dose ranges for sustained-release formulations were similar to immediate release (Ref).
Depression, refractory: Limited data available:
Note: In the management of depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, bupropion is not recommended as first-line therapy (Ref). Some suggest it may be beneficial in patients with comorbid ADHD (Ref). Treatment should be periodically evaluated at appropriate intervals to ensure lowest effective dose is used.
Immediate release, hydrochloride salt: Children ≥8 years and Adolescents: Oral: Initial: 37.5 mg twice daily; titrate to response; titration intervals of every 1 to 2 weeks have been suggested (Ref); usual reported dosage range: 100 to 300 mg/day in divided doses; maximum reported daily dose: 400 mg/day (Ref).
12-hour sustained release, hydrochloride salt (eg, Wellbutrin SR): Children ≥11 years and Adolescents: Oral: Initial: 2 mg/kg once daily 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 (Ref).
24-hour extended release, hydrochloride salt (eg, 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 8 patients with depression weighing ≥30 kg (Ref); doses as high as 400 mg/day have been reported (Ref); 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: 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; dosing based on a short-term efficacy trial of 104 adolescents who received therapy for 7 weeks with cessation counseling (Ref); however, long-term efficacy (6-month abstinence data point) has not been reported (Ref).
Dosing conversion between hydrochloride salt immediate release, 12-hour sustained release (eg, Wellbutrin SR), and 24-hour extended release (eg, 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: Consider planning antidepressant discontinuation for lower-stress times, recognizing nonillness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested; use with caution.
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.
Antidepressants (especially when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients initially diagnosed with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder initially present with a major depression episode (Ref). Some studies report a lower risk of manic switching with bupropion versus other antidepressants, but these studies have been small and lacked statistical power to determine true differences among agents (Ref).
Mechanism: Non-dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref). The noradrenergic pharmacology of bupropion leading to stimulatory adverse reactions may play a role (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy but not thereafter (up to 4.6 years) (Ref). Can present as new-onset mania or cycle acceleration of existing bipolar disorder (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Female sex (Ref)
Bupropion can cause CNS stimulation in patients, including increased energy, insomnia, agitation, and nervousness, and, in more significant cases, anxiety or panic. On rare occasions, more significant neuropsychiatric effects, including changes in thinking, paranoid ideation, delusion, hallucination, psychosis, suicidal ideation, and homicidal ideation, may occur (Ref).
Mechanism: Dose-related; bupropion is chemically related to amphetamines. Inhibition of norepinephrine reuptake can lead to stimulatory effects and inhibition of dopamine reuptake can lead to alterations in thinking and perception (Ref). Bupropion also inhibits nicotinic acetylcholine receptors (Ref). In patients taking bupropion for smoking cessation, some cases occurred during treatment discontinuation and may reflect symptoms resulting from nicotine withdrawal.
Onset: Varied; may occur shortly after initiation or dose increases.
Risk factors:
• Concurrent substance use (especially stimulants) (Ref)
• Higher doses (Ref)
• History of psychiatric disease (possible risk factor) (Note: Cases have occurred in patients with and without preexisting psychiatric disease who are taking bupropion for smoking cessation)
• Misuse/overdose (Ref)
Bupropion is associated with an increased risk of acute angle-closure glaucoma (AACG) in a case-controlled study, particularly in adults <50 years of age (Ref). AACG may cause symptoms, including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). Of note, some studies suggest that bupropion may reduce the risk of open-angle glaucoma (Ref).
Mechanism: Unclear; hypothesized that bupropion may cause choroidal effusion and pupil dilation (Ref).
Risk factors:
Specific to bupropion:
• Adults <50 years of age (Ref)
Additional risk factors for AACG in general:
• Adults ≥50 years of age (slight increase) (Ref)
• Females (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Concurrent use of medications that increase risk of AACG (eg, topiramate) (Ref)
• Asian or Inuit descent (Ref)
Bupropion is associated with dose-related risk of seizure. Seizure risk with bupropion may be the greatest among antidepressants (Ref).
Mechanism: Dose-related; hypothesized to be related to increasing concentrations of sympathomimetic amines, causing activation of neuronal pathways in the hypothalamus (Ref).
Risk factors:
• Abrupt discontinuation of ethanol, benzodiazepines, barbiturates, or antiseizure drugs
• Concurrent electrolyte/metabolic disturbances (eg, hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia)
• Concurrent use of drugs that lower the seizure threshold (eg, antipsychotics, antidepressants, theophylline, systemic corticosteroids, stimulants [including cocaine], anorexiants, hypoglycemic agents)
• Conditions with high seizure risk (eg, arteriovenous malformation, severe head injury, severe stroke, CNS tumor, CNS infection)
• Excessive use of ethanol, benzodiazepines, sedative/hypnotics, or opioids
• Higher doses/overdoses (especially >400 mg/day)
• History of anorexia or bulimia
• History of seizures
• Use of immediate-release formulations (Ref)
Bupropion use is associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults >24 years of age, short-term studies did not show an increased risk of suicidal thinking and behavior, and in older adults (≥65 years of age), a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs. Overdose with bupropion among adolescents was found to have more significant toxicological effects, including death, vs selective serotonin reuptake inhibitors (SSRI) overdoses (Ref).
Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses and another suggests that antidepressants may produce a worsening of depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide is associated with major depression and may persist until remission occurs)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Tachycardia (11%)
Dermatologic: Diaphoresis (5% to 22%)
Endocrine & metabolic: Weight loss (14% to 28%)
Gastrointestinal: Constipation (8% to 26%), nausea (9% to 18%), nausea and vomiting (23%), xerostomia (10% to 28%)
Nervous system: Agitation (2% to 32%) (table 1), dizziness (6% to 22%), headache (≤34%), insomnia (11% to 40%) (table 2), migraine (≤26%), tremor (1% to 21%)
|
Drug (Bupropion) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bupropion) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
32% |
22% |
N/A |
Immediate-release tablets |
Major depressive disorder |
323 |
185 |
|
9% |
2% |
400 mg/day |
Sustained-release tablets |
Major depressive disorder |
114 |
385 |
|
3% |
2% |
300 mg/day |
Sustained-release tablets |
Major depressive disorder |
376 |
385 |
|
2% |
<1% |
300 mg/day |
Extended-release tablets |
Seasonal affective disorder |
537 |
511 |
|
Drug (Bupropion) |
Comparator (Nicotine transdermal system) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bupropion) |
Number of Patients (Nicotine transdermal system) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
40% |
28% |
18% |
300 mg/day |
Sustained-release tablets |
Aid to smoking cessation treatment |
243 |
243 |
159 |
|
31% |
N/A |
21% |
100 to 300 mg/day |
Sustained-release tablets |
Aid to smoking cessation treatment |
461 |
N/A |
150 |
|
19% |
N/A |
16% |
N/A |
Immediate-release tablets |
Major depressive disorder |
323 |
N/A |
185 |
|
16% |
N/A |
6% |
400 mg/day |
Sustained-release tablets |
Major depressive disorder |
114 |
N/A |
385 |
|
11% |
N/A |
6% |
300 mg/day |
Sustained-release tablets |
Major depressive disorder |
376 |
N/A |
385 |
|
20% |
N/A |
13% |
300 mg/day |
Extended-release tablets |
Seasonal affective disorder |
537 |
N/A |
511 |
Ophthalmic: Blurred vision (≤15%)
Respiratory: Nasopharyngitis (13%), pharyngitis (3% to 11%), rhinitis (12%)
1% to 10%:
Cardiovascular: Cardiac arrhythmia (5%), chest pain (3% to 4%), ECG abnormality (≤1%), edema, flushing (1% to 4%), hypertension (1% to 4%; including severe hypertension), hypotension (3%), orthostatic hypotension (≤1%), palpitations (2% to 6%), peripheral edema (≤1%), syncope (1%), vasodilation (≤1%)
Dermatologic: Alopecia (≤1%), ecchymoses (≤1%), pruritus (2% to 4%), skin photosensitivity (≤1%), skin rash (3% to 8%), urticaria (1% to 2%), xeroderma (2%)
Endocrine & metabolic: Decreased libido (3%), gynecomastia (≤1%), hot flash (1% to 3%), increased libido, increased thirst (≤1%), menstrual disease (5%), weight gain (9%)
Gastrointestinal: Abdominal pain (2% to 9%), anorexia (1% to 5%), bruxism (≤1%), decreased appetite (4%), diarrhea (4% to 7%), dysgeusia (2% to 4%), dyspepsia (3%), dysphagia (2%), flatulence (6%), gastroesophageal reflux disease (≤1%), gingivitis (≤1%), increased appetite (2% to 4%), oral mucosa ulcer (2%), sialorrhea (≤1%), stomatitis, vomiting (4%)
Genitourinary: Delayed ejaculation (≤1%), dysmenorrhea (2%), erectile dysfunction (≤1%), nocturia, painful erection (≤1%), prostatic disease (≤1%), testicular swelling (≤1%), urinary frequency (3% to 5%), urinary tract infection (1%), urinary urgency (2%), vaginal hemorrhage (2%)
Hepatic: Hepatic injury (≤1%), jaundice (≤1%)
Hypersensitivity: Facial edema (≤1%), hypersensitivity reaction (1%)
Infection: Infection (8% to 9%)
Nervous system: Abnormal dreams (3% to 5%), abnormal sensory symptoms (4%), akathisia (2%), anxiety (3% to 8%) (table 3), asthenia (4%), ataxia, changes in thinking (1%) (table 4), cerebrovascular accident (≤1%), chills (≤1%), confusion (8%), decreased sexual activity, depersonalization (≤1%), depression, drowsiness (2% to 3%), dysarthria (≤1%), dysphoria (≤1%), dystonia, emotional lability (≤1%), euphoria (1%), formal thought disorder (≤1%), hallucination, hostility (6%), hypertonia (≤1%), hypoesthesia (≤1%), hypomania, irritability (3%), jitteriness (3%), lack of concentration (9%), mania, memory impairment (3%), myoclonus, nervousness (4% to 5%) (table 5), pain (3%), paranoid ideation (≤1%), paresthesia (1% to 2%), psychosis (≤1%), seizure, sleep disorder (4%), suicidal ideation (≤1%), twitching (1% to 2%), vertigo (≤1%)
|
Drug (Bupropion) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bupropion) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
1% |
0% |
100 to 300 mg/day |
Sustained-release tablets |
Aid to smoking cessation treatment |
461 |
150 |
|
Drug (Bupropion) |
Comparator (Nicotine transdermal system) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bupropion) |
Number of Patients (Nicotine transdermal system) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
8% |
6% |
6% |
300 mg/day |
Sustained-release tablets |
Aid to smoking cessation treatment |
243 |
243 |
159 |
|
6% |
N/A |
3% |
400 mg/day |
Sustained-release tablets |
Major depressive disorder |
114 |
N/A |
385 |
|
5% |
N/A |
3% |
300 mg/day |
Sustained-release tablets |
Major depressive disorder |
376 |
N/A |
385 |
|
3% |
N/A |
1% |
N/A |
Immediate-release tablets |
Major depressive disorder |
323 |
N/A |
185 |
|
7% |
N/A |
5% |
300 mg/day |
Extended-release tablets |
Seasonal affective disorder |
537 |
N/A |
511 |
|
Drug (Bupropion) |
Comparator (Nicotine transdermal system) |
Placebo |
Dose |
Dosage Form |
Indication |
Number of Patients (Bupropion) |
Number of Patients (Nicotine transdermal system) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|---|
|
4% |
<1% |
2% |
300 mg/day |
Sustained-release tablets |
Aid to smoking cessation treatment |
243 |
243 |
159 |
|
5% |
N/A |
3% |
300 mg/day |
Sustained-release tablets |
Major depressive disorder |
376 |
N/A |
385 |
|
3% |
N/A |
3% |
400 mg/day |
Sustained-release tablets |
Major depressive disorder |
114 |
N/A |
385 |
Neuromuscular & skeletal: Arthralgia (4% to 5%), arthritis (2%), dyskinesia, hyperkinetic muscle activity (≤1%), limb pain (3%), lower limb cramp (≤1%), myalgia (2% to 6%), neck pain (2%)
Ophthalmic: Accommodation disturbance (≤1%), diplopia (≤3%), dry eye syndrome (≤1%), mydriasis (≤1%)
Otic: Auditory disturbance (5%), tinnitus (1% to 6%)
Renal: Polyuria (≤1%)
Respiratory: Bronchitis (2%), cough (2% to 4%), dyspnea (≤1%), epistaxis (2%), flu-like symptoms, sinusitis (2% to 5%), upper respiratory infection (9%)
Miscellaneous: Fever (≤2%)
<1%:
Cardiovascular: Acute myocardial infarction
Gastrointestinal: Intestinal perforation
Genitourinary: Glycosuria, urinary incontinence
Hypersensitivity: Tongue edema
Nervous system: Abnormal electroencephalogram, amnesia, derealization, disturbance in attention, malaise
Respiratory: Bronchospasm
Frequency not defined: Nervous system: Suicidal tendencies
Postmarketing:
Cardiovascular: Complete atrioventricular block, ECG abnormality (Brugada pattern/syndrome), extrasystoles, phlebitis, pulmonary embolism
Dermatologic: Acute generalized exanthematous pustulosis (Ref), cutaneous lupus erythematosus (Ref), erythema multiforme (Ref), exfoliative dermatitis, maculopapular rash, Stevens-Johnson syndrome (Ref)
Endocrine & metabolic: Hirsutism, hyperglycemia, hypoglycemia, hyponatremia (Ref), SIADH
Gastrointestinal: Abnormal stools, colitis, esophagitis, gastric ulcer, gastrointestinal hemorrhage, gingival hemorrhage, glossitis, pancreatitis
Genitourinary: Cystitis, dyspareunia, dysuria, ejaculatory disorder, salpingitis, urinary retention, vaginitis
Hematologic & oncologic: Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, thrombocytopenia
Hepatic: Hepatitis (Ref)
Hypersensitivity: Anaphylactic shock, anaphylaxis (Ref), angioedema (Ref), drug reaction with eosinophilia and systemic symptoms, nonimmune anaphylaxis, serum sickness-like reaction (Ref), type IV hypersensitivity reaction
Nervous system: Aggressive behavior, akinesia, aphasia, delirium (Ref), delusion, extrapyramidal reaction, homicidal ideation, myasthenia, neuralgia, neuropathy, panic (Ref), parkinsonism (Ref), restlessness, tardive dyskinesia (Ref)
Neuromuscular & skeletal: Hypokinesia, muscle rigidity, musculoskeletal chest pain, rhabdomyolysis (Ref), subacute cutaneous lupus erythematosus (Ref)
Ophthalmic: Angle-closure glaucoma (Ref), increased intraocular pressure
Otic: Deafness
Respiratory: Pneumonia
Hypersensitivity to bupropion or any component of the formulation (anaphylaxis, Stevens-Johnson syndrome); seizure disorder; current or history of anorexia nervosa/bulimia; patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiseizure drugs; use of monoamine oxidase inhibitors (MAOIs) (concurrently or within 14 days of discontinuing either bupropion or the MAOI); initiation of bupropion in a patient receiving linezolid or IV methylene blue.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Concerns related to adverse effects:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. A small pharmacokinetic study showed an approximate decrease in bupropion exposure of 50% up to 1 year after Roux-en-Y gastric bypass (Puris 2019). Bupropion has been used to augment weight loss after bariatric surgery in patients in whom weight loss goals have not been met, or who regain weight (Stanford 2017). Although no safety concerns were identified with bupropion use for weight loss after bariatric surgery, other weight loss medications appear more effective (Stanford 2017). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• 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).
• Hypertension: May elevate BP and cause hypertension. Events have been observed in patients with or without evidence of preexisting hypertension.
• Weight loss: May cause weight loss; use caution in patients where weight loss is not desirable.
Disease-related concerns:
• 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 caution in patients with hepatic impairment and use extreme caution in patients with severe hepatic cirrhosis; plasma concentrations are increased. Use caution in patients with hepatic encephalopathy due to the risk of neurocognitive effects (Mauri 2014; Mullish 2014). 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.
Special populations:
• Older adult: Use with caution in elderly patients; may be at greater risk of drug accumulation during chronic dosing.
Dosage form specific issues:
• 24-hour ER 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: May increase the risks associated with electroconvulsive therapy (ECT); consider discontinuing, when possible, prior to ECT treatment (APA 2010).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 75 mg, 100 mg
Tablet Extended Release 12 Hour, Oral, as hydrochloride:
Wellbutrin SR: 100 mg, 150 mg, 200 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
Yes
Tablet, 12-hour (buPROPion HCl ER (Smoking Det) Oral)
150 mg (per each): $1.94
Tablet, 12-hour (buPROPion HCl ER (SR) Oral)
100 mg (per each): $0.27 - $1.69
150 mg (per each): $0.31 - $1.94
200 mg (per each): $0.56 - $3.83
Tablet, 12-hour (Wellbutrin SR Oral)
100 mg (per each): $8.82
150 mg (per each): $9.45
200 mg (per each): $17.54
Tablet, 24-hour (Aplenzin Oral)
174 mg (per each): $88.92
348 mg (per each): $117.22
522 mg (per each): $266.77
Tablet, 24-hour (buPROPion HCl ER (XL) Oral)
150 mg (per each): $0.22 - $5.22
300 mg (per each): $0.31 - $6.30
450 mg (per each): $16.07 - $16.76
Tablet, 24-hour (Forfivo XL Oral)
450 mg (per each): $18.77
Tablet, 24-hour (Wellbutrin XL Oral)
150 mg (per each): $87.80
300 mg (per each): $115.89
Tablets (buPROPion HCl Oral)
75 mg (per each): $0.04 - $1.45
100 mg (per each): $0.05 - $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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet Extended Release 12 Hour, Oral, as hydrochloride:
Wellbutrin SR: 150 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake, polysorbate 80]
Zyban: 150 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c red #40(allura red ac)aluminum lake]
Generic: 100 mg, 150 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride:
Wellbutrin XL: 150 mg, 300 mg
Generic: 150 mg, 300 mg
Oral: May be taken without regard to meals. The manufacturer states that tablets should be swallowed whole; do not crush, chew, or divide. Chewing, crushing, injecting, or dividing long-acting products may increase seizure risk.
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.
Bariatric surgery: Bupropion has several ER formulations and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery. Providers should determine if the condition being treated can be safely monitored or if a switch to an alternative formulation is necessary (Ref). Bupropion is also available as an IR formulation.
Oral: May be taken without regard to meals. The manufacturer states do not crush, chew, or divide sustained- or extended-release tablets (hydrochloride and hydrobromide salt formulations); swallow whole. Chewing, crushing, injecting, or dividing long-acting products may increase seizure risk. 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.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Aplenzin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022108s022lbl.pdf#page=29
Forfivo XL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022497s008lbl.pdf#page=33
Wellbutrin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/018644s057lbl.pdf#page=32
Wellbutrin SR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020358s064lbl.pdf#page=34
Wellbutrin XL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021515s043lbl.pdf#page=29
Zyban: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020711s052lbl.pdf#page=38
Major depressive disorder (unipolar [excluding Zyban]): Treatment of unipolar 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.
Attention-deficit/hyperactivity disorder; Bipolar disorder, depressive episode; Methamphetamine use disorder; Sexual dysfunction associated with selective serotonin reuptake inhibitors
Bupropion is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of falls (O’Mahony 2023).
Aplenzin may be confused with Albenza, Relenza
BuPROPion may be confused with busPIRone
Forfivo XL may be confused with Forteo
Wellbutrin XL may be confused with Wellbutrin SR
Zyban may be confused with Diovan
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);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents With Seizure Threshold Lowering Potential: BuPROPion may increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
Ajmaline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Ajmaline. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of BuPROPion. Specifically, seizure threshold may be lowered. BuPROPion may increase adverse/toxic effects 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
Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): May increase adverse/toxic effects of BuPROPion. Risk C: Monitor
Antihepaciviral Combination Products: May decrease serum concentration of BuPROPion. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider Therapy Modification
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider Therapy Modification
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Benzhydrocodone. Risk C: Monitor
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brexanolone: BuPROPion may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual dose with bupropion; reduce to 25% of usual if used with both bupropion and a strong or moderate CYP3A4 inhibitor. These recommendations do not apply if treating major depressive disorder. Monitor for seizures. Risk D: Consider Therapy Modification
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Broom: CYP2D6 Inhibitors (Strong) may increase serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Carvedilol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Carvedilol. Risk C: Monitor
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Chlorpheniramine. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Citalopram: BuPROPion may increase adverse/toxic effects of Citalopram. BuPROPion may increase 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. Monitor for citalopram toxicities. Risk D: Consider Therapy Modification
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: CYP2D6 Inhibitors (Strong) may increase serum concentration of CloZAPine. Risk C: Monitor
Codeine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor
CYP2B6 Inducers (Moderate): May decrease serum concentration of BuPROPion. Risk C: Monitor
CYP2B6 Inducers (Weak): May decrease serum concentration of BuPROPion. Risk C: Monitor
CYP2B6 Inhibitors (Weak): May increase serum concentration of BuPROPion. Risk C: Monitor
Dapoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dapoxetine. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Dextromethorphan: CYP2D6 Inhibitors (Strong) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Digoxin: BuPROPion may decrease serum concentration of Digoxin. Risk C: Monitor
Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Direct Oral Anticoagulants (DOACs): BuPROPion may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
DULoxetine: CYP2D6 Inhibitors (Strong) may increase serum concentration of DULoxetine. Risk C: Monitor
Eliglustat: CYP2D6 Inhibitors (Strong) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Escitalopram: BuPROPion may increase adverse/toxic effects of Escitalopram. Risk C: Monitor
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider Therapy Modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: May decrease serum concentration of CYP2B6 Substrates (High risk with Inducers). Management: Avoid concomitant use of fexinidazole and CYP2B6 substrates when possible. If combined, monitor for reduced efficacy of the CYP2B6 substrate. Risk D: Consider Therapy Modification
Flecainide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Flecainide. Risk C: Monitor
FLUoxetine: May increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of FLUoxetine. Risk C: Monitor
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase serum concentration of FluPHENAZine. Risk C: Monitor
FluvoxaMINE: BuPROPion may increase adverse/toxic effects of FluvoxaMINE. Risk C: Monitor
Gefitinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Gefitinib. Risk C: Monitor
Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Haloperidol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Haloperidol. Risk C: Monitor
HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor
Iboga: CYP2D6 Inhibitors (Strong) may increase serum concentration of Iboga. Risk C: Monitor
Iloperidone: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. BuPROPion may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. BuPROPion may increase serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with bupropion. Monitor for increased iloperidone toxicities, including QTc prolongation and arrhythmias. Additionally, monitor for increased risk of seizures when these agents are combined. Risk D: Consider Therapy Modification
Indoramin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Indoramin. Risk C: Monitor
Iobenguane Radiopharmaceutical Products: BuPROPion may decrease therapeutic effects 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
Ioflupane I 123: Coadministration of BuPROPion and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects 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 antiseizure drugs. Risk D: Consider Therapy Modification
Lofexidine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Lofexidine. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumacaftor and Ivacaftor: May decrease serum concentration of CYP2B6 Substrates (High risk with Inducers). Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Maprotiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Maprotiline. Risk C: Monitor
Mequitazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mequitazine. Risk X: Avoid
Methadone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Methadone. Risk C: Monitor
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider Therapy Modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Metoprolol. Risk C: Monitor
Mexiletine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Mexiletine. Risk C: Monitor
MiFEPRIStone: May increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Monoamine Oxidase Inhibitors: May increase hypertensive effects of BuPROPion. Risk X: Avoid
Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Nebivolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Nebivolol. Risk C: Monitor
Nicergoline: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor
Nirmatrelvir and Ritonavir: May decrease serum concentration of BuPROPion. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Oliceridine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP2D6 Inhibitors (Strong) may increase serum concentration of Olmutinib. Risk C: Monitor
Opipramol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Opipramol. Risk C: Monitor
OxyCODONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of OxyCODONE. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
PARoxetine: BuPROPion may increase adverse/toxic effects of PARoxetine. Risk C: Monitor
Perhexiline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perhexiline. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Perphenazine. Risk C: Monitor
Pimozide: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pimozide. Risk X: Avoid
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pitolisant: CYP2D6 Inhibitors (Strong) may increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Primaquine: CYP2D6 Inhibitors (Strong) may decrease therapeutic effects of Primaquine. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Primaquine. Management: Consider alternatives to the combination of primaquine and strong CYP2D6 inhibitors. If concomitant use is necessary, monitor for signs and symptoms of possible primaquine treatment failure. Risk D: Consider Therapy Modification
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Propafenone: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propafenone. Risk C: Monitor
Propranolol: CYP2D6 Inhibitors (Strong) may increase serum concentration of Propranolol. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider Therapy Modification
Sertindole: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider Therapy Modification
Sertraline: BuPROPion may increase adverse/toxic effects of Sertraline. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sofpironium: CYP2D6 Inhibitors (Strong) may increase serum concentration of Sofpironium. Risk X: Avoid
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Taurursodiol: May increase serum concentration of CYP2B6 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider Therapy Modification
Thioridazine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Thioridazine. Risk X: Avoid
Thiotepa: May increase serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Ophthalmic). Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tolterodine: CYP2D6 Inhibitors (Strong) may increase serum concentration of Tolterodine. Risk C: Monitor
TraMADol: CYP2D6 Inhibitors (Strong) may increase serum concentration of TraMADol. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of TraMADol. Risk C: Monitor
Tricyclic Antidepressants: May increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Valbenazine: CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider Therapy Modification
Vilazodone: BuPROPion may increase adverse/toxic effects of Vilazodone. Risk C: Monitor
Vortioxetine: BuPROPion may increase adverse/toxic effects of Vortioxetine. BuPROPion may increase 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
Xanomeline: CYP2D6 Inhibitors (Strong) may increase serum concentration of Xanomeline. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: May increase adverse/toxic effects of BuPROPion. Specifically, the risk for seizures may be increased. BuPROPion may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023; WFSBP [Dodd 2018]). Preconception counseling is also recommended in patients treated for bipolar disorder (CANMAT/ISBD [Yatham 2018]). When treating depression, bupropion is not a first–line medication for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Agents other than bupropion are also preferred when first initiating treatment for bipolar disorder prior to conception (ACOG 2023). When medications are needed to treat bipolar disorder in patients planning to become pregnant, the lowest effective dose without underdosing is recommended (CANMAT/ISBD [Yatham 2018]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Bupropion and its metabolites cross the placenta (Fay 2021; Fokina 2016a).
Outcome data following maternal use of bupropion during pregnancy are available. An increased risk of overall congenital malformations has not been observed following maternal use of bupropion during pregnancy; however, studies specifically evaluating cardiovascular malformations often have inconsistent results due to differences in study design and confounders (Anderson 2020; BAP [McAllister-Williams 2017]; Hendrick 2017; Marks 2021; Turner 2019).
Pregnancy-induced physiologic changes do not alter the pharmacokinetic properties of bupropion and its metabolites in a clinically significant way (Fay 2021; Fokina 2016b).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight, preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, adverse neurodevelopment, and may increase the risk of postpartum psychosis. Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process (ACOG 2023).
Patients effectively treated for depression in the past may use that medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Agents other than bupropion may be preferred when treatment for depression or bipolar disorder is initiated for the first time during pregnancy (ACOG 2023; CANMAT/ISBD [Yatham 2018]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023). When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
When used as an aid for smoking cessation, available data do not support the use of bupropion in pregnant patients (Claire 2020; Kranzler 2021). Adverse pregnancy outcomes are associated with maternal cigarette smoking (refer to Nicotine monograph for details). All pregnant patients should be screened for nicotine use, regardless of form (cigarettes, e-cigarettes, hookahs, snus, vaping products, as well as lozenges, patches, and gum). Cessation of intake is recommended, and interventions should be individualized (ACOG 2020). The benefit of tobacco smoking cessation for pregnant patients is well documented; behavioral interventions are effective and recommended. Data related to pharmacotherapy interventions in pregnancy are limited and insufficient to make specific recommendations (USPSTF [Krist 2021]). When behavioral counseling is insufficient, the severity of maternal tobacco dependance should be considered along with the known risks of smoking and possible risks of the pharmacologic intervention (ACOG 2020; USPSTF [Krist 2021]).
When used for the treatment of attention-deficit/hyperactivity disorder (ADHD), data related to the use of medications during pregnancy are limited. If medications are needed to treat ADHD in a pregnant patient, agents other than bupropion may be preferred. However, patients already taking bupropion prior to pregnancy may continue therapy (BAP [McAllister-Williams 2017]; Ornoy 2021).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients ≤45 years of age with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Bupropion and its active metabolites are present in breast milk.
Multiple reports summarize data related to the presence of bupropion in breast milk.
• Breast milk was sampled from 4 patients 13 to 90 days postpartum. Lactating patients were taking bupropion sustained release 150 mg or 300 mg daily for at least 10 days prior to the study for smoking cessation. Sampling occurred prior to then 2 hours after the maternal dose. Peak bupropion breast milk concentrations ranged from 24.5 to 120 ng/mL (mean 64.1 ng/mL). Urine samples were obtained from 4 infants. Bupropion was present in the urine of 1 infant (41 ng/mL) at 34 days of age, born 5.5 weeks premature. Authors of the study calculated the relative infant dose (RID) of bupropion to be 2.2% to 10.6% of the weight–adjusted maternal dose (mean 5.7%). Metabolites were not evaluated in this study (Davis 2009).
• Data are available from 10 healthy lactating patients, average 12.5 months postpartum, who intended to stop breastfeeding. Bupropion 150 mg was administered once daily for 3 days, then increased to 300 mg for the treatment of smoking cessation. On day 7, one breast milk sample was obtained 1 to 12 hours after the dose (median 2.5 hours). Mean breast milk concentrations ranged from 4.2 to 168.3 ng/mL (bupropion), 9 to 242.1 ng/mL (hydroxybupropion), 25.4 to 142.9 ng/mL (erythrohydrobupropion), and 192.7 to 1,052.1 ng/mL (threohydrobupropion). The estimated infant dose via breast milk calculated by the authors of the study was 6.75 mcg/kg/day (bupropion), 15.75 mcg/kg/day (hydroxybupropion), 10.8 mcg/kg/day (erythrohydrobupropion), and 68.85 mcg/kg/day (threohydrobupropion), providing a RID of 2% (bupropion + metabolites) compared to the weight–adjusted maternal dose (Haas 2004).
• The presence of bupropion and metabolites in breast milk were described in a case report. The patient was taking bupropion 100 mg 3 times daily for depression and breastfeeding her 14 months of age child twice daily. Sampling occurred prior to and for 6 hours after the morning dose, 14 days after the start of treatment. The highest concentrations of bupropion (0.189 mcg/mL) and hydroxybupropion (0.132 mcg/mL) occurred 2 hours after the maternal dose. The highest concentration of threohydrobupropion (0.443 mcg/mL) occurred 1 hour after the dose. Bupropion was not detected in the infant plasma. Adverse events were not observed in the breastfeeding infant (Briggs 1993).
• 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 (Anderson 2021).
Seizures and sleep disturbances have been reported in infants following bupropion exposure via breast milk (Chaudron 2004; Hale 2010; Neuman 2014). Infants exposed to psychotropic medication via breast milk should be monitored for adverse effects (eg, over sedation, poor feeding) (BAP [McAllister-Williams 2017]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Patients effectively treated for depression during pregnancy may continue their medication postpartum unless contraindications to breastfeeding exist. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first time postpartum. When first initiating an antidepressant or treatment for bipolar disorder in a patient who is treatment naive and breastfeeding, an agent other than bupropion may be preferred (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]; CANMAT/ISBD [Yatham 2018]).
BP (baseline and periodically, especially when used in conjunction with nicotine transdermal replacement); body weight; suicidality (during the initial 1 to 2 months of therapy or during periods of dosage adjustments). Renal and hepatic function (baseline and as clinically indicated).
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).
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.
Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).
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)
Altered kidney function: 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.
Older adult: May be at risk of accumulation of bupropion and its metabolites.
Sex: AUC was approximately 13% higher in men.
