Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (166)
- 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. .
- sparsentan
sparsentan will decrease the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.
- 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.
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
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
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.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)
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)
Images
Formulary
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