acetaminophen/doxylamine/dextromethorphan/phenylephrine (OTC)

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

2 caps PO q4hr PRN; not to exceed 12 caps/day

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

<12 Years

• Ask a pediatrician

≥12 Years

• 2 caps PO q4hr PRN; not to exceed 12 caps/day

Contraindicated (7)

• iobenguane I 123

  phenylephrine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

• isocarboxazid

  isocarboxazid increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• linezolid

  linezolid increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• phenelzine

  phenelzine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• procarbazine

  procarbazine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• selegiline transdermal

  selegiline transdermal increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• tranylcypromine

  tranylcypromine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

Serious - Use Alternative (37)

• amitriptyline

  amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• amoxapine

  amoxapine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• 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.

• cabergoline

  cabergoline, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• 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.

• clomipramine

  clomipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• desflurane

  desflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.
  
  desflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• desipramine

  desipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dihydroergotamine

  dihydroergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dihydroergotamine intranasal

  dihydroergotamine intranasal, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• doxapram

  doxapram increases effects of phenylephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

• doxepin

  doxepin, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• ergoloid mesylates

  ergoloid mesylates, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ergotamine

  ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ether

  ether increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• etomidate

  etomidate increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• 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.

• 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, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• 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. .

• isoflurane

  isoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• 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.

• lofepramine

  lofepramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• 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.

• maprotiline

  maprotiline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methoxyflurane

  methoxyflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• 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

• methylergonovine

  methylergonovine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• 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.

• nortriptyline

  nortriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• 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.

• 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.

• propofol

  propofol increases levels of phenylephrine by decreasing metabolism. Contraindicated.

Monitor Closely (273)

• acrivastine

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

• albuterol

  albuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  albuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• alfentanil

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

• alprazolam

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

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

• amisulpride

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

• amitriptyline

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

• amobarbital

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

• amoxapine

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

• 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.

• arformoterol

  arformoterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  arformoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• aripiprazole

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

• armodafinil

  armodafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• asenapine

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

• asenapine transdermal

  asenapine transdermal and doxylamine both increase sedation. Use Caution/Monitor.

• atogepant

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

• atomoxetine

  atomoxetine, phenylephrine. Other (see comment). Use Caution/Monitor. Comment: Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine.

• avapritinib

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

• axitinib

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

• azelastine

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

• baclofen

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

• belladonna and opium

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

• belladonna and opium

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

• benperidol

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

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and doxylamine both increase sedation. Use Caution/Monitor.

• benzphetamine

  benzphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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.

• brexpiprazole

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

• brimonidine

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

• brivaracetam

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

• bromocriptine

  bromocriptine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

• brompheniramine

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

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  buprenorphine subdermal implant and doxylamine 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.

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

• butalbital

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

• butorphanol

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

• caffeine

  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• carbinoxamine

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

• carbinoxamine

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

• 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.
  
  chloral hydrate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

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

• chlorpheniramine

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

• chlorpromazine

  doxylamine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpromazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorzoxazone

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

• cinnarizine

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

• cinnarizine

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

• clemastine

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

• clomipramine

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

• clomipramine

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

• clonazepam

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

• clorazepate

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

• clozapine

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

• codeine

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

• cyclizine

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

• cyclobenzaprine

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

• cyproheptadine

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

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexchlorpheniramine

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

• dexfenfluramine

  dexfenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  doxylamine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

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

• dexmethylphenidate

  dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dextromoramide

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

• dextroamphetamine

  dextroamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dextroamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diethylpropion

  diethylpropion and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  diethylpropion and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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.
  
  difenoxin hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dimenhydrinate

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

• diphenhydramine

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

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

  dobutamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dobutamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopexamine

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

• dopamine

  dopamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dopamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopexamine

  dopexamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dopexamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dosulepin

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

• doxepin

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

• droperidol

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

• droxidopa

  phenylephrine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• eltrombopag

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

• esketamine intranasal

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

• ephedrine

  ephedrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  ephedrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  ephedrine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

• epinephrine

  epinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  epinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine inhaled

  phenylephrine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  epinephrine racemic and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  epinephrine racemic and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• estazolam

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

• ethanol

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

  fenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  fenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• fenfluramine

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

• 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.

• 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.
  
  fluphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  fluphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

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

• formoterol

  formoterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  formoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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

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

• hydralazine

  hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

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

• hydroxyzine

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

• iloperidone

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

• imipramine

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

• indacaterol, inhaled

  phenylephrine increases effects of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

• isavuconazonium sulfate

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

• isoniazid

  isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

• 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.

• insulin degludec

  phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin degludec/insulin aspart

  phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin inhaled

  phenylephrine decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• isoproterenol

  isoproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  isoproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• ketamine

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

• ketotifen, ophthalmic

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

• levalbuterol

  levalbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  levalbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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

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

• lisdexamfetamine

  lisdexamfetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  lisdexamfetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• lixisenatide (DSC)

  lixisenatide (DSC) 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.

• lofepramine

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

• lofexidine

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

• lorazepam

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• 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.

• maprotiline

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

• maprotiline

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

• marijuana

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

• melatonin

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

• meperidine

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

• meprobamate

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

• metaproterenol

  metaproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  metaproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• metaxalone

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

• methadone

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

• methamphetamine

  methamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  methamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• methocarbamol

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

• methyldopa

  methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

• methylenedioxymethamphetamine

  methylenedioxymethamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  doxylamine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• midazolam

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

• midodrine

  midodrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  midodrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

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

• modafinil

  modafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• morphine

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

• morphine

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nadolol

  nadolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• nalbuphine

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

• nalbuphine

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

• norepinephrine

  norepinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  norepinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• nortriptyline

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

• olanzapine

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

• 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.

• olodaterol inhaled

  phenylephrine and olodaterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Caution with coadministration of adrenergic drugs by any route because of additive sympathetic effects

• opium tincture

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

• orphenadrine

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

• oxazepam

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

• oxazepam

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

• oxycodone

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

• oxymetazoline topical

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

• oxymorphone

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

• oxymorphone

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

• oxytocin

  oxytocin increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor.

• paliperidone

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

• papaveretum

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

• papaverine

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

• pentazocine

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

• passion flower

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

• pentazocine

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

• pentobarbital

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

• perphenazine

  perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  phendimetrazine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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.
  
  phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phentermine

  phentermine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phentermine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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.
  
  pholcodine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimozide

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

• pindolol

  pindolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• 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.

• pirbuterol

  pirbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  pirbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• primidone

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

• prochlorperazine

  doxylamine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  prochlorperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promazine

  promazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promethazine

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

• promethazine

  promethazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• propofol

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

• propranolol

  propranolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• propylhexedrine

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

• propylhexedrine

  phenylephrine and propylhexedrine both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and propylhexedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• protriptyline

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

• pseudoephedrine

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

• quazepam

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

• quazepam

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

• quetiapine

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

• ramelteon

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

• rasagiline

  rasagiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• 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

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

• safinamide

  phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

• scullcap

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

• salmeterol

  salmeterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  salmeterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• scullcap

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

• secobarbital

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

• selegiline

  selegiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• sevoflurane

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

• serdexmethylphenidate/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  serdexmethylphenidate/dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• shepherd's purse

  doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• solriamfetol

  phenylephrine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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

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

• tapentadol

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

• terbutaline

  terbutaline and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  terbutaline and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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.

• thioridazine

  thioridazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  thioridazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• thiothixene

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

• timolol

  timolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• tinidazole

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

• topiramate

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

• topiramate

  topiramate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• tramadol

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

• trazodone

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

• triazolam

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

• triclofos

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

• trifluoperazine

  doxylamine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  trifluoperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• trimipramine

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

• triprolidine

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

  phenylephrine and xylometazoline both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

Minor (62)

• 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.

• alfuzosin

  alfuzosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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.

• cholestyramine

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

• desmopressin

  desmopressin increases effects of phenylephrine by pharmacodynamic synergism. Minor/Significance Unknown.

• diazepam

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

• disulfiram

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

• doxazosin

  doxazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. 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

  eucalyptus increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  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).

• heparin

  acetaminophen increases effects of heparin by unknown mechanism. 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.

• 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.

• moxisylyte

  moxisylyte, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• nettle

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

• 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.

• 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.

• phenoxybenzamine

  phenoxybenzamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phentolamine

  phentolamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phenytoin

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

• prazosin

  prazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• primidone

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

• protamine

  acetaminophen increases effects of protamine by unknown mechanism. 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.

• 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

  sage increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  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.

• silodosin

  silodosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• terazosin

  terazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• tiagabine

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

• acetazolamide

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

• acrivastine

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

• albiglutide

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

• albuterol

  Monitor Closely (2)albuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  albuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• alfentanil

  Monitor Closely (2)doxylamine and alfentanil both increase sedation. Use Caution/Monitor.
  
  alfentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfuzosin

  Minor (1)alfuzosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• alprazolam

  Monitor Closely (2)alprazolam and doxylamine both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• amisulpride

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

• amitriptyline

  Monitor Closely (2)doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• amobarbital

  Monitor Closely (2)amobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (2)amoxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and amoxapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amoxapine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• 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.

• arformoterol

  Monitor Closely (2)arformoterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  arformoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• argatroban

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

• aripiprazole

  Monitor Closely (2)aripiprazole increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and aripiprazole both increase sedation. Use Caution/Monitor.

• armodafinil

  Monitor Closely (1)armodafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• asenapine

  Monitor Closely (1)asenapine and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• asenapine transdermal

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

• 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.

• atomoxetine

  Monitor Closely (1)atomoxetine, phenylephrine. Other (see comment). Use Caution/Monitor. Comment: Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine.

• avapritinib

  Monitor Closely (2)acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  avapritinib and doxylamine both increase sedation. 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 (2)azelastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)belladonna and opium increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)benperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)benzhydrocodone/acetaminophen and doxylamine both increase sedation. Use Caution/Monitor.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 (3)doxylamine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both decrease sedation. 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.

• brexpiprazole

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

• brimonidine

  Monitor Closely (1)brimonidine and doxylamine both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

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

• bromocriptine

  Monitor Closely (1)bromocriptine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

• brompheniramine

  Monitor Closely (2)brompheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)doxylamine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• buprenorphine subdermal implant

  Monitor Closely (1)buprenorphine subdermal implant and doxylamine 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.

• 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 (2)butabarbital and doxylamine both increase sedation. Use Caution/Monitor.
  
  butabarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butalbital

  Monitor Closely (2)butalbital and doxylamine both increase sedation. Use Caution/Monitor.
  
  butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butorphanol

  Monitor Closely (2)butorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and butorphanol both increase sedation. Use Caution/Monitor.

• cabergoline

  Serious - Use Alternative (1)cabergoline, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• caffeine

  Monitor Closely (1)caffeine and phenylephrine both decrease 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 (2)carbinoxamine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  carbinoxamine and doxylamine both increase sedation. Use Caution/Monitor.

• carisoprodol

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

• cenobamate

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

• chloral hydrate

  Monitor Closely (2)chloral hydrate and doxylamine both increase sedation. Use Caution/Monitor.
  
  chloral hydrate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (2)chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (3)doxylamine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpromazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• cinnarizine

  Monitor Closely (2)cinnarizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  cinnarizine and doxylamine both increase sedation. Use Caution/Monitor.

• clemastine

  Monitor Closely (2)clemastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clemastine and doxylamine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)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).

• clomipramine

  Monitor Closely (2)clomipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and clomipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clomipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• clonazepam

  Monitor Closely (2)clonazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  clonazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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 (2)clorazepate and doxylamine both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clozapine

  Monitor Closely (2)clozapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and clozapine both increase sedation. Use Caution/Monitor.

• codeine

  Monitor Closely (2)doxylamine and codeine both increase sedation. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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 (2)cyclizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)cyproheptadine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• desflurane

  Serious - Use Alternative (2)desflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.
  
  desflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• desipramine

  Monitor Closely (2)doxylamine and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)desipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• desmopressin

  Minor (1)desmopressin increases effects of phenylephrine by pharmacodynamic synergism. Minor/Significance Unknown.

• deutetrabenazine

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

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexchlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (3)doxylamine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (2)dexmedetomidine and doxylamine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (2)dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (2)dextroamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dextroamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dextromoramide

  Monitor Closely (2)doxylamine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  Monitor Closely (2)doxylamine and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• diethylpropion

  Monitor Closely (2)diethylpropion and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  diethylpropion and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• difelikefalin

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

• difenoxin hcl

  Monitor Closely (2)doxylamine and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  difenoxin hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dihydroergotamine

  Serious - Use Alternative (1)dihydroergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)dihydroergotamine intranasal, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dimenhydrinate

  Monitor Closely (2)dimenhydrinate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dimenhydrinate and doxylamine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)diphenhydramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine and doxylamine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (2)diphenoxylate hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (2)doxylamine and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• disulfiram

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

• dobutamine

  Monitor Closely (2)dobutamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dobutamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopamine

  Monitor Closely (2)dopamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dopamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopexamine

  Monitor Closely (3)doxylamine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  dopexamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dosulepin

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

• doxapram

  Serious - Use Alternative (1)doxapram increases effects of phenylephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

• doxazosin

  Minor (1)doxazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• doxepin

  Monitor Closely (2)doxepin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)doxepin, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• droperidol

  Monitor Closely (2)droperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and droperidol both increase sedation. Use Caution/Monitor.

• droxidopa

  Monitor Closely (1)phenylephrine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• 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.

• ephedrine

  Monitor Closely (3)ephedrine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.
  
  ephedrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  ephedrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine

  Monitor Closely (2)epinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  epinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine inhaled

  Monitor Closely (1)phenylephrine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (2)epinephrine racemic and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  epinephrine racemic and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• ergoloid mesylates

  Serious - Use Alternative (1)ergoloid mesylates, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ergotamine

  Serious - Use Alternative (1)ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• esketamine intranasal

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

• estazolam

  Monitor Closely (2)estazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  estazolam and doxylamine both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (2)doxylamine and ethanol both increase sedation. Use Caution/Monitor.
  
  ethanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• ether

  Serious - Use Alternative (1)ether increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• 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.Serious - Use Alternative (1)etomidate increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• eucalyptus

  Minor (2)eucalyptus increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  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 and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  fenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• 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.

• fluphenazine

  Monitor Closely (3)doxylamine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  fluphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  fluphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• flurazepam

  Monitor Closely (2)flurazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  flurazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fondaparinux

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

• formoterol

  Monitor Closely (2)formoterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  formoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• fosphenytoin

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

• 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.

• 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)haloperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and haloperidol both increase sedation. Use Caution/Monitor.

• 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. .

• hydralazine

  Monitor Closely (1)hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

• 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 (2)doxylamine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (2)hydroxyzine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  hydroxyzine and doxylamine both increase sedation. Use Caution/Monitor.

• iloperidone

  Monitor Closely (2)iloperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and iloperidone both increase sedation. Use Caution/Monitor.

• 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.

• imipramine

  Monitor Closely (2)imipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)imipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• indacaterol, inhaled

  Monitor Closely (1)phenylephrine increases effects of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

• insulin degludec

  Monitor Closely (1)phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin degludec/insulin aspart

  Monitor Closely (1)phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin inhaled

  Monitor Closely (1)phenylephrine decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• iobenguane I 123

  Contraindicated (1)phenylephrine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

• 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 increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.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. .

• isoflurane

  Serious - Use Alternative (1)isoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• isoniazid

  Monitor Closely (1)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.

• isoproterenol

  Monitor Closely (2)isoproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  isoproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• 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 (2)doxylamine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  ketotifen, ophthalmic increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• 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.

• levalbuterol

  Monitor Closely (2)levalbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  levalbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• levetiracetam

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

• 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 (2)levorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and levorphanol both increase sedation. Use Caution/Monitor.

• linezolid

  Contraindicated (1)linezolid increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• liraglutide

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

• lisdexamfetamine

  Monitor Closely (2)lisdexamfetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  lisdexamfetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC) 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 (2)doxylamine and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)lofepramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lofexidine

  Monitor Closely (2)lofexidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)loprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  loprazolam and doxylamine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (2)lorazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  lorazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lormetazepam

  Monitor Closely (2)lormetazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  lormetazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine

  Monitor Closely (2)doxylamine and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)loxapine inhaled increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)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.

• maprotiline

  Monitor Closely (2)doxylamine and maprotiline both increase sedation. Use Caution/Monitor.
  
  maprotiline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)maprotiline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• marijuana

  Monitor Closely (2)doxylamine and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• melatonin

  Monitor Closely (2)doxylamine and melatonin both increase sedation. Use Caution/Monitor.
  
  melatonin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meperidine

  Monitor Closely (2)meperidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (2)meprobamate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (2)metaproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  metaproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• metaxalone

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

• methadone

  Monitor Closely (2)doxylamine and methadone both increase sedation. Use Caution/Monitor.
  
  methadone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (2)methamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  methamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• methocarbamol

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

• methoxyflurane

  Serious - Use Alternative (1)methoxyflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• methsuximide

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

• methyldopa

  Monitor Closely (1)methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

• methylene blue

  Serious - Use Alternative (1)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

• methylenedioxymethamphetamine

  Monitor Closely (3)methylenedioxymethamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  doxylamine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• methylergonovine

  Serious - Use Alternative (1)methylergonovine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• 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 (2)midazolam and doxylamine both increase sedation. Use Caution/Monitor.
  
  midazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• midodrine

  Monitor Closely (2)midodrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  midodrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

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

• modafinil

  Monitor Closely (1)modafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• morphine

  Monitor Closely (2)doxylamine and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  Monitor Closely (2)doxylamine and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxisylyte

  Minor (1)moxisylyte, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• moxonidine

  Monitor Closely (2)moxonidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (2)nabilone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and nabilone both increase sedation. Use Caution/Monitor.

• nadolol

  Monitor Closely (1)nadolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• nalbuphine

  Monitor Closely (2)nalbuphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and nalbuphine both increase sedation. Use Caution/Monitor.

• nettle

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

• norepinephrine

  Monitor Closely (2)norepinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  norepinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (2)nortriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• olanzapine

  Monitor Closely (2)olanzapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and olanzapine both increase sedation. Use Caution/Monitor.

• 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.

• olodaterol inhaled

  Monitor Closely (1)phenylephrine and olodaterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Caution with coadministration of adrenergic drugs by any route because of additive sympathetic effects

• 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 (2)doxylamine and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orphenadrine

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

• oxazepam

  Monitor Closely (2)oxazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  oxazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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 (2)doxylamine and oxycodone both increase sedation. Use Caution/Monitor.
  
  oxycodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxymetazoline topical

  Monitor Closely (1)oxymetazoline topical and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (2)oxymorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and oxymorphone both increase sedation. Use Caution/Monitor.

• oxytocin

  Monitor Closely (1)oxytocin increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor.

• paliperidone

  Monitor Closely (2)doxylamine and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaveretum

  Monitor Closely (2)papaveretum increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

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

• passion flower

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

• pentazocine

  Monitor Closely (2)doxylamine and pentazocine both increase sedation. Use Caution/Monitor.
  
  pentazocine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (2)pentobarbital and doxylamine both increase sedation. Use Caution/Monitor.
  
  pentobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• perphenazine

  Monitor Closely (3)perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• 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.

• phendimetrazine

  Monitor Closely (2)phendimetrazine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• phenelzine

  Contraindicated (1)phenelzine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.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 (2)phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.
  
  phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• phenoxybenzamine

  Minor (1)phenoxybenzamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phentermine

  Monitor Closely (2)phentermine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phentermine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• phentolamine

  Minor (1)phentolamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• 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 (2)doxylamine and pholcodine both increase sedation. Use Caution/Monitor.
  
  pholcodine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimozide

  Monitor Closely (2)pimozide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and pimozide both increase sedation. Use Caution/Monitor.

• pindolol

  Monitor Closely (1)pindolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• pirbuterol

  Monitor Closely (2)pirbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  pirbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• prazosin

  Minor (1)prazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• 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 (2)primidone and doxylamine both increase sedation. Use Caution/Monitor.
  
  primidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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 increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• prochlorperazine

  Monitor Closely (3)doxylamine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  prochlorperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promazine

  Monitor Closely (1)promazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promethazine

  Monitor Closely (3)promethazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine and doxylamine both increase sedation. Use Caution/Monitor.
  
  promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• propofol

  Monitor Closely (2)propofol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  propofol and doxylamine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)propofol increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• propranolol

  Monitor Closely (1)propranolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• propylhexedrine

  Monitor Closely (3)phenylephrine and propylhexedrine both decrease sedation. Use Caution/Monitor.
  
  doxylamine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenylephrine and propylhexedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• protamine

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

• protriptyline

  Monitor Closely (2)doxylamine and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pseudoephedrine

  Monitor Closely (1)phenylephrine and pseudoephedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• quazepam

  Monitor Closely (2)quazepam and doxylamine both increase sedation. Use Caution/Monitor.
  
  quazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)quetiapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and quetiapine both increase sedation. Use Caution/Monitor.

• ramelteon

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

• rasagiline

  Monitor Closely (1)rasagiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• 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)risperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and risperidone both increase sedation. Use Caution/Monitor.

• 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

  Monitor Closely (1)phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

• sage

  Minor (2)sage increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  doxylamine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)salmeterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  salmeterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• scullcap

  Monitor Closely (2)scullcap increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (2)secobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  secobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• selegiline

  Monitor Closely (1)selegiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• 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.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (2)serdexmethylphenidate/dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  serdexmethylphenidate/dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sevoflurane

  Monitor Closely (1)sevoflurane and doxylamine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)sevoflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.
  
  sevoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• shepherd's purse

  Monitor Closely (2)doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• Siberian ginseng

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

• silodosin

  Minor (1)silodosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• 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.

• solriamfetol

  Monitor Closely (1)phenylephrine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• 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 (2)sufentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• tapentadol

  Monitor Closely (2)tapentadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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 (2)temazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  temazepam and doxylamine both increase sedation. Use Caution/Monitor.

• terazosin

  Minor (1)terazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• terbutaline

  Monitor Closely (2)terbutaline and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  terbutaline and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. 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 (3)thioridazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  thioridazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  Monitor Closely (2)doxylamine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tiagabine

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

• timolol

  Monitor Closely (1)timolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• tinidazole

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

• topiramate

  Monitor Closely (2)topiramate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  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.
  
  tramadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.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 (2)doxylamine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trazodone, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• triazolam

  Monitor Closely (2)triazolam and doxylamine both increase sedation. Use Caution/Monitor.
  
  triazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)doxylamine and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (3)doxylamine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  trifluoperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trimipramine

  Monitor Closely (2)trimipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• triprolidine

  Monitor Closely (2)triprolidine and doxylamine both increase sedation. Use Caution/Monitor.
  
  triprolidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. 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.

• warfarin

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

• xylometazoline

  Monitor Closely (3)phenylephrine and xylometazoline both decrease sedation. Use Caution/Monitor.
  
  doxylamine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenylephrine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• yohimbe

  Serious - Use Alternative (1)yohimbe, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• yohimbine

  Monitor Closely (2)yohimbine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• ziconotide

  Monitor Closely (2)ziconotide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)ziprasidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxylamine and ziprasidone both increase sedation. Use Caution/Monitor.

• 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.