dextromethorphan/bupropion (Rx)

Brand and Other Names:Auvelity
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

dextromethorphan/bupropion

tablet, extended-release

  • 45mg/105mg

Major Depressive Disorders

Indicated for major depressive disorder (MDD)

1 tablet PO qDay in AM for 3 days, then increase to 1 tablet BID given at least 8 hr apart

Maximum recommended dose: 1 tablet BID; do not exceed 2 doses/24 hr

Dosage Modifications

Renal impairment

  • Mild (eGFR ≥60 mL/min/1.73 m2): No dose adjustment required
  • Moderate (eGFR 30-59 mL/min/1.73 m2): 1 tablet PO qAM (do not increase initial dose)
  • Severe (eGFR 15-29 mL/min/1.73 m2): Not recommended

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dose adjustment required
  • Severe (Child-Pugh C): Not recommended (not evaluated)

Poor CYP2D6 metabolizers or coadministration with CYP2D6 inhibitors

  • 1 tablet PO qAM (do not increase initial dose)

Switching to or from MOAI antidepressant

  • At least 14 days must elapse between discontinuing an MAOI and initiating dextromethorphan/bupropion
  • Conversely, at least 14 days must be allowed after stopping dextromethorphan/bupropion before starting an MAOI antidepressant

Dosing Considerations

Not for use during pregnancy; use alternate antidepressant for females planning to become pregnant

Screen patients for bipolar disorder, mania, or hypomania before initiating

Screen for other medications containing bupropion and dextromethorphan

Assess blood pressure, and monitor periodically during treatment

Safety and efficacy not established

Clinical trials did not include adults aged ≥65 years to determine if they respond differently from younger adults

Next:

Interactions

Interaction Checker

and dextromethorphan/bupropion

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      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (11)

            • eliglustat

              bupropion increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

            • isocarboxazid

              isocarboxazid and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

              isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.

            • phenelzine

              phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.

              phenelzine and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

            • pimozide

              bupropion will increase the level or effect of pimozide by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. Both bupropion and hydroxybupropion (major metabolite) are considered strong CYP2D6 inhibitors; additionally, bupropion and pimozide lower seizure threshold

            • procarbazine

              procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • rasagiline

              rasagiline and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

              rasagiline and dextromethorphan both increase serotonin levels. Contraindicated. Risk of psychosis episodes or bizarre behavior.

            • safinamide

              dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.

            • selegiline

              selegiline and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

            • selegiline

              selegiline and dextromethorphan both increase serotonin levels. Contraindicated.

            • selegiline transdermal

              selegiline transdermal and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

            • tranylcypromine

              tranylcypromine and bupropion both increase dopaminergic effects. Contraindicated. Bupropion inhibits reuptake of dopamine and norepinephrine (NE), and MAOIs decrease metabolism of dopamine and NE; coadministration increases risk for hypertensive reactions; allow at least 14 days between discontinuation of MAOI and initiating bupropion

              tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (52)

            • abametapir

              abametapir will increase the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP2B6 substrates. If not feasible, avoid use of abametapir.

            • amitriptyline

              amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • amoxapine

              amoxapine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • buspirone

              buspirone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • caffeine

              caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • chlorpromazine

              chlorpromazine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • citalopram

              citalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.

            • clomipramine

              clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              bupropion will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • clozapine

              clozapine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • desipramine

              desipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • cyclobenzaprine

              bupropion and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              doxepin and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

              duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

              duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

              escitalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Coadministration may decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6.

            • fluoxetine

              fluoxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              fluoxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • fluvoxamine

              fluvoxamine increases toxicity of bupropion by Other (see comment). Avoid or Use Alternate Drug. Comment: May lower seizure threshold; keep bupropion dose as low as possible.

              fluvoxamine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • grapefruit

              grapefruit will increase the level or effect of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • iobenguane I 131

              bupropion will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • imipramine

              imipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • levomilnacipran

              levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • linezolid

              bupropion, linezolid. serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

              linezolid and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lofepramine

              lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              bupropion and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              dextromethorphan and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • maprotiline

              maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • memantine

              memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • meperidine

              dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

              bupropion and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide intranasal

              bupropion will increase the level or effect of metoclopramide intranasal by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concurrent use of metoclopramide intranasal and strong CYP2D6 inhibitors is not recommended since the metoclopramide intranasal dose cannot be adjusted.

            • milnacipran

              milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • milnacipran

              milnacipran increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • nefazodone

              nefazodone increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

              nefazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • nortriptyline

              nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • olopatadine intranasal

              bupropion and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • ozanimod

              ozanimod increases toxicity of bupropion by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paroxetine

              paroxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              bupropion will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              paroxetine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

              paroxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • protriptyline

              protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • tedizolid

              tedizolid, bupropion. Either increases levels of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • selegiline transdermal

              selegiline transdermal and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • sertraline

              sertraline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • St John's Wort

              dextromethorphan and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • theophylline

              theophylline increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • thioridazine

              bupropion will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • trazodone

              trazodone increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

              trazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • trimipramine

              trimipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • venlafaxine

              venlafaxine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • venlafaxine

              venlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              venlafaxine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilazodone

              dextromethorphan, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              bupropion, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

            Monitor Closely (165)

            • 5-HTP

              5-HTP and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • almotriptan

              almotriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • amantadine

              amantadine, bupropion. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential CNS toxicity d/t synergistic central dopamine effect.

            • amifampridine

              bupropion increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amitriptyline

              amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amobarbital

              amobarbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • amoxapine

              amoxapine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amphetamine

              amphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

            • aripiprazole

              dextromethorphan, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              bupropion will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • atomoxetine

              bupropion will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • asenapine

              dextromethorphan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • benzhydrocodone/acetaminophen

              bupropion will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              benzhydrocodone/acetaminophen, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • betaxolol

              bupropion will increase the level or effect of betaxolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • brexpiprazole

              bupropion will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP2D6 inhibitors. If also administered with a strong/moderate CYP3A4 inhibitor, administer a quarter of brexpiprazole dose. NOTE: In MDD clinical trials, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine); thus, CYP considerations are already factored into general dosing recommendations and brexpiprazole may be administered without dosage adjustment in patients with MDD.

            • bupropion

              bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • butabarbital

              butabarbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • butalbital

              butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • cannabidiol

              cannabidiol, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.

            • carbamazepine

              carbamazepine will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • cariprazine

              dextromethorphan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • carvedilol

              bupropion will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP2B6 substrate, as needed, when coadministered with cenobamate.

            • chloroquine

              bupropion will increase the level or effect of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • chlorpromazine

              bupropion will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cinacalcet

              bupropion will increase the level or effect of cinacalcet by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • citalopram

              bupropion will increase the level or effect of citalopram by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • clobazam

              clobazam will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

            • clomipramine

              clomipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • clopidogrel

              clopidogrel will increase the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Plasma concentrations of bupropion may be significantly increased when coadministered with clopidogrel or other CYP2B6 inhibitors. The increase in plasma bupropion concentrations may cause an increase in adverse reactions including tremor, headache, insomnia, dry mouth, nausea, or seizures.

            • clozapine

              dextromethorphan, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • cocaine topical

              cocaine topical and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • codeine

              bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.

            • cyclosporine

              cyclosporine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • daridorexant

              bupropion and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • desipramine

              bupropion will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              desipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

              bupropion will increase the level or effect of deutetrabenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Strong CYP2D6 inhibitors increase the systemic exposure to the active dihydro-metabolites of deutetrabenazine by approximately 3-fold. Do not exceed 18 mg/dose and 36 mg/day of deutetrabenazine if coadministered with strong CYP2D6 inhibitors.

            • dexfenfluramine

              dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dextroamphetamine

              dextroamphetamine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              dextroamphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

            • dextroamphetamine transdermal

              dextroamphetamine transdermal, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .

              dextromethorphan, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

              bupropion will increase the level or effect of dextroamphetamine transdermal by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during dextroamphetamine initiation and after a dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and CYP2D6 inhibitor.

            • dextromethorphan

              bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • dihydroergotamine

              dextromethorphan and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • diazepam intranasal

              diazepam intranasal, bupropion. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • difelikefalin

              difelikefalin and bupropion both increase sedation. Use Caution/Monitor.

            • digoxin

              bupropion will decrease the level or effect of digoxin by Other (see comment). Use Caution/Monitor. Monitor for decreased digoxin concentrations; bupropion may induce OATP4C1 transporter, which is involved in digoxin renal elimination

            • dihydroergotamine intranasal

              dextromethorphan and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • doxepin

              bupropion will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              doxepin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • duloxetine

              bupropion will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Coadministration with hepatic inducers reduced bupropion AUC and Cmax; hydroxybupropion (active metabolite) Cmax was increased

            • eletriptan

              eletriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eluxadoline

              bupropion increases levels of eluxadoline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2D6 inhibitors.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of bupropion by unknown mechanism. Use Caution/Monitor.

            • ergotamine

              dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • fenfluramine

              fenfluramine, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

              fenfluramine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

              dextromethorphan and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • fesoterodine

              bupropion will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • fluphenazine

              dextromethorphan, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • flecainide

              bupropion will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Coadministration of bupropion and flecainide should be approached with caution and should be initiated at the lower end of the dose range of flecainide. If bupropion is added to the treatment regimen of a patient already receiving flecainide, consider decreasing the dose of flecainide.

            • fluoxetine

              bupropion will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • fluphenazine

              bupropion will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine will increase the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • frovatriptan

              frovatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • gabapentin

              gabapentin, bupropion. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, bupropion. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • galantamine

              bupropion will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ganaxolone

              bupropion and ganaxolone both increase sedation. Use Caution/Monitor.

            • haloperidol

              bupropion will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              dextromethorphan, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • hydrocodone

              bupropion will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • iloperidone

              dextromethorphan, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • hydromorphone

              bupropion will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • iloperidone

              bupropion will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • imipramine

              bupropion will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              imipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • ioflupane I 123

              bupropion decreases effects of ioflupane I 123 by receptor binding competition. Use Caution/Monitor. Drugs that bind to dopamine transporter receptor with high affinity may interfere with the image following ioflupane I 123 administration.

            • isoniazid

              dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

            • L-tryptophan

              dextromethorphan and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lasmiditan

              lasmiditan, bupropion. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.

              lemborexant, bupropion. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • letermovir

              letermovir increases levels of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levodopa

              bupropion increases effects of levodopa by pharmacodynamic synergism. Use Caution/Monitor. There is a higher incidence of adverse reactions with concurrent use of bupropion with levodopa. Use small initial dosages and small, gradual dosage increases of bupropion.

            • lisdexamfetamine

              lisdexamfetamine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • lithium

              dextromethorphan and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lofepramine

              bupropion will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              lofepramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • lofexidine

              bupropion will increase the level or effect of lofexidine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Concomitant use of lofexidine with strong CYP2D6 inhibitors may increase lofexidine plasma levels. Monitor for symptoms of orthostasis and bradycardia if coadministered with a CYP2D6 inhibitor. Consider lofexidine dose reduction.

            • loratadine

              bupropion will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • loxapine

              dextromethorphan, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • loxapine inhaled

              dextromethorphan, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • lsd

              dextromethorphan and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .

            • lumefantrine

              lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lurasidone

              dextromethorphan, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              lurasidone, bupropion. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              maprotiline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of maprotiline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

              dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • metformin

              bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.

            • methamphetamine

              bupropion will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              methamphetamine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • methylenedioxymethamphetamine

              methylenedioxymethamphetamine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • metoprolol

              bupropion will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mexiletine

              bupropion will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mifepristone

              mifepristone will increase the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • mipomersen

              mipomersen, bupropion. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirtazapine

              bupropion will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • molindone

              dextromethorphan, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • morphine

              dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

              bupropion will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • naratriptan

              naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nebivolol

              bupropion will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • nelfinavir

              nelfinavir, bupropion. decreasing metabolism. Use Caution/Monitor. Incr levels of bupropion, but decr levels of active metabolites. .

            • nilotinib

              nilotinib, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • nirmatrelvir

              nirmatrelvir will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Buproion extensively metabolized by CYP2B6 to active metabolite. Monitor for adequate clinical response to bupropion when coadministered with CYP2B6 inhibitors.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Bupropion is extensively metabolized by CYP2B6 to active metabolite. Monitor for adequate clinical response to bupropion when coadministered with CYP2B6 inhibitors.

            • nortriptyline

              bupropion will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              nortriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • olanzapine

              dextromethorphan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • oliceridine

              bupropion will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

              bupropion, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • oxycodone

              bupropion will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • paliperidone

              dextromethorphan, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • panobinostat

              panobinostat will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

            • pazopanib

              pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, dextromethorphan. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • perphenazine

              dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • phenobarbital

              phenobarbital will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Decrease levels of bupropion.

            • pimavanserin

              dextromethorphan, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pimozide

              dextromethorphan, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • pitolisant

              bupropion will increase the level or effect of pitolisant by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If coadministered with strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg/day and increase after 7 days to maximum of 17.8 mg/day. For patients currently taking pitolisant, reduce pitolisant dose by half upon initiating strong CYP2D6 inhibitors.

            • pivmecillinam

              pivmecillinam increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • pregabalin

              pregabalin, bupropion. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • prochlorperazine

              bupropion will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              prochlorperazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • promethazine

              bupropion will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propafenone

              bupropion will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propranolol

              bupropion will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • protriptyline

              protriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • quetiapine

              dextromethorphan, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • quinidine

              quinidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • remimazolam

              remimazolam, bupropion. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • rifampin

              rifampin will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

            • risperidone

              dextromethorphan, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              bupropion will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ritonavir

              ritonavir decreases levels of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Ritonavir decreases levels of bupropion by inducing CYP2B6. Bupropion levels decreased by 20-80%, increased doses of bupropion may be required .

            • rizatriptan

              rizatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rolapitant

              rolapitant will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor for adverse reactions when unable to avoid coadministration with narrow therapeutic index CYP2D6 substrates.

            • SAMe

              dextromethorphan and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • secobarbital

              secobarbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .

            • sertraline

              sertraline increases levels of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sertraline may inhibit hydroxylation of bupropion to its major active metabolite hydroxybupropion.

              bupropion will increase the level or effect of sertraline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • solriamfetol

              bupropion and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • sorafenib

              sorafenib, bupropion. decreasing metabolism. Use Caution/Monitor. Incr levels of bupropion, but decr levels of active metabolites. .

            • stiripentol

              stiripentol, bupropion. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.

            • sufentanil SL

              sufentanil SL, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sumatriptan

              sumatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tamoxifen

              bupropion decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

              bupropion will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Inhibition of CYP2D6 decreases metabolism of tamoxifen to active metabolite, endoxifen

            • tamsulosin

              bupropion increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tapentadol

              bupropion and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Consider increasing dosage of interacting drug, if necessary

            • temocillin

              temocillin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • thiothixene

              dextromethorphan, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • ticarcillin

              ticarcillin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • timolol

              bupropion will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tolterodine

              bupropion will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tramadol

              bupropion will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • trifluoperazine

              dextromethorphan, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              bupropion will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • trimipramine

              trimipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • ziprasidone

              dextromethorphan, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • valbenazine

              bupropion will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Consider reducing valbenazine dose based on tolerability if coadministered with a strong CYP2D6 inhibitor.

            • venlafaxine

              bupropion will increase the level or effect of venlafaxine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • zolmitriptan

              zolmitriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (40)

            • amiodarone

              amiodarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • armodafinil

              armodafinil, bupropion. increasing metabolism. Minor/Significance Unknown. Decr levels of bupropion, but incr levels of active metabolites. .

            • asenapine

              asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • carbamazepine

              carbamazepine decreases levels of bupropion by increasing metabolism. Minor/Significance Unknown.

            • cefamandole

              cefamandole increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • cefpirome

              cefpirome increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • celecoxib

              celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • chloroquine

              chloroquine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • darifenacin

              darifenacin will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dexfenfluramine

              bupropion will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • diphenhydramine

              diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • donepezil

              bupropion will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dronedarone

              dronedarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • encainide

              bupropion will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ethanol

              ethanol, bupropion. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

            • fluphenazine

              fluphenazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • haloperidol

              haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • imatinib

              imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • maraviroc

              maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • meperidine

              meperidine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • modafinil

              modafinil, bupropion. increasing metabolism. Minor/Significance Unknown. Decr levels of bupropion, but incr levels of active metabolites. .

            • nicotine inhaled

              bupropion, nicotine inhaled. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypertension.

            • nicotine intranasal

              bupropion, nicotine intranasal. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypertension.

            • nilotinib

              nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perhexiline

              bupropion will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • promazine

              bupropion will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              promazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • promethazine

              promethazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • propafenone

              propafenone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • quinacrine

              quinacrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ritonavir

              ritonavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • sertraline

              sertraline will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • thioridazine

              thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              thioridazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • tipranavir

              tipranavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • trifluoperazine

              trifluoperazine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.

            • tropisetron

              bupropion will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10%

            Dizziness (16%)

            Nausea (13%)

            1-10%

            Headache (8%)

            Diarrhea (7%)

            Somnolence (7%)

            Dry mouth (6%)

            Sexual dysfunction (6%)

            Hyperhidrosis (5%)

            Anxiety (4%)

            Constipation (4%)

            Decreased appetite (4%)

            Insomnia (4%)

            Arthralgia (3%)

            Fatigue (3%)

            Paresthesia (3%)

            Vision blurred (3%)

            Postmarketing Reports

            Dextromethorphan

            • Drowsiness, dizziness, nervousness or restlessness, nausea, vomiting, and stomach pain

            Bupropion

            • Body: Arthralgia, myalgia, and fever with rash and other symptoms suggestive of delayed hypersensitivity
            • Cardiovascular: Complete atrioventricular block, extrasystoles, hypotension, hypertension (in some cases severe), phlebitis, and pulmonary embolism
            • Digestive: Colitis, esophagitis, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, intestinal perforation, pancreatitis, and stomach ulcer
            • Endocrine: Hyperglycemia, hypoglycemia, hyponatremia, and syndrome of inappropriate antidiuretic hormone secretion
            • Hemic and Lymphatic: Anemia, leukocytosis, leukopenia, lymphadenopathy, pancytopenia, and thrombocytopenia
            • Metabolic and nutritional: Glycosuria
            • Musculoskeletal: Muscle rigidity/fever/rhabdomyolysis and muscle weakness
            • Nervous system: Abnormal electroencephalogram (EEG), aggression, agitation, akinesia, aphasia, coma, completed suicide, delirium, delusions, depression, dysarthria, euphoria, extrapyramidal syndrome (dyskinesia, dystonia, hypokinesia, parkinsonism), hallucinations, homicidal ideation, hostility, increased libido, manic reaction, neuralgia, neuropathy, panic, paranoid ideation, psychosis, restlessness, suicide ideation, suicide attempt, and unmasking tardive dyskinesia
            • Respiratory: Pneumonia
            • Skin: Alopecia, angioedema, exfoliative dermatitis, hirsutism, and Stevens-Johnson syndrome
            • Special senses: Deafness, increased intraocular pressure, and mydriasis
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            Warnings

            Black Box Warnings

            Antidepressants increased risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies

            Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors

            Not approved for use in pediatric patients

            Contraindications

            Seizure disorders

            Current or prior diagnosis of bulimia or anorexia nervosa (higher incidence of seizures with immediate-release bupropion)

            Abrupt discontinuance of alcohol, benzodiazepine, barbiturates, or antiepileptic drugs

            Taking, or within 14 days of stopping, MAOIs; starting dextromethorphan/bupropion in patients treated with reversible MAOIs (eg, linezolid, IV methylene blue)

            Known hypersensitivity to bupropion, dextromethorphan, or other components

            Cautions

            Serotonin syndrome reported; if concomitant use of this medication with other serotonergic drugs clinically warranted, inform patients of increased risk for serotonin syndrome and monitor for symptoms; discontinue treatment and/or concomitant serotonergic drug immediately if above symptoms occur, and initiate supportive symptomatic treatment

            Bupropion may elevated blood pressure; risk of hypertension increased if coadministered with MAOIs or other drugs that increase dopaminergic or noradrenergic activity

            Caution with angle-closure glaucoma; pupillary dilation that occurs following use of many antidepressant drugs, including bupropion, may trigger an angle-closure attack in patients with anatomically narrow angles who do not have a patent iridectomy

            May cause dizziness; take precautions to reduce falls and caution patients regarding operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy does not affect them adversely

            May cause fetal harm; use alternate treatment for females planning to become pregnant

            Suicidality

            • In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (aged <24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients aged >24 years
            • Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, as well as at times of dosage changes
            • Counsel family members or caregivers of patients to monitor for changes in behavior and to alert healthcare provider; consider changing therapeutic regimen, including possibly discontinuing therapy, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors

            Psychosis/neuropsychiatric reactions

            • Bupropion: Depressed patients treated with bupropion have had a variety of neuropsychiatric signs and symptoms, including delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion; symptoms may abate with dose reduction and/or treatment withdrawal
            • Dextromethorphan: Overdose can cause toxic psychosis, stupor, coma, and hyperexcitability
            • Antidepressants can precipitate manic, mixed, or hypomanic manic episode; risk increased in patients who have bipolar disorder or have risk factors for bipolar disorder
            • Screen patients for bipolar disorder and use of other bupropion- or dextromethorphan-containing products before initiating

            Seizures

            • Bupropion can cause seizure; risk of seizure with bupropion is dose-related; use contraindicated in patients with seizures
            • If concomitant use of this medication with other bupropion-containing products is clinically warranted, inform patients of the risk; discontinue therapy, and do not restart treatment if the patient experiences a seizure

            Drug interaction overview

            • Bupropion (and metabolites): CYP2D6 inhibitor; CYP2B6 substrate
            • Dextromethorphan: CYP2D6 substrate (major)
            • MAOIs
              • Contraindicated
              • Coadministration (or within 14 days) increases risk of hypertensive crisis and serotonin syndrome
            • Serotonin syndrome
              • Monitor for symptoms of serotonin syndrome
              • Coadministration with other serotonergic drugs (eg, SSRIs, TCAs) increases risk of serotonin syndrome, a potentially life-threatening condition with changes that include altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor
            • Drugs that lower seizure threshold
              • Caution
              • Bupropion can cause seizure; coadministration with other drugs that lower seizure threshold may increase risk
              • If seizure occurs, discontinue dextromethorphan/bupropion and do not restart
            • Strong CYP2D6 inhibitor
              • Modify (decrease) dextromethorphan/bupropion dose
              • Strong CYP2D6 inhibitors increase dextromethorphan plasma concentrations, which may result in somnolence and dizziness
            • Strong CYP2B5 inducers
              • Avoid
              • Strong CYP2B6 inducers decrease plasma concentrations of bupropion
            • CYP2D6 substrates
              • May need to modify dose of CYP2D6 substrate
              • Bupropion may increase systemic exposure of CYP2D6 substrates; dose modification of CYP2D6 substrates with narrow therapeutic indexes may be necessary
              • Conversely, drugs requiring metabolic activation by CYP2D6 may have reduced efficacy and require an increased dose
            • Digoxin
              • Monitor digoxin levels
              • Coadministration may decrease plasma digoxin levels
              • Digoxin exposure was decreased when a single oral dose of 0.5-mg digoxin was administered 24 hr after a single oral dose of extended-release 150 mg bupropion in healthy volunteers
            • Dopaminergic drugs
              • Caution
              • Coadministration of levodopa or amantadine with bupropion may cause CNS toxicity, including restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, and dizziness
            • Alcohol
              • Avoid alcohol during treatment
              • Bupropion can increase adverse neuropsychiatric events or reduce alcohol tolerance
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            Pregnancy & Lactation

            Pregnancy

            Not recommended during pregnancy

            Based on animal studies, may cause fetal harm when administered during pregnancy

            Encourage patients to register for the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or online at womensmentalhealth.org/research/pregnancyregistry/antidepressants/

            Clinical considerations

            • A prospective, longitudinal study followed 201 pregnant women with history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy
            • Women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than women who continued antidepressants
            • Consider maternal risks of untreated depression and potential effects on fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum

            Lactation

            Owing to potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment and for 5 days after final dose

            Dextromethorphan

            • Neurotoxicity observed in juvenile rats treated with dextromethorphan/quinidine on postnatal day 7, which corresponds to third trimester of gestation through the first few months of life and may extend through the first 3 years of human life
            • Unknown if dextromethorphan is present in human milk; data are not available regarding effects on breastfed infant or on milk production

            Bupropion

            • There are no data on the effects of bupropion or its metabolites on milk production
            • Data from postmarketing reports are limited; use in lactating patients has not identified a clear association of adverse reactions in the breastfed infant

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Dextromethorphan: Uncompetitive N-methyl-D-aspartate receptor (NMDA) receptor antagonist (glutamate receptor modulator) with multimodal activity; also is an agonist of sigma-1 receptor

            Bupropion: Serves to increase bioavailability of dextromethorphan; also inhibits norepinephrine and dopamine reuptake

            Absorption

            Peak plasma time: 3 hr (dextromethorphan); 2 hr (bupropion)

            Steady state achieved within 8 days

            Distribution

            Protein bound

            • Dextromethorphan: 60-70%
            • Bupropion and hydroxybupropion metabolite: 84%
            • Threohydroxybupropion metabolite: ~42%

            Metabolism

            Dextromethorphan primarily metabolized by CYP2D6 to dextrorphan

            Bupropion extensively metabolized to 3 active metabolites via hydroxylation

            CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion

            Elimination

            Half-life

            • CYP2D6 extensive metabolizers: Dextromethorphan increased ~3-fold to 22 hr, compared with dextromethorphan given without bupropion
            • Bupropion: 15 hr
            • Bupropion active metabolites: Hydroxybupropion, erythrohydroxybupropion, and threohydroxybupropion were ~35, 44 and 33 hr, respectively

            Excretion

            Dextromethorphan

            • CYP2D6 extensive metabolizers: 37-52% recovered in urine (<2% unchanged)
            • CYP2D6 poor metabolizers: 45-83% recovered in urine (~26% unchanged)
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            Administration

            Oral Administration

            May administer with or without food

            Swallow tablets whole; do not crush, divide, or chew

            Storage

            Store in original bottle at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)

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            Patient Handout

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.