Dosing & Uses
Dosage Forms & Strengths
acetaminophen/diphenhydramine/dextromethorphan
oral solution
- (325mg/12.5mg/10mg)/5mL
Cold & Flu
Indicated for relief of cold and flu symptoms
10 mL PO q4hr PRN; not to exceed 6 doses/24 hr
Dosage Forms & Strengths
acetaminophen/diphenhydramine/dextromethorphan
oral solution
- (325mg/12.5mg/10mg)/5mL
Cold & Flu
Indicated for relief of cold and flu symptoms
<6 years: Safety and efficacy not established
6-12 years: 5 mL PO q4hr PRN; not to exceed 6 doses/24 hr
>12 years: As adults; 10 mL PO q4hr PRN; not to exceed 6 doses/24 hr
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (1)
- eliglustat
diphenhydramine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.
Serious - Use Alternative (12)
- calcium/magnesium/potassium/sodium oxybates
diphenhydramine, 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.
- eluxadoline
diphenhydramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.
- isocarboxazid
isocarboxazid increases effects of diphenhydramine 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. .
- 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.
- mefloquine
mefloquine increases toxicity of diphenhydramine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
- metoclopramide intranasal
diphenhydramine, 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.
- olopatadine intranasal
diphenhydramine 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.
- pitolisant
diphenhydramine decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.
- pramlintide
pramlintide, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.
- 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.
- quinidine
quinidine, diphenhydramine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of prolonged QTc interval.
Monitor Closely (297)
- aclidinium
diphenhydramine and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- acrivastine
acrivastine and diphenhydramine both increase sedation. Use Caution/Monitor.
- albuterol
diphenhydramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
diphenhydramine and alfentanil both increase sedation. Use Caution/Monitor.
- alprazolam
diphenhydramine and alprazolam both increase sedation. Use Caution/Monitor.
- amantadine
diphenhydramine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.
- amifampridine
diphenhydramine 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 diphenhydramine both increase sedation. Use Caution/Monitor.
- amitriptyline
diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor. - amobarbital
diphenhydramine and amobarbital both increase sedation. Use Caution/Monitor.
- amoxapine
diphenhydramine and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and amoxapine both increase sedation. Use Caution/Monitor. - anticholinergic/sedative combos
anticholinergic/sedative combos and diphenhydramine both decrease cholinergic effects/transmission. 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
diphenhydramine and apomorphine both increase sedation. Use Caution/Monitor.
- arformoterol
diphenhydramine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- aripiprazole
diphenhydramine and aripiprazole both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.
aripiprazole increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - armodafinil
diphenhydramine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- asenapine
asenapine and diphenhydramine both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and diphenhydramine 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
diphenhydramine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- atracurium
atracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- atropine
atropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- atropine IV/IM
atropine IV/IM and diphenhydramine both decrease cholinergic effects/transmission. 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 diphenhydramine 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 diphenhydramine both increase sedation. Use Caution/Monitor.
- baclofen
diphenhydramine and baclofen both increase sedation. Use Caution/Monitor.
- belladonna alkaloids
belladonna alkaloids and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- belladonna and opium
diphenhydramine and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and belladonna and opium both increase sedation. Use Caution/Monitor. - benperidol
diphenhydramine and benperidol both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.
benperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - benzhydrocodone/acetaminophen
diphenhydramine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.
benzhydrocodone/acetaminophen and diphenhydramine both increase sedation. Use Caution/Monitor. - benzphetamine
diphenhydramine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- benztropine
benztropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.
- bethanechol
bethanechol increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- brexanolone
brexanolone, diphenhydramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
brexpiprazole and diphenhydramine both increase sedation. Use Caution/Monitor. - brimonidine
brimonidine and diphenhydramine both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and diphenhydramine both increase sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine and diphenhydramine 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
diphenhydramine and buprenorphine both increase sedation. Use Caution/Monitor.
- buprenorphine buccal
diphenhydramine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
- buprenorphine subdermal implant
buprenorphine subdermal implant and diphenhydramine both increase sedation. Use Caution/Monitor.
- buprenorphine transdermal
buprenorphine transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and diphenhydramine both increase sedation. 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
diphenhydramine and butabarbital both increase sedation. Use Caution/Monitor.
- butalbital
diphenhydramine and butalbital both increase sedation. Use Caution/Monitor.
- butorphanol
diphenhydramine and butorphanol both increase sedation. Use Caution/Monitor.
- caffeine
diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- carbachol
carbachol increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- carbinoxamine
carbinoxamine and diphenhydramine both increase sedation. Use Caution/Monitor.
- carisoprodol
diphenhydramine and carisoprodol both increase sedation. Use Caution/Monitor.
- carvedilol
diphenhydramine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- cenobamate
cenobamate, diphenhydramine. Either increases effects of the other by sedation. Use Caution/Monitor.
- cevimeline
cevimeline increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chloral hydrate
diphenhydramine and chloral hydrate both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
diphenhydramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor.
- chlorpromazine
diphenhydramine and chlorpromazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.
chlorpromazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - chlorzoxazone
diphenhydramine and chlorzoxazone both increase sedation. Use Caution/Monitor.
- cinnarizine
cinnarizine and diphenhydramine both increase sedation. Use Caution/Monitor.
- cisatracurium
cisatracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- clemastine
clemastine and diphenhydramine both increase sedation. Use Caution/Monitor.
- clobazam
diphenhydramine, 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
diphenhydramine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and clomipramine both increase sedation. Use Caution/Monitor. - clonazepam
diphenhydramine and clonazepam both increase sedation. Use Caution/Monitor.
- clorazepate
diphenhydramine and clorazepate both increase sedation. Use Caution/Monitor.
- clozapine
diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
clozapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - codeine
diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
diphenhydramine and codeine both increase sedation. Use Caution/Monitor. - cyclizine
cyclizine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
cyclizine and diphenhydramine both increase sedation. Use Caution/Monitor. - cyclobenzaprine
cyclobenzaprine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and cyclobenzaprine both increase sedation. Use Caution/Monitor. - cyproheptadine
cyproheptadine and diphenhydramine both increase sedation. Use Caution/Monitor.
- dantrolene
diphenhydramine 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
diphenhydramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
- darifenacin
darifenacin and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- desflurane
desflurane and diphenhydramine both increase sedation. Use Caution/Monitor.
- desipramine
diphenhydramine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and desipramine both increase sedation. Use Caution/Monitor. - deutetrabenazine
diphenhydramine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
diphenhydramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexmedetomidine
diphenhydramine and dexmedetomidine both increase sedation. Use Caution/Monitor.
- dexmethylphenidate
diphenhydramine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextroamphetamine
diphenhydramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextromoramide
diphenhydramine and dextromoramide both increase sedation. Use Caution/Monitor.
- diamorphine
diphenhydramine and diamorphine both increase sedation. Use Caution/Monitor.
- diazepam
diphenhydramine and diazepam both increase sedation. Use Caution/Monitor.
- diazepam intranasal
diazepam intranasal, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.
- dicyclomine
dicyclomine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- diethylpropion
diphenhydramine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and diphenhydramine both increase sedation. Use Caution/Monitor.
- difenoxin hcl
diphenhydramine and difenoxin hcl both increase sedation. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate and diphenhydramine both increase sedation. Use Caution/Monitor.
- diphenoxylate hcl
diphenhydramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
- dipipanone
diphenhydramine and dipipanone both increase sedation. Use Caution/Monitor.
- dobutamine
diphenhydramine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- donepezil
donepezil increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- donepezil transdermal
donepezil transdermal, diphenhydramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.
- dopamine
diphenhydramine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
diphenhydramine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
diphenhydramine and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and dosulepin both increase sedation. Use Caution/Monitor. - doxepin
diphenhydramine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and doxepin both increase sedation. Use Caution/Monitor. - doxylamine
diphenhydramine and doxylamine both increase sedation. Use Caution/Monitor.
- droperidol
diphenhydramine and droperidol both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.
droperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - duloxetine
diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- echothiophate iodide
echothiophate iodide increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- eltrombopag
eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
- ephedrine
diphenhydramine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine
diphenhydramine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine racemic
diphenhydramine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, diphenhydramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- estazolam
diphenhydramine and estazolam both increase sedation. Use Caution/Monitor.
- ethanol
diphenhydramine and ethanol both increase sedation. Use Caution/Monitor.
- etomidate
etomidate and diphenhydramine 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
diphenhydramine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- fentanyl
fentanyl, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
fentanyl and diphenhydramine both increase sedation. Use Caution/Monitor. - fentanyl intranasal
fentanyl intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
fentanyl intranasal and diphenhydramine both increase sedation. Use Caution/Monitor. - fentanyl iontophoretic transdermal system
fentanyl iontophoretic transdermal system and diphenhydramine both increase sedation. Use Caution/Monitor.
- fentanyl transdermal
fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor. - fentanyl transmucosal
fentanyl transmucosal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
- fesoterodine
diphenhydramine and fesoterodine both decrease cholinergic effects/transmission. 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.
- flavoxate
diphenhydramine and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.
- flecainide
diphenhydramine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- flibanserin
diphenhydramine 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
diphenhydramine and fluphenazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
fluphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - 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
diphenhydramine and flurazepam both increase sedation. Use Caution/Monitor.
- formoterol
diphenhydramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- gabapentin
gabapentin, diphenhydramine. 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, diphenhydramine. 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.
- galantamine
galantamine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ganaxolone
diphenhydramine and ganaxolone both increase sedation. Use Caution/Monitor.
- glycopyrrolate
diphenhydramine and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.
- glycopyrrolate inhaled
diphenhydramine and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.
- glycopyrronium tosylate topical
glycopyrronium tosylate topical, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.
- gotu kola
gotu kola increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- haloperidol
diphenhydramine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and haloperidol both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.
haloperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - hawthorn
hawthorn increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- henbane
diphenhydramine and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.
- homatropine
diphenhydramine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- hops
hops increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- huperzine A
huperzine A increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- hyaluronidase
diphenhydramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.
- hydrocodone
diphenhydramine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.
- hydromorphone
diphenhydramine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and hydromorphone both increase sedation. Use Caution/Monitor. - hydroxyzine
diphenhydramine and hydroxyzine both increase sedation. Use Caution/Monitor.
- hyoscyamine
diphenhydramine and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- hyoscyamine spray
diphenhydramine and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.
- iloperidone
diphenhydramine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and iloperidone both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.
iloperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - imipramine
diphenhydramine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and imipramine both increase sedation. Use Caution/Monitor. - ipratropium
diphenhydramine and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.
- 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.
- isoproterenol
diphenhydramine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. 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 diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- ketamine
ketamine and diphenhydramine both increase sedation. Use Caution/Monitor.
- ketotifen, ophthalmic
diphenhydramine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, diphenhydramine. 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.
lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. - levalbuterol
diphenhydramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. 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. - levodopa
diphenhydramine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .
- levorphanol
diphenhydramine and levorphanol both increase sedation. Use Caution/Monitor.
- lisdexamfetamine
diphenhydramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. 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
diphenhydramine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and lofepramine both increase sedation. Use Caution/Monitor. - lofexidine
diphenhydramine 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
diphenhydramine and loprazolam both increase sedation. Use Caution/Monitor.
- lorazepam
diphenhydramine and lorazepam both increase sedation. Use Caution/Monitor.
- lormetazepam
diphenhydramine and lormetazepam both increase sedation. Use Caution/Monitor.
- loxapine
diphenhydramine and loxapine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.
loxapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - loxapine inhaled
loxapine inhaled increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
diphenhydramine and loxapine inhaled both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor. - lurasidone
lurasidone, diphenhydramine. 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
diphenhydramine and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and maprotiline both increase sedation. Use Caution/Monitor. - marijuana
diphenhydramine and marijuana both increase sedation. Use Caution/Monitor.
- meclizine
diphenhydramine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- melatonin
diphenhydramine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
diphenhydramine and meperidine both increase sedation. Use Caution/Monitor.
- meprobamate
diphenhydramine and meprobamate both increase sedation. Use Caution/Monitor.
- metaproterenol
diphenhydramine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaxalone
diphenhydramine and metaxalone both increase sedation. Use Caution/Monitor.
- methadone
diphenhydramine and methadone both increase sedation. Use Caution/Monitor.
- methamphetamine
diphenhydramine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - methocarbamol
diphenhydramine and methocarbamol both increase sedation. Use Caution/Monitor.
- methscopolamine
diphenhydramine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- methylenedioxymethamphetamine
diphenhydramine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metoprolol
diphenhydramine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- mexiletine
diphenhydramine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- midazolam
diphenhydramine and midazolam both increase sedation. Use Caution/Monitor.
- midazolam intranasal
midazolam intranasal, diphenhydramine. 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
diphenhydramine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. 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
diphenhydramine and mirtazapine both increase sedation. Use Caution/Monitor.
- modafinil
diphenhydramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- morphine
diphenhydramine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and morphine both increase sedation. Use Caution/Monitor. - motherwort
diphenhydramine and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
diphenhydramine and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
diphenhydramine and nabilone both increase sedation. Use Caution/Monitor.
- nalbuphine
diphenhydramine and nalbuphine both increase sedation. Use Caution/Monitor.
- nebivolol
diphenhydramine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- neostigmine
neostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- norepinephrine
diphenhydramine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nortriptyline
diphenhydramine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and nortriptyline both increase sedation. Use Caution/Monitor. - olanzapine
diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
olanzapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - oliceridine
diphenhydramine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
- onabotulinumtoxinA
onabotulinumtoxinA and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- opium tincture
diphenhydramine and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
diphenhydramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and orphenadrine both increase sedation. Use Caution/Monitor. - ospemifene
diphenhydramine, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.
- oxazepam
diphenhydramine and oxazepam both increase sedation. Use Caution/Monitor.
- oxybutynin
diphenhydramine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.
- oxybutynin topical
diphenhydramine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.
- oxybutynin transdermal
diphenhydramine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.
- oxycodone
diphenhydramine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and oxycodone both increase sedation. Use Caution/Monitor. - oxymorphone
diphenhydramine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and oxymorphone both increase sedation. Use Caution/Monitor. - paliperidone
diphenhydramine and paliperidone both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
paliperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - pancuronium
diphenhydramine and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- papaveretum
diphenhydramine and papaveretum both increase sedation. Use Caution/Monitor.
- papaverine
diphenhydramine and papaverine both increase sedation. Use Caution/Monitor.
- passion flower
passion flower increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- pentazocine
diphenhydramine and pentazocine both increase sedation. Use Caution/Monitor.
- pentobarbital
diphenhydramine and pentobarbital both increase sedation. Use Caution/Monitor.
- perampanel
perampanel and diphenhydramine both increase sedation. Use Caution/Monitor.
- perphenazine
diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - phendimetrazine
diphenhydramine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenelzine
phenelzine increases effects of diphenhydramine 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
diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.
- phentermine
diphenhydramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenylephrine
diphenhydramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- phenylephrine PO
diphenhydramine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
- pholcodine
diphenhydramine and pholcodine both increase sedation. Use Caution/Monitor.
- physostigmine
physostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pilocarpine
pilocarpine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pimozide
diphenhydramine and pimozide both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.
pimozide increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - pirbuterol
diphenhydramine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pralidoxime
diphenhydramine and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.
- pregabalin
pregabalin, diphenhydramine. 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.
- primidone
diphenhydramine and primidone both increase sedation. Use Caution/Monitor.
- prochlorperazine
diphenhydramine and prochlorperazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.
prochlorperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - promethazine
diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - propafenone
diphenhydramine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- propantheline
diphenhydramine and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.
- propofol
propofol and diphenhydramine both increase sedation. Use Caution/Monitor.
- propranolol
diphenhydramine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- propylhexedrine
diphenhydramine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- protriptyline
diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor. - pyridostigmine
pyridostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- quazepam
diphenhydramine and quazepam both increase sedation. Use Caution/Monitor.
- quetiapine
diphenhydramine and quetiapine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
quetiapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - ramelteon
diphenhydramine and ramelteon both increase sedation. Use Caution/Monitor.
- rapacuronium
diphenhydramine and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- risperidone
diphenhydramine and risperidone both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
risperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - rocuronium
diphenhydramine and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- salmeterol
diphenhydramine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- scopolamine
diphenhydramine and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- scullcap
diphenhydramine and scullcap both increase sedation. Use Caution/Monitor.
- secobarbital
diphenhydramine and secobarbital both increase sedation. Use Caution/Monitor.
- sevoflurane
sevoflurane and diphenhydramine both increase sedation. Use Caution/Monitor.
- shepherd's purse
diphenhydramine and shepherd's purse both increase sedation. Use Caution/Monitor.
- solifenacin
diphenhydramine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.
- stiripentol
stiripentol, diphenhydramine. 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.
- succinylcholine
succinylcholine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- sufentanil
diphenhydramine and sufentanil both increase sedation. Use Caution/Monitor.
- tamoxifen
diphenhydramine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.
- tamsulosin
diphenhydramine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- tapentadol
diphenhydramine 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
diphenhydramine and temazepam both increase sedation. Use Caution/Monitor.
- terbutaline
diphenhydramine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. 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
diphenhydramine and thioridazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.
thioridazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - thiothixene
diphenhydramine and thiothixene both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
thiothixene increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - timolol
diphenhydramine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- tinidazole
acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tiotropium
diphenhydramine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- tolterodine
diphenhydramine and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.
- topiramate
diphenhydramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
diphenhydramine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
diphenhydramine and tramadol both increase sedation. Use Caution/Monitor.
diphenhydramine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite. - trazodone
diphenhydramine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
diphenhydramine and triazolam both increase sedation. Use Caution/Monitor.
- triclofos
diphenhydramine and triclofos both increase sedation. Use Caution/Monitor.
- trifluoperazine
diphenhydramine and trifluoperazine both increase sedation. Use Caution/Monitor.
diphenhydramine decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
diphenhydramine decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.
trifluoperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. - trihexyphenidyl
diphenhydramine and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.
- trimipramine
diphenhydramine and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
diphenhydramine and trimipramine both increase sedation. Use Caution/Monitor. - triprolidine
diphenhydramine and triprolidine both increase sedation. Use Caution/Monitor.
- trospium chloride
diphenhydramine and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.
- valerian
valerian increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- vecuronium
diphenhydramine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.
- warfarin
acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.
- xylometazoline
diphenhydramine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
Minor (82)
- 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.
- 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.
- aripiprazole
diphenhydramine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- ashwagandha
ashwagandha increases effects of diphenhydramine 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 diphenhydramine 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.
- chlorpromazine
diphenhydramine will increase the level or effect of chlorpromazine 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.
- 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.
- desipramine
diphenhydramine and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.
desipramine and diphenhydramine both decrease cholinergic effects/transmission. Minor/Significance Unknown. - dexfenfluramine
diphenhydramine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- dextroamphetamine
diphenhydramine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- dextromethorphan
diphenhydramine 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.
- dimenhydrinate
dimenhydrinate increases toxicity of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
- disulfiram
disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- donepezil
diphenhydramine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
donepezil decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown. - doxepin
diphenhydramine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- encainide
diphenhydramine will increase the level or effect of encainide 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
diphenhydramine 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.
- fesoterodine
diphenhydramine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- fluoxetine
diphenhydramine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- fluphenazine
diphenhydramine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- 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.
- galantamine
diphenhydramine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
galantamine decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown. - 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.
- loratadine
diphenhydramine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. 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.
- nettle
nettle increases effects of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.
- nitazoxanide
nitazoxanide, diphenhydramine. Either increases levels of the other by Mechanism: plasma protein binding competition. 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.
- oxycodone
diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.
- paroxetine
diphenhydramine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- perhexiline
diphenhydramine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- perphenazine
diphenhydramine will increase the level or effect of perphenazine 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.
- prochlorperazine
diphenhydramine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- promazine
diphenhydramine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- promethazine
diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- 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.
- risperidone
diphenhydramine will increase the level or effect of risperidone 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
diphenhydramine and sage both increase sedation. Minor/Significance Unknown.
- Siberian ginseng
Siberian ginseng increases effects of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- tiagabine
tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- tolterodine
diphenhydramine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- topiramate
topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- trazodone
diphenhydramine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.
- trifluoperazine
diphenhydramine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- tropisetron
diphenhydramine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- valproic acid
valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
Adverse Effects
Frequency Not Defined
Common
- Nausea/Vomiting
- Thick sputum
- Constipation
- Drowsiness
- Dizziness
- Sedation
- Blurred vision
- Nystagmus
Less Common
- Angioedema, Laryngeal edema
- Disorientation, Dizziness, Sedation, Confusion, Decreased cognitive function in elderly
- Pruritic maculopapular rash, Rash, Stevens-Johnson syndrome, Toxic epidermal necrolysis, Urticaria
- Agranulocytosis, Leukopenia, Neutropenia, Pancytopenia, Thrombocytopenia
- Thrombocytopenic purpura
- Hepatotoxicity, Liver failure Gastrointestinal hemorrhage, Nephrotoxicity, Pneumonitis, Anaphylactoid reactions
- Anticholinergic effects, Xerostomia, Dry nasal mucosa, Pharyngeal dryness
Warnings
Contraindications
Hypersensitivity
Hepatitis or hepatic/renal dysfunction, alcoholism
Repeated administration in patients with anemia or cardiac, pulmonary, or renal disease
Use within 14 days of MAO inhibitor therapy
Lower respiratory disease, eg, asthma (controversial)
Premature newborns and neonates
Nursing women
Cautions
Acetaminophen is found in many other dosage forms and products, check label carefully to avoid overdose
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
Risk of hepatotoxicity is higher in alcoholics or with use of more than one acetaminophen-containing product
G6PD deficiency
Phenylketonuria (phenylalanine in orange flavoring)
Driving or operating machinery
Avoid alcohol
Caution in narrow angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, or bladder neck obstruction
Pregnancy & Lactation
Pregnancy Category
Acetaminophen: Class B
Diphenhydramine: Class B
Dextromethorphan: Class C
Lactation
Acetaminophen: Excreted in breast milk; compatible with breastfeeding
Diphenhydramine: Enters breast milk/contraindicated
Dextromethorphan: Unknown if excreted in breast milk, use caution
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 the generation of prostaglandin in the CNS; reduces fever by inhibiting the hypothalamic heat-regulating center
Diphenhydramine: competitively blocks histamine from binding to H1 receptors; significant antimuscarinic activity and penetrates CNS, which causes pronounced tendency to induce sedation
Dextromethorphan is a cough suppressant that acts centrally on the cough center in the medulla
Pharmacokinetics
Acetaminophen
- Peak plasma time: 10-60 min (PO immediate release); 60-120 min (PO extended release); 6 hr (PO 500 mg tablet); 8 hr (PO 650 mg extended release tablet)
- Vd: 1 L/kg
- Protein binding: 10-25%
- Metabolism: Liver (microsomal enzyme systems); conjugation (glucuronic acid)
- Half-life: 1.25-3hr
- Excretion: Urine
Diphenhydramine
- Bioavailability: 42-62% (PO)
- Onset: 15-30 min
- Duration: 4-6 hr
- Peak plasma time: 2 hr (PO)
- Protein bound: 98.5%
- Vd: 22 L/kg (children); 17 L/kg (adults); 14 L/kg (Elderly)
- Half-life: 5 hr (children); 9 hr (adults); 13.5 hr (elderly)
- Excretion: Urine (50-75%)
Dextromethorphan
- Onset: 15-30 min
- Duration: 3-6 hr
- Metabolism: Hepatic P450 enzyme CYP2D6
- Excretion: Urine
- Half-life: 2-4 hr (extensive metabolizers); 24 hr (poor metabolizers)
- Peak plasma time: 2-3 hr