diphenhydramine (Rx, OTC)

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

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

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.

• aclidinium

  Monitor Closely (1)diphenhydramine and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• albuterol

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

• alfentanil

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

• alprazolam

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

• amantadine

  Monitor Closely (1)diphenhydramine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

• amifampridine

  Monitor Closely (1)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

  Monitor Closely (2)diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

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

• amoxapine

  Monitor Closely (2)diphenhydramine and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and amoxapine both increase sedation. Use Caution/Monitor.

• anticholinergic/sedative combos

  Monitor Closely (1)anticholinergic/sedative combos and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• apomorphine

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

• arformoterol

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

• aripiprazole

  Monitor Closely (4)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.
  
  diphenhydramine and aripiprazole both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

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

• ashwagandha

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

• atomoxetine

  Monitor Closely (1)diphenhydramine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• atracurium

  Monitor Closely (1)atracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  Monitor Closely (1)atropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine IV/IM

  Monitor Closely (1)atropine IV/IM and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• azelastine

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

• baclofen

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

• belladonna alkaloids

  Monitor Closely (1)belladonna alkaloids and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (2)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

  Monitor Closely (4)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.
  
  diphenhydramine and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)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

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

• benztropine

  Monitor Closely (1)benztropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

• bethanechol

  Monitor Closely (1)bethanechol increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• brexanolone

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

• brexpiprazole

  Monitor Closely (1)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.

• brimonidine

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

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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.

• carbachol

  Monitor Closely (1)carbachol increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

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

• carisoprodol

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

• carvedilol

  Monitor Closely (1)diphenhydramine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• cenobamate

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

• cevimeline

  Monitor Closely (1)cevimeline increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloral hydrate

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

• chlordiazepoxide

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

• chlorpheniramine

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

• chlorpromazine

  Monitor Closely (4)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.
  
  diphenhydramine and chlorpromazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorzoxazone

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

• cinnarizine

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

• cisatracurium

  Monitor Closely (1)cisatracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• clemastine

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

• clobazam

  Monitor Closely (1)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

  Monitor Closely (3)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

  Monitor Closely (1)diphenhydramine and clonazepam both increase sedation. Use Caution/Monitor.

• clorazepate

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

• clozapine

  Monitor Closely (4)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.
  
  diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.

• codeine

  Monitor Closely (2)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

  Monitor Closely (2)cyclizine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and diphenhydramine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)cyclobenzaprine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyproheptadine

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

• dantrolene

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

• darifenacin

  Monitor Closely (1)darifenacin and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• desflurane

  Monitor Closely (1)desflurane and diphenhydramine both increase sedation. Use Caution/Monitor.

• desipramine

  Monitor Closely (2)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.Minor (2)diphenhydramine and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  desipramine and diphenhydramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexfenfluramine

  Monitor Closely (1)diphenhydramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

  Monitor Closely (1)diphenhydramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromethorphan

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

• dextromoramide

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

• diamorphine

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

• diazepam

  Monitor Closely (1)diphenhydramine and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)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

  Monitor Closely (1)dicyclomine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

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

• difenoxin hcl

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

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and diphenhydramine both increase sedation. Use Caution/Monitor.Minor (1)dimenhydrinate increases toxicity of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

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

• donepezil

  Monitor Closely (1)donepezil increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)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.

• dopamine

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

• dopexamine

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

• dosulepin

  Monitor Closely (2)diphenhydramine and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  Monitor Closely (2)diphenhydramine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and doxepin both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• doxylamine

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

• droperidol

  Monitor Closely (4)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.
  
  diphenhydramine and droperidol both increase sedation. Use Caution/Monitor.

• duloxetine

  Monitor Closely (1)diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• echothiophate iodide

  Monitor Closely (1)echothiophate iodide increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• eliglustat

  Contraindicated (1)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.

• eluxadoline

  Serious - Use Alternative (1)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.

• encainide

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

• ephedrine

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

• epinephrine

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

• epinephrine racemic

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

• esketamine intranasal

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

• estazolam

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

• ethanol

  Monitor Closely (1)diphenhydramine and ethanol both increase sedation. Use Caution/Monitor.

• etomidate

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

• eucalyptus

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

• fenfluramine

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

• fentanyl

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)diphenhydramine and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flavoxate

  Monitor Closely (1)diphenhydramine and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flecainide

  Monitor Closely (1)diphenhydramine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• flibanserin

  Monitor Closely (1)diphenhydramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluoxetine

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

• fluphenazine

  Monitor Closely (4)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.
  
  diphenhydramine and fluphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurazepam

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

• formoterol

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

• gabapentin

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)galantamine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)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.

• glycopyrrolate

  Monitor Closely (1)diphenhydramine and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrrolate inhaled

  Monitor Closely (1)diphenhydramine and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrronium tosylate topical

  Monitor Closely (1)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

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

• haloperidol

  Monitor Closely (5)diphenhydramine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. 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.
  
  diphenhydramine and haloperidol both increase sedation. Use Caution/Monitor.

• hawthorn

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

• henbane

  Monitor Closely (1)diphenhydramine and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.

• homatropine

  Monitor Closely (1)diphenhydramine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hops

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

• huperzine A

  Monitor Closely (1)huperzine A increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hyaluronidase

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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

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

• hyoscyamine

  Monitor Closely (1)diphenhydramine and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  Monitor Closely (1)diphenhydramine and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

• iloperidone

  Monitor Closely (5)diphenhydramine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. 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.
  
  diphenhydramine and iloperidone both increase sedation. Use Caution/Monitor.

• imipramine

  Monitor Closely (3)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

  Monitor Closely (1)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.

• isocarboxazid

  Serious - Use Alternative (1)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. .

• isoproterenol

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

• kava

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

• ketamine

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

• ketotifen, ophthalmic

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

• lasmiditan

  Monitor Closely (1)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

  Monitor Closely (1)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

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

• levodopa

  Monitor Closely (1)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

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

• lisdexamfetamine

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

• lofepramine

  Monitor Closely (3)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

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

• loprazolam

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

• loratadine

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

• lorazepam

  Monitor Closely (1)diphenhydramine and lorazepam both increase sedation. Use Caution/Monitor.

• lormetazepam

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

• loxapine

  Monitor Closely (4)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.
  
  diphenhydramine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)loxapine inhaled increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor.
  
  diphenhydramine and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)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

  Monitor Closely (2)diphenhydramine and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and maprotiline both increase sedation. Use Caution/Monitor.

• marijuana

  Monitor Closely (1)diphenhydramine and marijuana both increase sedation. Use Caution/Monitor.

• meclizine

  Monitor Closely (1)diphenhydramine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (1)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.

• melatonin

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

• meperidine

  Monitor Closely (1)diphenhydramine and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

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

• metaproterenol

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

• metaxalone

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

• methadone

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

• methamphetamine

  Monitor Closely (2)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

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

• methscopolamine

  Monitor Closely (1)diphenhydramine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methylenedioxymethamphetamine

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

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• metoprolol

  Monitor Closely (1)diphenhydramine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mexiletine

  Monitor Closely (1)diphenhydramine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam

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

• midazolam intranasal

  Monitor Closely (1)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

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

• mirtazapine

  Monitor Closely (1)diphenhydramine and mirtazapine both increase sedation. Use Caution/Monitor.

• modafinil

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

• morphine

  Monitor Closely (2)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

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• nebivolol

  Monitor Closely (1)diphenhydramine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• neostigmine

  Monitor Closely (1)neostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nettle

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

• nitazoxanide

  Minor (1)nitazoxanide, diphenhydramine. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

• norepinephrine

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

• nortriptyline

  Monitor Closely (3)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

  Monitor Closely (4)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.
  
  diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)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

  Monitor Closely (1)onabotulinumtoxinA and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• opium tincture

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

• orphenadrine

  Monitor Closely (2)diphenhydramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and orphenadrine both increase sedation. Use Caution/Monitor.

• ospemifene

  Monitor Closely (1)diphenhydramine, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxazepam

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

• oxybutynin

  Monitor Closely (1)diphenhydramine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin topical

  Monitor Closely (1)diphenhydramine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  Monitor Closely (1)diphenhydramine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  Monitor Closely (2)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.Minor (1)diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymorphone

  Monitor Closely (2)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

  Monitor Closely (4)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.
  
  diphenhydramine and paliperidone both increase sedation. Use Caution/Monitor.

• pancuronium

  Monitor Closely (1)diphenhydramine and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• papaveretum

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

• papaverine

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

• paroxetine

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

• passion flower

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

• pentazocine

  Monitor Closely (1)diphenhydramine and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

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

• perampanel

  Monitor Closely (1)perampanel and diphenhydramine both increase sedation. Use Caution/Monitor.

• perhexiline

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

• perphenazine

  Monitor Closely (4)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.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phendimetrazine

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

• phenelzine

  Monitor Closely (1)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

  Monitor Closely (1)diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.

• phentermine

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

• phenylephrine

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

• phenylephrine PO

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

• pholcodine

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

• physostigmine

  Monitor Closely (1)physostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pilocarpine ophthalmic

  Monitor Closely (1)pilocarpine ophthalmic increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimozide

  Monitor Closely (4)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.
  
  diphenhydramine and pimozide both increase sedation. Use Caution/Monitor.

• pirbuterol

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

• pitolisant

  Serious - Use Alternative (1)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.

• pralidoxime

  Monitor Closely (1)diphenhydramine and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pramlintide

  Serious - Use Alternative (1)pramlintide, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

• pregabalin

  Monitor Closely (1)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

  Monitor Closely (1)diphenhydramine and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (4)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.
  
  diphenhydramine and prochlorperazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

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

• promethazine

  Monitor Closely (4)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.
  
  diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• propafenone

  Monitor Closely (1)diphenhydramine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propantheline

  Monitor Closely (1)diphenhydramine and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

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

• propranolol

  Monitor Closely (1)diphenhydramine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propylhexedrine

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

• protriptyline

  Monitor Closely (2)diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

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

• quetiapine

  Monitor Closely (4)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.
  
  diphenhydramine and quetiapine both increase sedation. Use Caution/Monitor.

• quinidine

  Serious - Use Alternative (1)quinidine, diphenhydramine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of prolonged QTc interval.

• ramelteon

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

• rapacuronium

  Monitor Closely (1)diphenhydramine and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• risperidone

  Monitor Closely (4)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.
  
  diphenhydramine and risperidone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rocuronium

  Monitor Closely (1)diphenhydramine and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sage

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

• salmeterol

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

• scopolamine

  Monitor Closely (1)diphenhydramine and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

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

• secobarbital

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

• sevoflurane

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

• shepherd's purse

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

• Siberian ginseng

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

• sodium oxybate

  Serious - Use Alternative (1)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.

• solifenacin

  Monitor Closely (1)diphenhydramine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• stiripentol

  Monitor Closely (1)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

  Monitor Closely (1)succinylcholine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

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

• tamoxifen

  Monitor Closely (1)diphenhydramine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tamsulosin

  Monitor Closely (1)diphenhydramine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tapentadol

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

• temazepam

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

• terbutaline

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

• thioridazine

  Monitor Closely (4)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.
  
  diphenhydramine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)diphenhydramine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  Monitor Closely (4)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.
  
  diphenhydramine and thiothixene both increase sedation. Use Caution/Monitor.

• timolol

  Monitor Closely (1)diphenhydramine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tiotropium

  Monitor Closely (1)diphenhydramine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolterodine

  Monitor Closely (1)diphenhydramine and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• topiramate

  Monitor Closely (1)diphenhydramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  Monitor Closely (3)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.

• tranylcypromine

  Serious - Use Alternative (1)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. .

• trazodone

  Monitor Closely (1)diphenhydramine and trazodone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• triazolam

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

• triclofos

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

• trifluoperazine

  Monitor Closely (4)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.
  
  diphenhydramine and trifluoperazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trihexyphenidyl

  Monitor Closely (1)diphenhydramine and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimipramine

  Monitor Closely (2)diphenhydramine and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

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

• tropisetron

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

• trospium chloride

  Monitor Closely (1)diphenhydramine and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

• valerian

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

• vecuronium

  Monitor Closely (1)diphenhydramine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• xylometazoline

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

• yohimbine

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

• ziconotide

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

• ziprasidone

  Monitor Closely (4)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.
  
  diphenhydramine and ziprasidone both increase sedation. Use Caution/Monitor.

• zotepine

  Monitor Closely (3)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.
  
  diphenhydramine and zotepine both increase sedation. Use Caution/Monitor.