diphenhydramine (Rx, OTC)

Brand and Other Names:Benadryl, Benadryl Allergy Dye-Free LiquiGels, more...Children's Benadryl Allergy, Children's Triaminic Thin Strips Allergy, Alka-Seltzer Plus Allergy, Nytol, PediaCare Children's Allergy, Simply Sleep, Sominex, QlearQuil Nighttime Allergy Relief, Tranquil Nighttime Sleep Aid, Unisom SleepGels, Unisom SleepMelts, ZzzQuil
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

oral liquid

  • 12.5mg/5mL (Benadryl Allergy Childrens, PediaCare Children’s Allergy, Allergy Relief Childrens)
  • 50mg/30mL (ZzzQuil)

elixir

  • 12.5 mg/5mL (Altaryl)

syrup

  • 12.5 mg/5mL (Altaryl, Quenalin, Silphen Cough)

tablet

  • 25mg (Benadryl, Nytol, Simply Sleep, Sominex, Simply Allergy, Tetra-Formula Nighttime Sleep)
  • 50mg (Aler-Dryl, Nytol Maximum Strength)

capsule

  • 25mg (Benadryl Allergy Dye-Free Allergy, Anti-Hist Allergy, Allergy Relief, Diphenhist, Geri-Dryl)
  • 50mg (Banophen, Pharbedryl)

tablet, chewable

  • 12.5mg (Benadryl Allergy Childrens)

tablet, dispersible

  • 25mg (Unisom SleepMelts)

strip

  • 12.5mg (Triaminnic Cough/Runny Nose)

injectable solution

  • 50mg/mL

Allergic Reaction

25-50 mg PO q6-8hr; not to exceed 300 mg/day

10-50 mg (no more than 100 mg) IV/IM q4-6hr; not to exceed 400 mg/day

Insomnia

50 mg PO 30 minutes before bedtime

Cough

25-50 mg PO q4hr PRN (syrup preferred); not to exceed 150 mg/day

Motion Sickness

Treatment or prophylaxis: 25-50 mg PO q6-8 hr

Alternatively, 10-50 mg/dose for treatment; may use up to 100 mg if needed; not to exceed 400 mg

Parkinsonism

25 mg PO q8hr initially, then 50 mg PO q6hr; not to exceed 300 mg/day

Alternatively, 10-50 mg IV at a rate not to exceed 25 mg/min; not to exceed 400 mg/day; may also administer 100 mg IM required

Dosage Forms & Strengths

oral solution

  • 12.5mg/5mL (Benadryl Allergy Childrens, PediaCare Children’s Allergy, Allergy Relief Childrens)
  • 50mg/30mL (ZzzQuil)

elixir

  • 12.5 mg/5mL (Altaryl)

syrup

  • 12.5 mg/5mL (Altaryl, Quenalin, Silphen Cough)

tablet

  • 25mg (Benadryl, Nytol, Simply Sleep, Sominex, Simply Allergy, Tetra-Formula Nighttime Sleep)
  • 50mg (Aler-Dryl, Nytol Maximum Strength)

capsule

  • 25mg (Benadryl Allergy Dye-Free Allergy, Anti-Hist, Allergy Relief, Diphenhist, Geri-Dryl)
  • 50mg (Banophen, Pharbedryl)

tablet, chewable

  • 12.5mg (Benadryl Allergy Childrens)

tablet, dispersible

  • 25mg (Unisom SleepMelts)

strip

  • 12.5mg (Triaminnic Cough/Runny Nose)

injectable solution

  • 50mg/mL

Allergic Reaction

2-6 years: 6.25 mg q4-6hr; not to exceed 37.5 mg/day

6-12 years: 12.5-25 mg PO q4-6hr; not to exceed 150 mg/day

>12 years: 25-50 mg PO q4-6hr; not to exceed 300 mg/day

Occasional Insomnia

< 12 years (off-label): 1 mg/kg; not to exceed 50 mg; 30 min before bedtime

>12 years: 50 mg PO 30 minutes before bedtime

Cough

<12 years: Safety and efficacy not established

>12 years: 25-50 mg PO q4-6hr; not to exceed 300 mg/day

Motion Sickness

Administer 30 min before motion

12.5-25 mg PO q6-8hr or 150 mg/m² ; not to exceed 300 mg/day

Allergic Reaction

25 mg PO/IV/IM q8-12hr; use only for emergency allergic reactions at smallest effective dose

Nonanticholinergic antihistamines should be considered first for treatment of allergic reaction (Beers criteria); use of diphenhydramine in acute treatment of severe allergic reaction may be appropriate

Dystonic Reaction

50 mg IV/IM; may be repeated in 20-30 minutes if necessary

Cough

25 mg PO q8-12hr; avoid in elderly if possible

Motion Sickness

25 mg PO/IV/IM q8-12hr

Dosing Modifications

Advanced age is associated with reduced clearance of drug and greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity; if used, consider lower doses

In patients with parkinsonism who are unable to tolerate more potent agents, use at lowest effective dose

Next:

Interactions

Interaction Checker

and diphenhydramine

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            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 (11)

            • 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. .

            • 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.

            • 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.

            • quinidine

              quinidine, diphenhydramine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of prolonged QTc interval.

            • sodium oxybate

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

            • thioridazine

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

            • tranylcypromine

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

            Monitor Closely (265)

            • aclidinium

              diphenhydramine and aclidinium both decrease cholinergic effects/transmission. 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • brompheniramine

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 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 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 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • isoproterenol

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

            • 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

              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.

            • 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.

            • 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.

            • 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.

            • midodrine

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

            • 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.

            • pilocarpine ophthalmic

              pilocarpine ophthalmic 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.

            • 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.

            • 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.

            • 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.

            • xylometazoline

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

            • yohimbine

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

            • ziconotide

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

            • ziprasidone

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

              diphenhydramine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              diphenhydramine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.

              ziprasidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • zotepine

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

              diphenhydramine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              diphenhydramine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.

            Minor (34)

            • 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.

            • brimonidine

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

            • chlorpromazine

              diphenhydramine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. 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.

            • dimenhydrinate

              dimenhydrinate increases toxicity of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • 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.

            • eucalyptus

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

            • 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.

            • 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.

            • loratadine

              diphenhydramine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 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.

            • 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.

            • 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.

            • risperidone

              diphenhydramine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 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.

            • tolterodine

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

            • 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.

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            Adverse Effects

            Frequency Not Defined

            Sedation

            Confusion

            Anticholinergic effects

            May decrease cognitive function in geriatric patients

            Xerostomia

            Dry nasal mucosa

            Pharyngeal dryness

            Thick bronchial sputum

            Agranulocytosis

            Hemolytic anemia

            Thrombocytopenia

            Convulsions

            Tachycardia

            Hypotension

            Nervousness

            Restlessness

            Blurred vision

            Palpitations

            Constipation

            Vertigo

            Menstrual irregularities

            Euphoria

            Anorexia

            Urinary retention

            Neuritis

            Diplopia

            Tinnitus

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            Warnings

            Contraindications

            Documented hypersensitivity

            Lower respiratory tract disease, such as acute asthma (controversial)

            Premature infants or neonates

            Nursing mothers

            Use as local anesthetic

            To make child <6 years sleep, when used for self-medication

            Cautions

            May cause CNS depression, which can impair driving or operating heavy machinery

            May potentiate effects of sedatives such as alcohol

            Use caution in patients with angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, thyroid dysfunction

            Elderly patients: Considered high-risk medication for this age group because it may increase risk of falls and has high incidence of anticholinergic effects; may exacerbate existing lower urinary tract conditions or benign prostatic hyperplasia; use in special situations may be appropriate; not recommended for treatment of insomnia, because tolerance develops and risk of anticholinergic effects increases

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            Pregnancy & Lactation

            Pregnancy category: B

            Lactation: Drug enters breast milk; contraindicated

            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.

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            Pharmacology

            Mechanism of Action

            Histamine H1-receptor antagonist of effector cells in respiratory tract, blood vessels, and GI smooth muscle

            Moderate to high anticholinergic and antiemetic properties

            Absorption

            Bioavailability: PO, 42-62% (drug is well absorbed but undergoes first-pass metabolism)

            Onset: 15-30 min

            Duration: ≤12 hr (histamine-induced flare suppression); ≤10 hr (histamine-induced wheal suppression)

            Peak serum time: 2 hr (PO)

            Distribution

            Protein bound: 98.5%

            Vd: 22 L/kg (Children); 17 L/kg (adults); 14 L/kg (elderly)

            Metabolism

            Metabolized by liver (first-pass)

            Elimination

            Half-life: 5 hr (children); 9 hr (adults); 13.5 hr (elderly)

            Excretion: Urine (50-75%), mainly as metabolites

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            Administration

            IV Incompatibilities

            Additive: Amobarbital, amphotericin B, dexamethasone, sodium phosphate with lorazepam and metoclopramide, iodipamide meglumine, phenytoin, phenobarbital, thiopental

            Syringe: Diatrizoate meglumine 52% and diatrizoate sodium 8%, diatrizoate sodium, haloperidol, iodipamide meglumine, ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%, pentobarbital, thiopental

            Y-site: Allopurinol, amphotericin B cholesteryl sulfate, cefepime, foscarnet, furosemide, phenytoin

            IV Administration

            pH: 5-6

            Infuse at rate no higher than 25 mg/min

            Check patency of IV and monitor for irritation

            Storage

            Store at room temperature of 15-30°C (59-86°F); protect from freezing and light

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.