acetaminophen/doxylamine/dextromethorphan (OTC)

Cough, Sore Throat, Rhinorrhea, Fever, Headache, Minor Aches & Pains

1-2 Tablespoons (15-30mL) PO q6hr; not to exceed a cumulative dose of acetaminophen 4 g/day and dextromethorphan 120 mg/day

2 capsules PO q6hr; not to exeed 8 capsules/day

Liquid formulation ingredients vary in dosage; follow specific brand instructions

Cough, Sore Throat, Rhinorrhea, Fever, Headache, Minor Aches & Pains

<12 Years Old

• Ask a pediatrician

>12 Years Old

• 2 Tablespoons (30mL) PO q6hr; not to exceed 120 mL/day
• 2 capsules PO q6hr; not to exeed 8 capsules/day

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 (44)

• 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.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• buspirone

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

• calcium/magnesium/potassium/sodium oxybates

  doxylamine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• 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.

• fentanyl

  fentanyl, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  fentanyl intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  fentanyl transdermal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  fentanyl transmucosal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• 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.

• hydrocodone

  hydrocodone, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• imipramine

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

• isocarboxazid

  isocarboxazid increases effects of doxylamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• lemborexant

  lemborexant, doxylamine. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

• 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.

• lonafarnib

  acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• 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 doxylamine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
  
  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.

• metoclopramide intranasal

  doxylamine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• 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.

• olopatadine intranasal

  doxylamine 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.

• 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.

• pexidartinib

  acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• pretomanid

  acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• 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.

• selinexor

  selinexor, doxylamine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

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

Monitor Closely (234)

• 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.

• alfentanil

  doxylamine and alfentanil both increase sedation. Use Caution/Monitor.

• almotriptan

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

• alprazolam

  alprazolam and doxylamine both increase sedation. Use Caution/Monitor.

• amifampridine

  doxylamine 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

  doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  amobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• amoxapine

  doxylamine and amoxapine both increase sedation. 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. .

• apalutamide

  apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• apomorphine

  doxylamine and apomorphine both increase sedation. Use Caution/Monitor.

• 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).
  
  doxylamine and aripiprazole both increase sedation. Use Caution/Monitor.

• artemether/lumefantrine

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

• atogepant

  acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 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).

• avapritinib

  acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axitinib

  acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  azelastine and doxylamine both increase sedation. Use Caution/Monitor.

• baclofen

  doxylamine and baclofen both increase sedation. Use Caution/Monitor.

• belladonna and opium

  doxylamine and belladonna and opium both increase sedation. Use Caution/Monitor.

• benperidol

  doxylamine and benperidol both increase sedation. Use Caution/Monitor.

• benzphetamine

  doxylamine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• brexanolone

  brexanolone, doxylamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brompheniramine

  brompheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• bupivacaine implant

  acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

  doxylamine and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  doxylamine and buprenorphine buccal both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  doxylamine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• bupropion

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

• busulfan

  acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• butabarbital

  butabarbital and doxylamine both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital and doxylamine both increase sedation. Use Caution/Monitor.

• butorphanol

  doxylamine and butorphanol both increase sedation. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and doxylamine both increase sedation. 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).

• carisoprodol

  doxylamine and carisoprodol both increase sedation. Use Caution/Monitor.

• cenobamate

  cenobamate, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate and doxylamine both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  doxylamine and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorzoxazone

  doxylamine and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cinnarizine

  cinnarizine and doxylamine both increase sedation. Use Caution/Monitor.

• clemastine

  clemastine and doxylamine both increase sedation. Use Caution/Monitor.

• clobazam

  doxylamine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  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

  doxylamine and clomipramine both increase sedation. Use Caution/Monitor.

• 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).

• clonazepam

  clonazepam and doxylamine both increase sedation. Use Caution/Monitor.

• clonidine

  clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clorazepate

  clorazepate and doxylamine both increase sedation. Use Caution/Monitor.

• clozapine

  doxylamine and clozapine both increase sedation. Use Caution/Monitor.

• cocaine topical

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

• codeine

  doxylamine and codeine both increase sedation. Use Caution/Monitor.

• cyclizine

  cyclizine and doxylamine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  doxylamine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and doxylamine both increase sedation. Use Caution/Monitor.

• dantrolene

  doxylamine and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone topical

  acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  doxylamine 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

  doxylamine and desipramine both increase sedation. Use Caution/Monitor.

• 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

  doxylamine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  dexchlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  doxylamine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine and doxylamine both increase sedation. Use Caution/Monitor.

• dextroamphetamine

  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

  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).
  
  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. .

• dextromoramide

  doxylamine and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  doxylamine and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  diazepam and doxylamine both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  diazepam intranasal, doxylamine. 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 doxylamine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  doxylamine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• 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.

• dimenhydrinate

  dimenhydrinate and doxylamine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  diphenhydramine and doxylamine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  doxylamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

  doxylamine and dipipanone both increase sedation. Use Caution/Monitor.

• dopexamine

  doxylamine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  doxylamine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  doxylamine and doxepin both increase sedation. Use Caution/Monitor.

• droperidol

  doxylamine and droperidol both increase sedation. Use Caution/Monitor.

• eletriptan

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

• eltrombopag

  eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• ergotamine

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

• esketamine intranasal

  esketamine intranasal, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• estazolam

  estazolam and doxylamine both increase sedation. Use Caution/Monitor.

• ethanol

  doxylamine and ethanol both increase sedation. Use Caution/Monitor.

• etomidate

  etomidate and doxylamine both increase sedation. Use Caution/Monitor.

• exenatide injectable solution

  exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• fenfluramine

  doxylamine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• finerenone

  acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• 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).

• flibanserin

  doxylamine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• fluphenazine

  doxylamine and fluphenazine both increase sedation. Use Caution/Monitor.

• 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).

• imatinib

  imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.

• flurazepam

  flurazepam and doxylamine both increase sedation. Use Caution/Monitor.

• gabapentin

  gabapentin, doxylamine. 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, doxylamine. 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.

• ganaxolone

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

• gotu kola

  gotu kola increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• haloperidol

  doxylamine and haloperidol both increase sedation. Use Caution/Monitor.

• hawthorn

  hawthorn increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hops

  hops increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hyaluronidase

  doxylamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

• hydromorphone

  doxylamine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and doxylamine both increase sedation. Use Caution/Monitor.

• iloperidone

  doxylamine and iloperidone both increase sedation. Use Caution/Monitor.

• imipramine

  doxylamine and imipramine both increase sedation. Use Caution/Monitor.

• isavuconazonium sulfate

  acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isoniazid

  dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

• L-tryptophan

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

• ivacaftor

  acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• kava

  kava increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  ketamine and doxylamine both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

  doxylamine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lasmiditan

  lasmiditan, doxylamine. 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

  acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

• letermovir

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

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levorphanol

  doxylamine and levorphanol both increase sedation. Use Caution/Monitor.

• lithium

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

• lixisenatide

  lixisenatide will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

  doxylamine and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  doxylamine and lofexidine both increase sedation. Use Caution/Monitor.

• lomitapide

  acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• loprazolam

  loprazolam and doxylamine both increase sedation. Use Caution/Monitor.

• lorazepam

  lorazepam and doxylamine both increase sedation. Use Caution/Monitor.

• lormetazepam

  lormetazepam and doxylamine both increase sedation. 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).
  
  doxylamine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  doxylamine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  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.

• lurasidone

  lurasidone, doxylamine. 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.

• 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).

• maprotiline

  doxylamine and maprotiline both increase sedation. Use Caution/Monitor.

• marijuana

  doxylamine and marijuana both increase sedation. Use Caution/Monitor.

• melatonin

  doxylamine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  doxylamine and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  doxylamine and meprobamate both increase sedation. Use Caution/Monitor.

• metaxalone

  doxylamine and metaxalone both increase sedation. Use Caution/Monitor.

• methadone

  doxylamine and methadone both increase sedation. Use Caution/Monitor.

• methocarbamol

  doxylamine and methocarbamol both increase sedation. Use Caution/Monitor.

• methylenedioxymethamphetamine

  doxylamine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midazolam

  midazolam and doxylamine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• mipomersen

  mipomersen, acetaminophen. 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

  doxylamine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  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

  doxylamine and morphine both increase sedation. Use Caution/Monitor.

• morphine

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

• motherwort

  doxylamine and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  doxylamine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  doxylamine and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  doxylamine and nalbuphine both increase sedation. Use Caution/Monitor.

• naratriptan

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

• nortriptyline

  doxylamine and nortriptyline both increase sedation. Use Caution/Monitor.

• olanzapine

  doxylamine and olanzapine both increase sedation. Use Caution/Monitor.
  
  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

  oliceridine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• 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).

• opium tincture

  doxylamine and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

  doxylamine and orphenadrine both increase sedation. Use Caution/Monitor.

• oxazepam

  oxazepam and doxylamine both increase sedation. Use Caution/Monitor.

• oxycodone

  doxylamine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  doxylamine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  doxylamine and paliperidone both increase sedation. Use Caution/Monitor.

• 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.

• papaveretum

  doxylamine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  doxylamine and papaverine both increase sedation. Use Caution/Monitor.

• passion flower

  passion flower increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• 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.
  
  doxylamine and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  pentobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• 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).

• perphenazine

  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• phenelzine

  phenelzine increases effects of doxylamine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenobarbital

  phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• phenylephrine PO

  doxylamine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• pholcodine

  doxylamine and pholcodine both increase sedation. Use Caution/Monitor.

• 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).
  
  doxylamine and pimozide both increase sedation. Use Caution/Monitor.

• pregabalin

  pregabalin, doxylamine. 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.

• 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).

• primidone

  primidone and doxylamine both increase sedation. Use Caution/Monitor.

• prochlorperazine

  doxylamine and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine and doxylamine both increase sedation. Use Caution/Monitor.

• propofol

  propofol and doxylamine both increase sedation. Use Caution/Monitor.

• propylhexedrine

  doxylamine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protriptyline

  doxylamine and protriptyline both increase sedation. Use Caution/Monitor.

• quazepam

  quazepam and doxylamine both increase sedation. Use Caution/Monitor.

• quetiapine

  doxylamine and quetiapine both increase sedation. Use Caution/Monitor.

• quinidine

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

• ramelteon

  doxylamine and ramelteon both increase sedation. Use Caution/Monitor.

• remimazolam

  remimazolam, doxylamine. 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.

• risperidone

  doxylamine and risperidone both increase sedation. Use Caution/Monitor.
  
  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.

• scullcap

  doxylamine and scullcap both increase sedation. Use Caution/Monitor.

• 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 and doxylamine both increase sedation. Use Caution/Monitor.

• sevoflurane

  sevoflurane and doxylamine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.

• stiripentol

  stiripentol, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sufentanil

  doxylamine and sufentanil both increase sedation. Use Caution/Monitor.

• 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.

• tapentadol

  doxylamine and tapentadol both increase sedation. Use Caution/Monitor.

• tazemetostat

  acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• temazepam

  temazepam and doxylamine both increase sedation. Use Caution/Monitor.

• tetracaine

  tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  doxylamine and thioridazine both increase sedation. Use Caution/Monitor.

• 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).
  
  doxylamine and thiothixene both increase sedation. Use Caution/Monitor.

• tinidazole

  acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tramadol

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

• topiramate

  doxylamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  doxylamine and tramadol both increase sedation. Use Caution/Monitor.

• trazodone

  doxylamine and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  triazolam and doxylamine both increase sedation. Use Caution/Monitor.

• triclofos

  doxylamine and triclofos both increase sedation. Use Caution/Monitor.

• 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).
  
  doxylamine and trifluoperazine both increase sedation. Use Caution/Monitor.

• trimipramine

  doxylamine and trimipramine both increase sedation. 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).

• triprolidine

  triprolidine and doxylamine both increase sedation. Use Caution/Monitor.

• valerian

  valerian increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• warfarin

  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• xylometazoline

  doxylamine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zolmitriptan

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

Minor (74)

• acetazolamide

  acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• albiglutide

  albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• amiodarone

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

• antithrombin alfa

  acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• argatroban

  acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

• asenapine

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

• ashwagandha

  ashwagandha increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• bemiparin

  acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• bivalirudin

  acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• carbamazepine

  carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• cholestyramine

  cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cimetidine

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

• clonazepam

  clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• colestipol

  colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• dalteparin

  acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• darifenacin

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

• diazepam

  diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• diphenhydramine

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

• disulfiram

  disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• dronedarone

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

• enoxaparin

  acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• ethanol

  ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethosuximide

  ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• eucalyptus

  doxylamine and eucalyptus both increase sedation. Minor/Significance Unknown.

• felbamate

  felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• fondaparinux

  acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• fosphenytoin

  fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• green tea

  green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• haloperidol

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

• heparin

  acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• imatinib

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

• isoniazid

  isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• lacosamide

  lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lamotrigine

  lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levetiracetam

  levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• liraglutide

  liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• lorazepam

  lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• methsuximide

  methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• metoclopramide

  metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• nettle

  nettle increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nilotinib

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

• oxcarbazepine

  oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. 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.

• phenindione

  acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• phenytoin

  phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• primidone

  primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• propafenone

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

• protamine

  acetaminophen increases effects of protamine by unknown mechanism. 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.

• rifabutin

  rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ritonavir

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

• rufinamide

  rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ruxolitinib

  acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

  doxylamine and sage both increase sedation. Minor/Significance Unknown.

• Siberian ginseng

  Siberian ginseng increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• 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.

• tiagabine

  tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• acetazolamide

  Minor (1)acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• albiglutide

  Minor (1)albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• alfentanil

  Monitor Closely (1)doxylamine and alfentanil both increase sedation. Use Caution/Monitor.

• almotriptan

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

• alprazolam

  Monitor Closely (1)alprazolam and doxylamine both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)doxylamine 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.

• amiodarone

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

• amitriptyline

  Monitor Closely (1)doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• amobarbital

  Monitor Closely (1)amobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (1)doxylamine and amoxapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amoxapine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• amphetamine

  Monitor Closely (1)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. .

• antithrombin alfa

  Minor (1)acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  Minor (1)acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• apomorphine

  Monitor Closely (1)doxylamine and apomorphine both increase sedation. Use Caution/Monitor.

• argatroban

  Minor (1)acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

• aripiprazole

  Monitor Closely (2)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).
  
  doxylamine and aripiprazole both increase sedation. Use Caution/Monitor.

• 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.

• ashwagandha

  Minor (1)ashwagandha increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atogepant

  Monitor Closely (1)acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• avapritinib

  Monitor Closely (1)acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• axitinib

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

• azelastine

  Monitor Closely (1)azelastine and doxylamine both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)doxylamine and baclofen both increase sedation. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (1)doxylamine and belladonna and opium both increase sedation. Use Caution/Monitor.

• bemiparin

  Minor (1)acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• benperidol

  Monitor Closely (1)doxylamine and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (1)benzhydrocodone/acetaminophen, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• benzphetamine

  Monitor Closely (1)doxylamine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bivalirudin

  Minor (1)acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• brexanolone

  Monitor Closely (1)brexanolone, doxylamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brimonidine

  Minor (1)brimonidine increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brompheniramine

  Monitor Closely (1)brompheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• bupivacaine implant

  Monitor Closely (1)acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

  Monitor Closely (1)doxylamine and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (1)doxylamine and buprenorphine buccal both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  Monitor Closely (1)doxylamine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• 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.

• busulfan

  Monitor Closely (1)acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• butabarbital

  Monitor Closely (1)butabarbital and doxylamine both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital and doxylamine both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (1)doxylamine and butorphanol both increase sedation. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)doxylamine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• carbamazepine

  Minor (1)carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and doxylamine both increase sedation. Use Caution/Monitor.

• 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).

• carisoprodol

  Monitor Closely (1)doxylamine and carisoprodol both increase sedation. Use Caution/Monitor.

• celecoxib

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

• cenobamate

  Monitor Closely (1)cenobamate, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloral hydrate

  Monitor Closely (1)chloral hydrate and doxylamine both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.

• chloroquine

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

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (1)doxylamine and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorzoxazone

  Monitor Closely (1)doxylamine and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cholestyramine

  Minor (1)cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cimetidine

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

• cinnarizine

  Monitor Closely (1)cinnarizine and doxylamine both increase sedation. Use Caution/Monitor.

• 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.

• clemastine

  Monitor Closely (1)clemastine and doxylamine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (2)doxylamine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  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

  Monitor Closely (1)doxylamine and clomipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• clonazepam

  Monitor Closely (1)clonazepam and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• clonidine

  Monitor Closely (1)clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clorazepate

  Monitor Closely (1)clorazepate and doxylamine both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (2)doxylamine and clozapine both increase sedation. Use Caution/Monitor.
  
  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

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

• codeine

  Monitor Closely (1)doxylamine and codeine both increase sedation. Use Caution/Monitor.

• colestipol

  Minor (1)colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (1)cyclizine and doxylamine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (1)doxylamine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and doxylamine both increase sedation. Use Caution/Monitor.

• dalteparin

  Minor (1)acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• dantrolene

  Monitor Closely (1)doxylamine and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone topical

  Monitor Closely (1)acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  Monitor Closely (1)doxylamine 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.

• darifenacin

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

• desipramine

  Monitor Closely (1)doxylamine and desipramine both increase sedation. Use Caution/Monitor.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.

• deutetrabenazine

  Monitor Closely (1)doxylamine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  doxylamine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and doxylamine both increase sedation. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (1)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

  Monitor Closely (2)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).

• dextromoramide

  Monitor Closely (1)doxylamine and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)doxylamine and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diazepam and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• difelikefalin

  Monitor Closely (1)difelikefalin and doxylamine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)doxylamine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• 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.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and doxylamine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (1)diphenhydramine and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

  Monitor Closely (1)doxylamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)doxylamine and dipipanone both increase sedation. Use Caution/Monitor.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• dopexamine

  Monitor Closely (1)doxylamine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)doxylamine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  Monitor Closely (1)doxylamine and doxepin both increase sedation. Use Caution/Monitor.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.

• droperidol

  Monitor Closely (1)doxylamine and droperidol both increase sedation. Use Caution/Monitor.

• 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.

• eltrombopag

  Monitor Closely (1)eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• enoxaparin

  Minor (1)acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• 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.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• estazolam

  Monitor Closely (1)estazolam and doxylamine both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)doxylamine and ethanol both increase sedation. Use Caution/Monitor.Minor (2)ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethosuximide

  Minor (1)ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• etomidate

  Monitor Closely (1)etomidate and doxylamine both increase sedation. Use Caution/Monitor.

• eucalyptus

  Minor (1)doxylamine and eucalyptus both increase sedation. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  Monitor Closely (1)exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• felbamate

  Minor (1)felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• fenfluramine

  Monitor Closely (3)doxylamine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• fentanyl

  Serious - Use Alternative (1)fentanyl, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  Serious - Use Alternative (1)fentanyl transdermal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  Serious - Use Alternative (1)fentanyl transmucosal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• finerenone

  Monitor Closely (1)acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  Monitor Closely (2)doxylamine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• 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 (2)doxylamine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  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).

• flurazepam

  Monitor Closely (1)flurazepam and doxylamine both increase sedation. Use Caution/Monitor.

• fluvoxamine

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

• fondaparinux

  Minor (1)acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• fosphenytoin

  Minor (1)fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• frovatriptan

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

• gabapentin

  Monitor Closely (1)gabapentin, doxylamine. 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

  Monitor Closely (1)gabapentin enacarbil, doxylamine. 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.

• ganaxolone

  Monitor Closely (1)doxylamine and ganaxolone both increase sedation. Use Caution/Monitor.

• gotu kola

  Monitor Closely (1)gotu kola increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• 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.

• green tea

  Minor (1)green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• haloperidol

  Monitor Closely (2)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).
  
  doxylamine and haloperidol both increase sedation. Use Caution/Monitor.Minor (1)haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• hawthorn

  Monitor Closely (1)hawthorn increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• heparin

  Minor (1)acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• hops

  Monitor Closely (1)hops increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hyaluronidase

  Monitor Closely (1)doxylamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .

• hydrocodone

  Serious - Use Alternative (1)hydrocodone, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• hydromorphone

  Monitor Closely (1)doxylamine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and doxylamine both increase sedation. Use Caution/Monitor.

• iloperidone

  Monitor Closely (2)doxylamine and iloperidone both increase sedation. Use Caution/Monitor.
  
  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

  Monitor Closely (1)imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.Minor (1)imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imipramine

  Monitor Closely (1)doxylamine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)imipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• isavuconazonium sulfate

  Monitor Closely (1)acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Contraindicated (1)isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.Serious - Use Alternative (1)isocarboxazid increases effects of doxylamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• isoniazid

  Monitor Closely (2)dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.Minor (1)isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• ivacaftor

  Monitor Closely (1)acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• kava

  Monitor Closely (1)kava increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (1)ketamine and doxylamine both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

  Monitor Closely (1)doxylamine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

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

• lacosamide

  Minor (1)lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lamotrigine

  Minor (1)lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lasmiditan

  Monitor Closely (1)lasmiditan, doxylamine. 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

  Monitor Closely (1)acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.Serious - Use Alternative (1)lemborexant, doxylamine. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.

• letermovir

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

• levetiracetam

  Minor (1)levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levomilnacipran

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

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (2)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levorphanol

  Monitor Closely (1)doxylamine and levorphanol both increase sedation. Use Caution/Monitor.

• 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.

• liraglutide

  Minor (1)liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• lithium

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

• lixisenatide

  Monitor Closely (1)lixisenatide will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

  Monitor Closely (1)doxylamine and lofepramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• lofexidine

  Monitor Closely (1)doxylamine and lofexidine both increase sedation. Use Caution/Monitor.

• lomitapide

  Monitor Closely (1)acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loprazolam

  Monitor Closely (1)loprazolam and doxylamine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (1)lorazepam and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lorcaserin

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

• lormetazepam

  Monitor Closely (1)lormetazepam and doxylamine both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (2)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).
  
  doxylamine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)doxylamine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  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 (2)lurasidone, doxylamine. 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.
  
  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

  Monitor Closely (1)doxylamine and maprotiline both increase sedation. Use Caution/Monitor.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

  Monitor Closely (1)doxylamine and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• melatonin

  Monitor Closely (1)doxylamine and melatonin both increase sedation. Use Caution/Monitor.

• memantine

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

• meperidine

  Monitor Closely (1)doxylamine and meperidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• meprobamate

  Monitor Closely (1)doxylamine and meprobamate both increase sedation. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)doxylamine and metaxalone both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (1)doxylamine and methadone both increase sedation. Use Caution/Monitor.

• methocarbamol

  Monitor Closely (1)doxylamine and methocarbamol both increase sedation. Use Caution/Monitor.

• methsuximide

  Minor (1)methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• methylene blue

  Serious - Use Alternative (2)methylene blue and doxylamine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
  
  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.

• methylenedioxymethamphetamine

  Monitor Closely (1)doxylamine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metoclopramide

  Minor (1)metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)doxylamine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (1)midazolam and doxylamine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)midazolam intranasal, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• milnacipran

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

• mipomersen

  Monitor Closely (1)mipomersen, acetaminophen. 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

  Monitor Closely (2)doxylamine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  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 (2)dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  doxylamine and morphine both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)doxylamine and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  Monitor Closely (1)doxylamine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)doxylamine and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)doxylamine and nalbuphine both increase sedation. Use Caution/Monitor.

• 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.

• nettle

  Minor (1)nettle increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nilotinib

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

• nortriptyline

  Monitor Closely (1)doxylamine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• olanzapine

  Monitor Closely (2)doxylamine and olanzapine both increase sedation. Use Caution/Monitor.
  
  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

  Monitor Closely (1)oliceridine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• olopatadine intranasal

  Serious - Use Alternative (1)doxylamine 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.

• opium tincture

  Monitor Closely (1)doxylamine and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (1)doxylamine and orphenadrine both increase sedation. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)oxazepam and doxylamine both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Minor (1)oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  Minor (1)oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Minor (1)oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Minor (1)oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (1)doxylamine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (1)doxylamine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  Monitor Closely (2)doxylamine and paliperidone both increase sedation. Use Caution/Monitor.
  
  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.

• papaveretum

  Monitor Closely (1)doxylamine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)doxylamine and papaverine both increase sedation. Use Caution/Monitor.

• 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.

• passion flower

  Monitor Closely (1)passion flower increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• 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 (2)dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  doxylamine and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (1)pentobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (2)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).
  
  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• pexidartinib

  Serious - Use Alternative (1)acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• phenelzine

  Contraindicated (1)phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.Monitor Closely (1)phenelzine increases effects of doxylamine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenindione

  Minor (1)acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

  Monitor Closely (1)phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• phenylephrine PO

  Monitor Closely (1)doxylamine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Minor (1)phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• pholcodine

  Monitor Closely (1)doxylamine and pholcodine both increase sedation. Use Caution/Monitor.

• 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 (2)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).
  
  doxylamine and pimozide both increase sedation. Use Caution/Monitor.

• pregabalin

  Monitor Closely (1)pregabalin, doxylamine. 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.

• pretomanid

  Serious - Use Alternative (1)acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• primidone

  Monitor Closely (1)primidone and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• procarbazine

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

• prochlorperazine

  Monitor Closely (1)doxylamine and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)promethazine and doxylamine both increase sedation. Use Caution/Monitor.

• propafenone

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

• propofol

  Monitor Closely (1)propofol and doxylamine both increase sedation. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (1)doxylamine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  Minor (1)acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

• protriptyline

  Monitor Closely (1)doxylamine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• quazepam

  Monitor Closely (1)quazepam and doxylamine both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)doxylamine and quetiapine both increase sedation. Use Caution/Monitor.
  
  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.

• ramelteon

  Monitor Closely (1)doxylamine and ramelteon both increase sedation. 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.

• remimazolam

  Monitor Closely (1)remimazolam, doxylamine. 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.

• rifabutin

  Minor (1)rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  Minor (1)rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• risperidone

  Monitor Closely (2)doxylamine and risperidone both increase sedation. Use Caution/Monitor.
  
  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.

• rufinamide

  Minor (1)rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ruxolitinib

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• sage

  Minor (1)doxylamine and sage both increase sedation. Minor/Significance Unknown.

• SAMe

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

• scullcap

  Monitor Closely (1)doxylamine and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• 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.

• selinexor

  Serious - Use Alternative (1)selinexor, doxylamine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• 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.

• sevoflurane

  Monitor Closely (1)sevoflurane and doxylamine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• sodium oxybate

  Serious - Use Alternative (1)doxylamine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• St John's Wort

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

• stiripentol

  Monitor Closely (1)stiripentol, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sufentanil

  Monitor Closely (1)doxylamine and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• 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.

• tapentadol

  Monitor Closely (1)doxylamine and tapentadol both increase sedation. Use Caution/Monitor.

• tazemetostat

  Monitor Closely (1)acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• temazepam

  Monitor Closely (1)temazepam and doxylamine both increase sedation. Use Caution/Monitor.

• tetracaine

  Monitor Closely (1)tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  Monitor Closely (1)doxylamine and thioridazine both increase sedation. Use Caution/Monitor.Minor (1)thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (2)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).
  
  doxylamine and thiothixene both increase sedation. Use Caution/Monitor.

• tiagabine

  Minor (1)tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• tinidazole

  Monitor Closely (1)acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

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

• topiramate

  Monitor Closely (1)doxylamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• tramadol

  Monitor Closely (2)doxylamine and tramadol both increase sedation. Use Caution/Monitor.
  
  dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• tranylcypromine

  Contraindicated (1)tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.Serious - Use Alternative (1)tranylcypromine increases effects of doxylamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• trazodone

  Monitor Closely (1)doxylamine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• triazolam

  Monitor Closely (1)triazolam and doxylamine both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)doxylamine and triclofos both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)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).
  
  doxylamine and trifluoperazine both increase sedation. Use Caution/Monitor.

• trimipramine

  Monitor Closely (1)doxylamine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• triprolidine

  Monitor Closely (1)triprolidine and doxylamine both increase sedation. Use Caution/Monitor.

• valerian

  Monitor Closely (1)valerian increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.Serious - Use Alternative (1)valerian and doxylamine both increase sedation. Avoid or Use Alternate Drug.

• valproic acid

  Minor (1)valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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. .

• warfarin

  Monitor Closely (1)acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (1)doxylamine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  Monitor Closely (1)doxylamine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)doxylamine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  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.

• zonisamide

  Minor (1)zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

• zotepine

  Monitor Closely (1)doxylamine and zotepine both increase sedation. Use Caution/Monitor.