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).maprotilineMonitor Closely (2)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.Serious - Use Alternative (1)maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.maravirocMinor (1)maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.marijuanaMinor (1)marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.memantineSerious - Use Alternative (1)memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.meperidineMinor (1)meperidine increases toxicity of bupropion by unspecified interaction mechanism. Minor/Significance Unknown. May lower seizure threshold; keep bupropion dose as low as possible.Serious - Use Alternative (1)dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.metforminMonitor Closely (1)bupropion increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Bupropion may inhibit OCT2 mediated renal excretion of metformin.methamphetamineMonitor Closely (2)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.methylene blueSerious - Use Alternative (2)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.methylenedioxymethamphetamineMonitor Closely (1)methylenedioxymethamphetamine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.metoclopramide intranasalSerious - Use Alternative (1)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.metoprololMonitor Closely (1)bupropion will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.mexiletineMonitor Closely (1)bupropion will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.mifepristoneMonitor Closely (1)mifepristone will increase the level or effect of bupropion by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.milnacipranSerious - Use Alternative (2)milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. 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.mipomersenMonitor Closely (1)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.mirtazapineMonitor Closely (2)dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. bupropion will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.modafinilMinor (1)modafinil, bupropion. increasing metabolism. Minor/Significance Unknown. Decr levels of bupropion, but incr levels of active metabolites. .molindoneMonitor Closely (1)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).morphineMonitor Closely (2)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.naratriptanMonitor Closely (1)naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.nebivololMonitor Closely (1)bupropion will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.nefazodoneSerious - Use Alternative (2)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.nelfinavirMonitor Closely (1)nelfinavir, bupropion. decreasing metabolism. Use Caution/Monitor. Incr levels of bupropion, but decr levels of active metabolites. .nicotine inhaledMinor (1)bupropion, nicotine inhaled. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypertension.nicotine intranasalMinor (1)bupropion, nicotine intranasal. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypertension.nilotinibMonitor Closely (1)nilotinib, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .Minor (1)nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.nirmatrelvirMonitor Closely (1)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/ritonavirMonitor Closely (1)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.nortriptylineMonitor Closely (2)nortriptyline 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 nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.olanzapineMonitor Closely (1)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).oliceridineMonitor Closely (2)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.olopatadine intranasalSerious - Use Alternative (1)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. oxycodoneMonitor Closely (1)bupropion will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.ozanimodSerious - Use Alternative (1)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.paliperidoneMonitor Closely (1)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).panobinostatMonitor Closely (1)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.parecoxibMinor (1)parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.paroxetineSerious - Use Alternative (4)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.pazopanibMonitor Closely (1)pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.peginterferon alfa 2bMonitor Closely (1)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.pentazocineMonitor Closely (1)dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.pentobarbitalMonitor Closely (1)pentobarbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .perhexilineMinor (1)bupropion will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.perphenazineMonitor Closely (3)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.Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.phenelzineContraindicated (2)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 bupropionphenobarbitalMonitor Closely (1)phenobarbital will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Decrease levels of bupropion.pimavanserinMonitor Closely (1)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).pimozideContraindicated (1)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 thresholdMonitor Closely (1)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).pitolisantMonitor Closely (1)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.pivmecillinamMonitor Closely (1)pivmecillinam increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.pregabalinMonitor Closely (1)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.primidoneMonitor Closely (1)primidone, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .procarbazineContraindicated (1)procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.prochlorperazineMonitor Closely (2)prochlorperazine increases toxicity of bupropion by unspecified interaction