Dosing & Uses
Dosage Forms & Strengths
acetaminophen/doxylamine/dextromethorphan
liquid
- (325mg/6.25mg/15mg)/15mL
- (500mg/6.25mg/15mg)/15mL
- (650mg/7.5mg/30mg)/30mL
- (650mg/12.5mg/30mg)/30mL
liquid capsule
- 325mg/6.25mg/15mg
Cough, Sore Throat, Rhinorrhea, Fever, Headache, Minor Aches & Pains
1-2 Tablespoons (15-30mL) PO q6hr; not to exceed a cumulative dose of acetaminophen 4 g/day and dextromethorphan 120 mg/day
2 capsules PO q6hr; not to exeed 8 capsules/day
Liquid formulation ingredients vary in dosage; follow specific brand instructions
Dosage Forms & Strengths
acetaminophen/doxylamine/dextromethorphan
liquid
- (500mg/6.25mg/15mg)/15mL
- (650mg/7.5mg/30mg)/30mL
- (650mg/12.5mg/30mg)/30mL
liquid capsule
- 325mg/6.25mg/15mg
Cough, Sore Throat, Rhinorrhea, Fever, Headache, Minor Aches & Pains
<12 Years Old
- Ask a pediatrician
>12 Years Old
- 2 Tablespoons (30mL) PO q6hr; not to exceed 120 mL/day
- 2 capsules PO q6hr; not to exeed 8 capsules/day
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (7)
- isocarboxazid
isocarboxazid and dextromethorphan both increase serotonin levels. Contraindicated.
- phenelzine
phenelzine and dextromethorphan both increase serotonin levels. Contraindicated.
- procarbazine
procarbazine and dextromethorphan both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.
- rasagiline
rasagiline and dextromethorphan both increase serotonin levels. Contraindicated. Risk of psychosis episodes or bizarre behavior.
- safinamide
dextromethorphan, safinamide. Other (see comment). Contraindicated. Comment: Coadministration of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior.
- selegiline
selegiline and dextromethorphan both increase serotonin levels. Contraindicated.
- tranylcypromine
tranylcypromine and dextromethorphan both increase serotonin levels. Contraindicated.
Serious - Use Alternative (44)
- amitriptyline
amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- amoxapine
amoxapine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- buspirone
buspirone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- calcium/magnesium/potassium/sodium oxybates
doxylamine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- citalopram
citalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- clomipramine
clomipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- desipramine
desipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- desvenlafaxine
dextromethorphan and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
- doxepin
doxepin and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- duloxetine
duloxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
duloxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. - escitalopram
escitalopram and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- fentanyl
fentanyl, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl intranasal
fentanyl intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transdermal
fentanyl transdermal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transmucosal
fentanyl transmucosal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fluoxetine
fluoxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
fluoxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. - fluvoxamine
fluvoxamine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- grapefruit
grapefruit will increase the level or effect of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- hydrocodone
hydrocodone, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- imipramine
imipramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- isocarboxazid
isocarboxazid increases effects of doxylamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
- lemborexant
lemborexant, doxylamine. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended.
- levomilnacipran
levomilnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- linezolid
linezolid and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
- lofepramine
lofepramine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- lonafarnib
acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
- lorcaserin
dextromethorphan and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.
- maprotiline
maprotiline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- memantine
memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.
- meperidine
dextromethorphan and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.
- methylene blue
methylene blue and doxylamine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first. - metoclopramide intranasal
doxylamine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
- milnacipran
milnacipran and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- nefazodone
nefazodone and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- nortriptyline
nortriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- olopatadine intranasal
doxylamine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- paroxetine
paroxetine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
paroxetine and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. - pexidartinib
acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.
- pretomanid
acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.
- protriptyline
protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- selegiline transdermal
selegiline transdermal and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
- selinexor
selinexor, doxylamine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
- sertraline
sertraline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.
Monitor Closely (244)
- 5-HTP
5-HTP and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- abiraterone
abiraterone increases levels of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
- acrivastine
acrivastine and doxylamine both increase sedation. Use Caution/Monitor.
- alfentanil
doxylamine and alfentanil both increase sedation. Use Caution/Monitor.
- almotriptan
almotriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- alprazolam
alprazolam and doxylamine both increase sedation. Use Caution/Monitor.
- amifampridine
doxylamine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
- amisulpride
amisulpride and doxylamine both increase sedation. Use Caution/Monitor.
- amitriptyline
doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.
- amobarbital
amobarbital and doxylamine both increase sedation. Use Caution/Monitor.
- amoxapine
doxylamine and amoxapine both increase sedation. Use Caution/Monitor.
- amphetamine
amphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .
- apalutamide
apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
- apomorphine
doxylamine and apomorphine both increase sedation. Use Caution/Monitor.
- aripiprazole
dextromethorphan, aripiprazole. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
doxylamine and aripiprazole both increase sedation. Use Caution/Monitor. - artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- asenapine
asenapine and doxylamine both increase sedation. Use Caution/Monitor.
- asenapine
dextromethorphan, asenapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- 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.
- 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 and doxylamine both increase sedation. Use Caution/Monitor.
- baclofen
doxylamine and baclofen both increase sedation. Use Caution/Monitor.
- belladonna and opium
doxylamine and belladonna and opium both increase sedation. Use Caution/Monitor.
- benperidol
doxylamine and benperidol both increase sedation. Use Caution/Monitor.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen and doxylamine both increase sedation. Use Caution/Monitor.
- benzphetamine
doxylamine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- brexanolone
brexanolone, doxylamine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- 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.
- brompheniramine
brompheniramine and doxylamine both increase sedation. Use Caution/Monitor.
- bupivacaine implant
acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.
- buprenorphine
doxylamine and buprenorphine both increase sedation. Use Caution/Monitor.
- buprenorphine buccal
doxylamine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
- buprenorphine subdermal implant
buprenorphine subdermal implant and doxylamine both increase sedation. Use Caution/Monitor.
- buprenorphine transdermal
buprenorphine transdermal 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.
buprenorphine, long-acting injection and doxylamine both increase sedation. Use Caution/Monitor. - bupropion
bupropion will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- busulfan
acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.
- butabarbital
butabarbital and doxylamine both increase sedation. Use Caution/Monitor.
- butalbital
butalbital and doxylamine both increase sedation. Use Caution/Monitor.
- butorphanol
doxylamine and butorphanol both increase sedation. Use Caution/Monitor.
- carbinoxamine
carbinoxamine and doxylamine both increase sedation. Use Caution/Monitor.
- cariprazine
dextromethorphan, cariprazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- carisoprodol
doxylamine and carisoprodol both increase sedation. Use Caution/Monitor.
- cenobamate
cenobamate, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and doxylamine both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.
- chlorpromazine
doxylamine and chlorpromazine both increase sedation. Use Caution/Monitor.
- chlorzoxazone
doxylamine and chlorzoxazone both increase sedation. Use Caution/Monitor.
- cinnarizine
cinnarizine and doxylamine both increase sedation. Use Caution/Monitor.
- clemastine
clemastine and doxylamine both increase sedation. Use Caution/Monitor.
- clobazam
doxylamine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
clobazam will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. - clomipramine
doxylamine and clomipramine both increase sedation. Use Caution/Monitor.
- clozapine
dextromethorphan, clozapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- clonazepam
clonazepam and doxylamine both increase sedation. Use Caution/Monitor.
- clonidine
clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.
- clorazepate
clorazepate and doxylamine both increase sedation. Use Caution/Monitor.
- clozapine
doxylamine and clozapine both increase sedation. Use Caution/Monitor.
- cocaine topical
cocaine topical and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- codeine
doxylamine and codeine both increase sedation. Use Caution/Monitor.
- cyclizine
cyclizine and doxylamine both increase sedation. Use Caution/Monitor.
- cyclobenzaprine
doxylamine and cyclobenzaprine both increase sedation. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and doxylamine both increase sedation. Use Caution/Monitor.
- dantrolene
doxylamine and dantrolene both increase sedation. Use Caution/Monitor.
- dapsone topical
acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .
- daridorexant
doxylamine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- desipramine
doxylamine and desipramine both increase sedation. Use Caution/Monitor.
- desvenlafaxine
desvenlafaxine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg
- deutetrabenazine
doxylamine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
dexfenfluramine and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
doxylamine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dexmedetomidine
dexmedetomidine and doxylamine both increase sedation. Use Caution/Monitor.
- dextroamphetamine
dextroamphetamine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. .
- dextroamphetamine transdermal
dextromethorphan, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).
dextroamphetamine transdermal, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when amphemtamines are coadministered with dextromethorphan. . - dextromoramide
doxylamine and dextromoramide both increase sedation. Use Caution/Monitor.
- diamorphine
doxylamine and diamorphine both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and doxylamine both increase sedation. Use Caution/Monitor.
- diazepam intranasal
diazepam intranasal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- difelikefalin
difelikefalin and doxylamine both increase sedation. Use Caution/Monitor.
- difenoxin hcl
doxylamine and difenoxin hcl both increase sedation. Use Caution/Monitor.
- dihydroergotamine
dextromethorphan and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
- dihydroergotamine intranasal
dextromethorphan and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.
- dimenhydrinate
dimenhydrinate and doxylamine both increase sedation. Use Caution/Monitor.
- diphenhydramine
diphenhydramine and doxylamine both increase sedation. Use Caution/Monitor.
- diphenoxylate hcl
doxylamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
- dipipanone
doxylamine and dipipanone both increase sedation. Use Caution/Monitor.
- dopexamine
doxylamine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
doxylamine and dosulepin both increase sedation. Use Caution/Monitor.
- doxepin
doxylamine and doxepin both increase sedation. Use Caution/Monitor.
- droperidol
doxylamine and droperidol both increase sedation. Use Caution/Monitor.
- eletriptan
eletriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- eltrombopag
eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
- ergotamine
dextromethorphan and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.
- esketamine intranasal
esketamine intranasal, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- estazolam
estazolam and doxylamine both increase sedation. Use Caution/Monitor.
- ethanol
doxylamine and ethanol both increase sedation. Use Caution/Monitor.
- etomidate
etomidate and doxylamine both increase sedation. Use Caution/Monitor.
- exenatide injectable solution
exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- exenatide injectable suspension
exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- fenfluramine
doxylamine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
fenfluramine, dextromethorphan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.
dextromethorphan and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely. - finerenone
acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.
- fluphenazine
dextromethorphan, fluphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- flibanserin
doxylamine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors. - fluphenazine
doxylamine and fluphenazine both increase sedation. Use Caution/Monitor.
- frovatriptan
frovatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- haloperidol
dextromethorphan, haloperidol. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- iloperidone
dextromethorphan, iloperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- imatinib
imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.
- flurazepam
flurazepam and doxylamine both increase sedation. Use Caution/Monitor.
- gabapentin
gabapentin, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- ganaxolone
doxylamine and ganaxolone both increase sedation. Use Caution/Monitor.
- gotu kola
gotu kola increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- haloperidol
doxylamine and haloperidol both increase sedation. Use Caution/Monitor.
- hawthorn
hawthorn increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hops
hops increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hyaluronidase
doxylamine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect. .
- hydromorphone
doxylamine and hydromorphone both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and doxylamine both increase sedation. Use Caution/Monitor.
- iloperidone
doxylamine and iloperidone both increase sedation. Use Caution/Monitor.
- imipramine
doxylamine and imipramine both increase sedation. Use Caution/Monitor.
- isavuconazonium sulfate
acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoniazid
dextromethorphan and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor. - L-tryptophan
dextromethorphan and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.
- ivacaftor
acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
- kava
kava increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- ketamine
ketamine and doxylamine both increase sedation. Use Caution/Monitor.
- ketotifen, ophthalmic
doxylamine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
- letermovir
letermovir increases levels of dextromethorphan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation. - levorphanol
doxylamine and levorphanol both increase sedation. Use Caution/Monitor.
- lithium
dextromethorphan and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
- lixisenatide (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.
- lofexidine
doxylamine and lofexidine both increase sedation. Use Caution/Monitor.
- lomitapide
acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- loprazolam
loprazolam and doxylamine both increase sedation. Use Caution/Monitor.
- lorazepam
lorazepam and doxylamine both increase sedation. Use Caution/Monitor.
- lormetazepam
lormetazepam and doxylamine both increase sedation. Use Caution/Monitor.
- loxapine
dextromethorphan, loxapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
doxylamine and loxapine both increase sedation. Use Caution/Monitor. - loxapine inhaled
doxylamine and loxapine inhaled both increase sedation. Use Caution/Monitor.
dextromethorphan, loxapine inhaled. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - lsd
dextromethorphan and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.
- lurasidone
lurasidone, doxylamine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
- lumefantrine
lumefantrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- lurasidone
dextromethorphan, lurasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- maprotiline
doxylamine and maprotiline both increase sedation. Use Caution/Monitor.
- marijuana
doxylamine and marijuana both increase sedation. Use Caution/Monitor.
- melatonin
doxylamine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
doxylamine and meperidine both increase sedation. Use Caution/Monitor.
- meprobamate
doxylamine and meprobamate both increase sedation. Use Caution/Monitor.
- metaxalone
doxylamine and metaxalone both increase sedation. Use Caution/Monitor.
- methadone
doxylamine and methadone both increase sedation. Use Caution/Monitor.
- methocarbamol
doxylamine and methocarbamol both increase sedation. Use Caution/Monitor.
- methylenedioxymethamphetamine
doxylamine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- midazolam
midazolam and doxylamine both increase sedation. Use Caution/Monitor.
- midazolam intranasal
midazolam intranasal, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation. - mipomersen
mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
- mirtazapine
doxylamine and mirtazapine both increase sedation. Use Caution/Monitor.
dextromethorphan and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. - molindone
dextromethorphan, molindone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- morphine
doxylamine and morphine both increase sedation. Use Caution/Monitor.
- morphine
dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- motherwort
doxylamine and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
doxylamine and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
doxylamine and nabilone both increase sedation. Use Caution/Monitor.
- nalbuphine
doxylamine and nalbuphine both increase sedation. Use Caution/Monitor.
- naratriptan
naratriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- nortriptyline
doxylamine and nortriptyline both increase sedation. Use Caution/Monitor.
- olanzapine
doxylamine and olanzapine both increase sedation. Use Caution/Monitor.
dextromethorphan, olanzapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - oliceridine
oliceridine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- paliperidone
dextromethorphan, paliperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- opium tincture
doxylamine and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
doxylamine and orphenadrine both increase sedation. Use Caution/Monitor.
- oxazepam
oxazepam and doxylamine both increase sedation. Use Caution/Monitor.
- oxycodone
doxylamine and oxycodone both increase sedation. Use Caution/Monitor.
- oxymorphone
doxylamine and oxymorphone both increase sedation. Use Caution/Monitor.
- paliperidone
doxylamine and paliperidone both increase sedation. Use Caution/Monitor.
- panobinostat
panobinostat will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.
- papaveretum
doxylamine and papaveretum both increase sedation. Use Caution/Monitor.
- papaverine
doxylamine and papaverine both increase sedation. Use Caution/Monitor.
- passion flower
passion flower increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- pazopanib
pazopanib increases levels of dextromethorphan by decreasing metabolism. Use Caution/Monitor.
- peginterferon alfa 2b
peginterferon alfa 2b, dextromethorphan. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
- pentazocine
dextromethorphan and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
doxylamine and pentazocine both increase sedation. Use Caution/Monitor. - pentobarbital
pentobarbital and doxylamine both increase sedation. Use Caution/Monitor.
- perphenazine
dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- perphenazine
doxylamine and perphenazine both increase sedation. Use Caution/Monitor.
- phenelzine
phenelzine increases effects of doxylamine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
- phenobarbital
phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.
- phenylephrine PO
doxylamine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
- pholcodine
doxylamine and pholcodine both increase sedation. Use Caution/Monitor.
- pimavanserin
dextromethorphan, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- pimozide
dextromethorphan, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
doxylamine and pimozide both increase sedation. Use Caution/Monitor. - pregabalin
pregabalin, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- quetiapine
dextromethorphan, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- primidone
primidone and doxylamine both increase sedation. Use Caution/Monitor.
- prochlorperazine
doxylamine and prochlorperazine both increase sedation. Use Caution/Monitor.
- promethazine
promethazine and doxylamine both increase sedation. Use Caution/Monitor.
- propofol
propofol and doxylamine both increase sedation. Use Caution/Monitor.
- propylhexedrine
doxylamine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- protriptyline
doxylamine and protriptyline both increase sedation. Use Caution/Monitor.
- quazepam
quazepam and doxylamine both increase sedation. Use Caution/Monitor.
- quetiapine
doxylamine and quetiapine both increase sedation. Use Caution/Monitor.
- quinidine
quinidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- ramelteon
doxylamine and ramelteon both increase sedation. Use Caution/Monitor.
- remimazolam
remimazolam, doxylamine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- risperidone
doxylamine and risperidone both increase sedation. Use Caution/Monitor.
dextromethorphan, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). - rizatriptan
rizatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- scullcap
doxylamine and scullcap both increase sedation. Use Caution/Monitor.
- rolapitant
rolapitant will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor for adverse reactions when unable to avoid coadministration with narrow therapeutic index CYP2D6 substrates.
- SAMe
dextromethorphan and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.
- secobarbital
secobarbital and doxylamine both increase sedation. Use Caution/Monitor.
- sevoflurane
sevoflurane and doxylamine both increase sedation. Use Caution/Monitor.
- shepherd's purse
doxylamine and shepherd's purse both increase sedation. Use Caution/Monitor.
- stiripentol
stiripentol, doxylamine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
- sufentanil
doxylamine and sufentanil both increase sedation. Use Caution/Monitor.
- sumatriptan
sumatriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- sumatriptan intranasal
sumatriptan intranasal and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
- tapentadol
doxylamine and tapentadol both increase sedation. Use Caution/Monitor.
- tazemetostat
acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- temazepam
temazepam and doxylamine both increase sedation. Use Caution/Monitor.
- tetracaine
tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.
- thioridazine
doxylamine and thioridazine both increase sedation. Use Caution/Monitor.
- thiothixene
dextromethorphan, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
doxylamine and thiothixene both increase sedation. Use Caution/Monitor. - tinidazole
acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tramadol
dextromethorphan and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
- topiramate
doxylamine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
doxylamine and tramadol both increase sedation. Use Caution/Monitor.
- trazodone
doxylamine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
triazolam and doxylamine both increase sedation. Use Caution/Monitor.
- triclofos
doxylamine and triclofos both increase sedation. Use Caution/Monitor.
- trifluoperazine
dextromethorphan, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
doxylamine and trifluoperazine both increase sedation. Use Caution/Monitor. - trimipramine
doxylamine and trimipramine both increase sedation. Use Caution/Monitor.
- ziprasidone
dextromethorphan, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
- triprolidine
triprolidine and doxylamine both increase sedation. Use Caution/Monitor.
- valerian
valerian increases effects of doxylamine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- warfarin
acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.
- xylometazoline
doxylamine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- zolmitriptan
zolmitriptan and dextromethorphan both increase serotonin levels. Modify Therapy/Monitor Closely.
Minor (74)
- acetazolamide
acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- albiglutide
albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- amiodarone
amiodarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- antithrombin alfa
acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.
- antithrombin III
acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.
- argatroban
acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.
- asenapine
asenapine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ashwagandha
ashwagandha increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- bemiparin
acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.
- bivalirudin
acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.
- brimonidine
brimonidine increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- carbamazepine
carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- celecoxib
celecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- chloroquine
chloroquine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- cholestyramine
cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- cimetidine
cimetidine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- clonazepam
clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- colestipol
colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- dalteparin
acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.
- darifenacin
darifenacin will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- diazepam
diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- diphenhydramine
diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- disulfiram
disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- dronedarone
dronedarone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- enoxaparin
acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.
- ethanol
ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown. - ethosuximide
ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- eucalyptus
doxylamine and eucalyptus both increase sedation. Minor/Significance Unknown.
- felbamate
felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- fondaparinux
acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.
- fosphenytoin
fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- green tea
green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).
- haloperidol
haloperidol will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- heparin
acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.
- imatinib
imatinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- isoniazid
isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.
- lacosamide
lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- lamotrigine
lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- levetiracetam
levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- liraglutide
liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- lorazepam
lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- maraviroc
maraviroc will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- marijuana
marijuana will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- methsuximide
methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- metoclopramide
metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- metronidazole
metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- nettle
nettle increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.
- nilotinib
nilotinib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- oxcarbazepine
oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- oxybutynin
oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin topical
oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- oxybutynin transdermal
oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- parecoxib
parecoxib will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- perphenazine
perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- phenindione
acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.
- phenobarbital
phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- phenytoin
phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- primidone
primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- propafenone
propafenone will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- protamine
acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- quinacrine
quinacrine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- rifabutin
rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- rifampin
rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- ritonavir
ritonavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- rufinamide
rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- ruxolitinib
acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
doxylamine and sage both increase sedation. Minor/Significance Unknown.
- Siberian ginseng
Siberian ginseng increases effects of doxylamine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- sertraline
sertraline will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- thioridazine
thioridazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- tiagabine
tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- tipranavir
tipranavir will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
Adverse Effects
Frequency Not Defined
Angioedema
Laryngeal edema
Dizziness
Drowsiness
Pruritic maculopapular rash
Urticaria
Dry mouth, throat, and nose
Agranulocytosis
Leukopenia
Neutropenia
Pancytopenia
Thrombocytopenia
Thrombocytopenic purpura
Hepatotoxicity
Thickening of mucus in nose or throat
Anaphylactoid reaction
Warnings
Contraindications
Coadministration with other acetaminophen-containing drugs would exceed 4 g/day acetaminophen
Within 14 days of taking a MAO inhibitor, including linezolid, rasagiline, isocarboxazid, selegiline, phenelzine, tranylcypromine
<12 years of age
Hypersensitivity to acetaminophen, doxylamine, dextromethorphan, or excipients
Use in pediatric sedation
Cautions
Acetaminophen hepatotoxicity possible in chronic alcoholics following various dose levels
Severe or recurrent pain or high or continued fever may indicate a serious illness
Acetaminophen contained in many OTC products and combined use with these products may result in toxicity due to cumulative doses exceeding recommended maximum dose
Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash
Doxylamine may exacerbate angle closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; xerostomia may occur
Do not take dextromethorphan for persistent or chronic cough associated with smoking, asthma, or emphysema, or if it is accompanied by excessive phlegm unless directed by a healthcare provider; dextromethorphan may slow the breathing
May cause CNS depression impairing physical or mental abilities; caution patients about performing hazardous tasks or operating heavy machinery, requiring mental alertness
Use caution in patients with diabetes mellitus, cardiovascular disease (eg, hypertension, ischemic heart disease), increased intraocular pressure or angle-closure glaucoma, prostatic hyperplasia, urinary obstruction, GU obstruction, asthma or respiratory disease, thyroid dysfunction, or G6PD deficiency
Pregnancy & Lactation
Pregnancy
Not known whether this medication will harm an unborn baby; do not use cough and cold medicine without a doctor's advice if you are pregnant.
Lactation
This medication may pass into breast milk and may harm a nursing baby; antihistamines may also slow breast milk production; do not use cough and cold medicine without a doctor's advice if you are breast-feeding a baby
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Acetaminophen: Blocks pain impulse generation peripherally and may inhibit prostaglandin generation in CNS; reduces fever by inhibiting hypothalamic heat-regulating center
Doxylamine: Competitively blocks histamine from binding to H1 receptors; significant antimuscarinic activity and penetrates CNS, which causes pronounced tendency to induce sedation
Dextromethorphan: Cough suppressant that acts centrally on cough center in medulla