dextromethorphan (OTC)

Cough

Liquid and syrup: 10-20 mg PO q4hr OR 30 mg q6-8hr

Gel: 30 mg PO q6-8hr; not to exceed 120 mg/24hr

Extended release: 60 mg PO q12hr; not to exceed 120 mg/24hr

Lozenges: 5-15 mg PO q1-4hr; not to exceed 120 mg/day

Strips: 30 mg PO q6-8hr; not to exceed 120 mg/day

Dosing considerations

• Abuse potential much lower than codeine
• About 15-30 mg dextromethorphan equal to 8-15 mg codeine as an antitussive

Cough

<4 years

• Prescription only

Extended release

• 4-6 years: 15 mg PO twice daily; not to exceed 30 mg/24hr
• 6-12 years: 30 mg PO twice daily; not to exceed 60 mg/24hr
• >12 years: 60 mg PO q12hr; not to exceed 120 mg/24hr

Liquid/Syrup

• 4-6 years: 7.5 mg q6-8hr (not to exceed 30 mg/day)
• 6-12 years: 15 mg PO q6-8hr; not to exceed 60 mg/24hr
• 12 years: 10-20 mg PO q4hr or 30 mg q6-8hr not to exceed 120 mg/24hr

Gel

• >12 years: 30 mg PO q6-8hr; not to exceed 120 mg/24hr

Lozenges

• 6-12 years: 5-10 mg q1-4hr; not to exceed 60 mg/day
• >12 years: 5-15 mg PO q1-4hr; not to exceed 120 mg/day

Strips

• 6-12 years: 15 mg PO q6-8hr; not to exceed 60 mg/day
• >12 years: 30 mg PO q6-8hr; not to exceed 120 mg/day

Dosing considerations

• Potential toxic dose <6 years: 10 mg/kg  
• About 15-30 mg dextromethorphan equal to 8-15 mg codeine as an antitussive

Contraindicated (7)

• isocarboxazid

  isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.

• phenelzine

  phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.

• procarbazine

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

• rasagiline

  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 dextromethorphan both increase serotonin levels. Contraindicated.

• tranylcypromine

  tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.

Serious - Use Alternative (34)

• 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.

• 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.

• desipramine

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

• escitalopram

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

• 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.

• fluvoxamine

  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.

• 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

  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

  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.

• milnacipran

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

• nefazodone

  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.

• paroxetine

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

• 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.

• trazodone

  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 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. .

Monitor Closely (59)

• 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.

• 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).

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of dextromethorphan 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).

• bupropion

  bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 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).

• 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.

• 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

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

• 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

• dexfenfluramine

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

• dextroamphetamine

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

• dextroamphetamine transdermal

  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).

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• eletriptan

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

• ergotamine

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

• fenfluramine

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

• 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).

• frovatriptan

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

• haloperidol

  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).

• 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).

• 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.

• letermovir

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

• lithium

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

• 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.

• 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).

• mirtazapine

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

• 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.

• naratriptan

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

• 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).

• 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.

• 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).

• 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).

• 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.

• 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).

• 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.

• 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.

• 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).

• tramadol

  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).

• 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).

• zolmitriptan

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

Minor (22)

• amiodarone

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

• asenapine

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

• 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.

• diphenhydramine

  diphenhydramine will increase the level or effect of dextromethorphan 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.

• 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.

• 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.

• perphenazine

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

• 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.

• tipranavir

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

• 5-HTP

  Monitor Closely (1)5-HTP and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• abiraterone

  Monitor Closely (1)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

  Monitor Closely (1)almotriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• amiodarone

  Minor (1)amiodarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• amitriptyline

  Serious - Use Alternative (1)amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• amoxapine

  Serious - Use Alternative (1)amoxapine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• aripiprazole

  Monitor Closely (1)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).

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• asenapine

  Monitor Closely (1)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).Minor (1)asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• bupropion

  Monitor Closely (1)bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• buspirone

  Serious - Use Alternative (1)buspirone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• cariprazine

  Monitor Closely (1)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).

• celecoxib

  Minor (1)celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chloroquine

  Minor (1)chloroquine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cimetidine

  Minor (1)cimetidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• citalopram

  Serious - Use Alternative (1)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.

• clobazam

  Monitor Closely (1)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

  Serious - Use Alternative (1)clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• clozapine

  Monitor Closely (1)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

  Monitor Closely (1)cocaine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• darifenacin

  Minor (1)darifenacin will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• desipramine

  Serious - Use Alternative (1)desipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• desvenlafaxine

  Monitor Closely (1)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 mgSerious - Use Alternative (1)dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• dexfenfluramine

  Monitor Closely (1)dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• dextroamphetamine

  Monitor Closely (1)dextroamphetamine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• dextroamphetamine transdermal

  Monitor Closely (1)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).

• dihydroergotamine

  Monitor Closely (1)dextromethorphan and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dihydroergotamine intranasal

  Monitor Closely (1)dextromethorphan and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

• diphenhydramine

  Minor (1)diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• doxepin

  Serious - Use Alternative (1)doxepin and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• dronedarone

  Minor (1)dronedarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• duloxetine

  Serious - Use Alternative (2)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.

• eletriptan

  Monitor Closely (1)eletriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• ergotamine

  Monitor Closely (1)dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• escitalopram

  Serious - Use Alternative (1)escitalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• fenfluramine

  Monitor Closely (2)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.

• fluoxetine

  Serious - Use Alternative (2)fluoxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (1)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).

• fluvoxamine

  Serious - Use Alternative (1)fluvoxamine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• frovatriptan

  Monitor Closely (1)frovatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• grapefruit

  Serious - Use Alternative (1)grapefruit will increase the level or effect of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• haloperidol

  Monitor Closely (1)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).Minor (1)haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• iloperidone

  Monitor Closely (1)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).

• imatinib

  Minor (1)imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imipramine

  Serious - Use Alternative (1)imipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• isocarboxazid

  Contraindicated (1)isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.

• isoniazid

  Monitor Closely (1)dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

• L-tryptophan

  Monitor Closely (1)dextromethorphan and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

• letermovir

  Monitor Closely (1)letermovir increases levels of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levomilnacipran

  Serious - Use Alternative (1)levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• linezolid

  Serious - Use Alternative (1)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.

• lithium

  Monitor Closely (1)dextromethorphan and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

• lofepramine

  Serious - Use Alternative (1)lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• lorcaserin

  Serious - Use Alternative (1)dextromethorphan and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• loxapine

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)dextromethorphan and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

• lumefantrine

  Monitor Closely (1)lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)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).

• maprotiline

  Serious - Use Alternative (1)maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• maraviroc

  Minor (1)maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Minor (1)marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• memantine

  Serious - Use Alternative (1)memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

• meperidine

  Serious - Use Alternative (1)dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• methylene blue

  Serious - Use Alternative (1)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.

• milnacipran

  Serious - Use Alternative (1)milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• mirtazapine

  Monitor Closely (1)dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

• molindone

  Monitor 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).

• morphine

  Monitor Closely (1)dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

• naratriptan

  Monitor Closely (1)naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• nefazodone

  Serious - Use Alternative (1)nefazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• nilotinib

  Minor (1)nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• nortriptyline

  Serious - Use Alternative (1)nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• olanzapine

  Monitor 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).

• paliperidone

  Monitor 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).

• panobinostat

  Monitor 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.

• parecoxib

  Minor (1)parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• paroxetine

  Serious - Use Alternative (2)paroxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
  
  paroxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• pazopanib

  Monitor Closely (1)pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor 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.

• pentazocine

  Monitor Closely (1)dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

• perphenazine

  Monitor Closely (1)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).Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phenelzine

  Contraindicated (1)phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.

• pimavanserin

  Monitor 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).

• pimozide

  Monitor 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).

• procarbazine

  Contraindicated (1)procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

• propafenone

  Minor (1)propafenone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• protriptyline

  Serious - Use Alternative (1)protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• quetiapine

  Monitor Closely (1)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).

• quinacrine

  Minor (1)quinacrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• quinidine

  Monitor Closely (1)quinidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• ranolazine

  Minor (1)ranolazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rasagiline

  Contraindicated (1)rasagiline and dextromethorphan both increase serotonin levels. Contraindicated. Risk of psychosis episodes or bizarre behavior.

• risperidone

  Monitor Closely (1)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).

• ritonavir

  Minor (1)ritonavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rizatriptan

  Monitor Closely (1)rizatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• rolapitant

  Monitor Closely (1)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.

• safinamide

  Contraindicated (1)dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.

• SAMe

  Monitor Closely (1)dextromethorphan and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

• selegiline

  Contraindicated (1)selegiline and dextromethorphan both increase serotonin levels. Contraindicated.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• sertraline

  Serious - Use Alternative (1)sertraline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)sertraline will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• St John's Wort

  Serious - Use Alternative (1)dextromethorphan and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• sumatriptan

  Monitor Closely (1)sumatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• sumatriptan intranasal

  Monitor Closely (1)sumatriptan intranasal and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.

• thioridazine

  Minor (1)thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (1)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).

• tipranavir

  Minor (1)tipranavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tramadol

  Monitor Closely (1)dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• tranylcypromine

  Contraindicated (1)tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.

• trazodone

  Serious - Use Alternative (1)trazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• trifluoperazine

  Monitor Closely (1)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).

• trimipramine

  Serious - Use Alternative (1)trimipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• venlafaxine

  Serious - Use Alternative (2)venlafaxine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
  
  venlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• vilazodone

  Serious - Use Alternative (1)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. .

• ziprasidone

  Monitor Closely (1)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).

• zolmitriptan

  Monitor Closely (1)zolmitriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.