acetaminophen/diphenhydramine/dextromethorphan (OTC)

Cold & Flu

Indicated for relief of cold and flu symptoms

10 mL PO q4hr PRN; not to exceed 6 doses/24 hr

Cold & Flu

Indicated for relief of cold and flu symptoms

<6 years: Safety and efficacy not established

6-12 years: 5 mL PO q4hr PRN; not to exceed 6 doses/24 hr

>12 years: As adults; 10 mL PO q4hr PRN; not to exceed 6 doses/24 hr

Contraindicated (1)

• eliglustat

  diphenhydramine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

Serious - Use Alternative (12)

• calcium/magnesium/potassium/sodium oxybates

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

• eluxadoline

  diphenhydramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.

• isocarboxazid

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

• lonafarnib

  acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• mefloquine

  mefloquine increases toxicity of diphenhydramine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• metoclopramide intranasal

  diphenhydramine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• olopatadine intranasal

  diphenhydramine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• pexidartinib

  acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• pitolisant

  diphenhydramine decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

• pramlintide

  pramlintide, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

• pretomanid

  acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• quinidine

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

Monitor Closely (297)

• aclidinium

  diphenhydramine and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• acrivastine

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

• albuterol

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

• alfentanil

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

• alprazolam

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

• amantadine

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

• amifampridine

  diphenhydramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amisulpride

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

• amitriptyline

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

• amobarbital

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

• amoxapine

  diphenhydramine and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and amoxapine both increase sedation. Use Caution/Monitor.

• anticholinergic/sedative combos

  anticholinergic/sedative combos and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• apalutamide

  apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• apomorphine

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

• arformoterol

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

• aripiprazole

  diphenhydramine and aripiprazole both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.
  
  aripiprazole increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• armodafinil

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

• asenapine

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

• asenapine transdermal

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

• atogepant

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

• atomoxetine

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

• atracurium

  atracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  atropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine IV/IM

  atropine IV/IM and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• avapritinib

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

• axitinib

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

• azelastine

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

• baclofen

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

• belladonna alkaloids

  belladonna alkaloids and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belladonna and opium

  diphenhydramine and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and belladonna and opium both increase sedation. Use Caution/Monitor.

• benperidol

  diphenhydramine and benperidol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  benperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• benzhydrocodone/acetaminophen

  diphenhydramine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.
  
  benzhydrocodone/acetaminophen and diphenhydramine both increase sedation. Use Caution/Monitor.

• benzphetamine

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

• benztropine

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

• bethanechol

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

• brexanolone

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

• brexpiprazole

  diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and diphenhydramine both increase sedation. Use Caution/Monitor.

• brimonidine

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

• brivaracetam

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

• brompheniramine

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

• bupivacaine implant

  acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and diphenhydramine both increase sedation. Use Caution/Monitor.

• busulfan

  acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• carbachol

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

• carbinoxamine

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

• carisoprodol

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

• carvedilol

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

• cenobamate

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

• cevimeline

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

• chloral hydrate

  diphenhydramine and chloral hydrate both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

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

• chlorpheniramine

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

• chlorpromazine

  diphenhydramine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  chlorpromazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• chlorzoxazone

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

• cinnarizine

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

• cisatracurium

  cisatracurium and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• clemastine

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

• clobazam

  diphenhydramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  diphenhydramine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clorazepate

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

• clozapine

  diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• codeine

  diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.

• cyclizine

  cyclizine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and diphenhydramine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  cyclobenzaprine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyproheptadine

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

• dantrolene

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

• dapsone topical

  acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  diphenhydramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  darifenacin and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• desflurane

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

• desipramine

  diphenhydramine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and desipramine both increase sedation. Use Caution/Monitor.

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

  diazepam intranasal, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dicyclomine

  dicyclomine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

  diphenhydramine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dimenhydrinate

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

• diphenoxylate hcl

  diphenhydramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

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

• dobutamine

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

• donepezil

  donepezil increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• donepezil transdermal

  donepezil transdermal, diphenhydramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

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

• dopexamine

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

• dosulepin

  diphenhydramine and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  diphenhydramine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and doxepin both increase sedation. Use Caution/Monitor.

• doxylamine

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

• droperidol

  diphenhydramine and droperidol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  droperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• duloxetine

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

• echothiophate iodide

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

• eltrombopag

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

• ephedrine

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

• epinephrine

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

• epinephrine racemic

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

• esketamine intranasal

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

• estazolam

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

• ethanol

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

• etomidate

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

• exenatide injectable solution

  exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• fenfluramine

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

• fentanyl

  fentanyl, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl intranasal

  fentanyl intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl intranasal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl iontophoretic transdermal system

  fentanyl iontophoretic transdermal system and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transdermal

  fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transmucosal

  fentanyl transmucosal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fesoterodine

  diphenhydramine and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• finerenone

  acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flavoxate

  diphenhydramine and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flecainide

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

• flibanserin

  diphenhydramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• fluphenazine

  diphenhydramine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  fluphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• imatinib

  imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.

• flurazepam

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

• formoterol

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

• gabapentin

  gabapentin, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  gabapentin enacarbil, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  galantamine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ganaxolone

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

• glycopyrrolate

  diphenhydramine and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrrolate inhaled

  diphenhydramine and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrronium tosylate topical

  glycopyrronium tosylate topical, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• gotu kola

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

• haloperidol

  diphenhydramine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and haloperidol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  haloperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hawthorn

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

• henbane

  diphenhydramine and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.

• homatropine

  diphenhydramine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hops

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

• huperzine A

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

• hyaluronidase

  diphenhydramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydrocodone

  diphenhydramine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• hydromorphone

  diphenhydramine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

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

• hyoscyamine

  diphenhydramine and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  diphenhydramine and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

• iloperidone

  diphenhydramine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and iloperidone both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  iloperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• imipramine

  diphenhydramine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and imipramine both increase sedation. Use Caution/Monitor.

• ipratropium

  diphenhydramine and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• isavuconazonium sulfate

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

• isoniazid

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

• isoproterenol

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

• ivacaftor

  acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• kava

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

• ketamine

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

• ketotifen, ophthalmic

  diphenhydramine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lasmiditan

  lasmiditan, diphenhydramine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• lemborexant

  acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
  
  lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• levalbuterol

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

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levodopa

  diphenhydramine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

• levorphanol

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

• lisdexamfetamine

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

• lixisenatide (DSC)

  lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

  diphenhydramine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

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

• lomitapide

  acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• loprazolam

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

• lorazepam

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

• lormetazepam

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

• loxapine

  diphenhydramine and loxapine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  loxapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• loxapine inhaled

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

• lurasidone

  lurasidone, diphenhydramine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  diphenhydramine and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and maprotiline both increase sedation. Use Caution/Monitor.

• marijuana

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

• meclizine

  diphenhydramine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• melatonin

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

• meperidine

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

• meprobamate

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

• metaproterenol

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

• metaxalone

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

• methadone

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

• methamphetamine

  diphenhydramine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

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

• methscopolamine

  diphenhydramine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methylenedioxymethamphetamine

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

• metoprolol

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

• mexiletine

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

• midazolam

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

• midazolam intranasal

  midazolam intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• midodrine

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

• mipomersen

  mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirtazapine

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

• modafinil

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

• morphine

  diphenhydramine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and morphine both increase sedation. Use Caution/Monitor.

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• nebivolol

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

• neostigmine

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

• norepinephrine

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

• nortriptyline

  diphenhydramine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both increase sedation. Use Caution/Monitor.

• olanzapine

  diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  olanzapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• oliceridine

  diphenhydramine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• onabotulinumtoxinA

  onabotulinumtoxinA and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• opium tincture

  diphenhydramine and opium tincture both increase sedation. Use Caution/Monitor.

• orphenadrine

  diphenhydramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and orphenadrine both increase sedation. Use Caution/Monitor.

• ospemifene

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

• oxazepam

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

• oxybutynin

  diphenhydramine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin topical

  diphenhydramine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  diphenhydramine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  diphenhydramine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  diphenhydramine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  diphenhydramine and paliperidone both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  paliperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pancuronium

  diphenhydramine and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• papaveretum

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

• papaverine

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

• passion flower

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

• pentazocine

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

• pentobarbital

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

• perampanel

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

• perphenazine

  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• phendimetrazine

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

• phenelzine

  phenelzine increases effects of diphenhydramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenobarbital

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

• phentermine

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

• phenylephrine

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

• phenylephrine PO

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

• pholcodine

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

• physostigmine

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

• pilocarpine

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

• pimozide

  diphenhydramine and pimozide both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pimozide increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pirbuterol

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

• pralidoxime

  diphenhydramine and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pregabalin

  pregabalin, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primidone

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

• prochlorperazine

  diphenhydramine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  prochlorperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• promethazine

  diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• propafenone

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

• propantheline

  diphenhydramine and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

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

• propranolol

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

• propylhexedrine

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

• protriptyline

  diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.

• pyridostigmine

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

• quazepam

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

• quetiapine

  diphenhydramine and quetiapine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  quetiapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ramelteon

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

• rapacuronium

  diphenhydramine and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• risperidone

  diphenhydramine and risperidone both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  risperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• rocuronium

  diphenhydramine and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• salmeterol

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

• scopolamine

  diphenhydramine and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

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

• secobarbital

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

• sevoflurane

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

• shepherd's purse

  diphenhydramine and shepherd's purse both increase sedation. Use Caution/Monitor.

• solifenacin

  diphenhydramine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• stiripentol

  stiripentol, diphenhydramine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• succinylcholine

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

• sufentanil

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

• tamoxifen

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

• tamsulosin

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

• tapentadol

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

• tazemetostat

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

• temazepam

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

• terbutaline

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

• tetracaine

  tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  diphenhydramine and thioridazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thioridazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• thiothixene

  diphenhydramine and thiothixene both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thiothixene increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• timolol

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

• tinidazole

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

• tiotropium

  diphenhydramine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolterodine

  diphenhydramine and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• topiramate

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

• tramadol

  diphenhydramine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  diphenhydramine and tramadol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• trazodone

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

• triazolam

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

• triclofos

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

• trifluoperazine

  diphenhydramine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trifluoperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• trihexyphenidyl

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

• trimipramine

  diphenhydramine and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

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

• trospium chloride

  diphenhydramine and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

• valerian

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

• vecuronium

  diphenhydramine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• warfarin

  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• xylometazoline

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

Minor (82)

• acetazolamide

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

• albiglutide

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

• antithrombin alfa

  acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• argatroban

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

• aripiprazole

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

• ashwagandha

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

• bemiparin

  acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• bivalirudin

  acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• brimonidine

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

• carbamazepine

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

• chlorpromazine

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

• cholestyramine

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

• clonazepam

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

• colestipol

  colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• dalteparin

  acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• desipramine

  diphenhydramine and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  desipramine and diphenhydramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• dexfenfluramine

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

• dextroamphetamine

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

• dextromethorphan

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

• diazepam

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

• dimenhydrinate

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

• disulfiram

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

• donepezil

  diphenhydramine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  donepezil decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

• doxepin

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

• encainide

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

• enoxaparin

  acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• ethanol

  ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethosuximide

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

• eucalyptus

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

• felbamate

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

• fesoterodine

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

• fluoxetine

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

• fluphenazine

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

• fondaparinux

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

• fosphenytoin

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

• galantamine

  diphenhydramine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  galantamine decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

• green tea

  green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• heparin

  acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• isoniazid

  isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• lacosamide

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

• lamotrigine

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

• levetiracetam

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

• liraglutide

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

• loratadine

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

• lorazepam

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

• methsuximide

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

• metoclopramide

  metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metronidazole

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

• nettle

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

• nitazoxanide

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

• oxcarbazepine

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

• oxybutynin

  oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• paroxetine

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

• perhexiline

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

• perphenazine

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

• phenindione

  acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

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

• phenytoin

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

• primidone

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

• prochlorperazine

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

• promazine

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

• promethazine

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

• protamine

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

• rifabutin

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

• rifampin

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

• risperidone

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

• rufinamide

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

• ruxolitinib

  acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

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

• Siberian ginseng

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

• tiagabine

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

• tolterodine

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

• topiramate

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

• trazodone

  diphenhydramine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• trifluoperazine

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

• tropisetron

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

• valproic acid

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

• acetazolamide

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

• aclidinium

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

• acrivastine

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

• albiglutide

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

• 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.

• amisulpride

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

• 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.

• antithrombin alfa

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

• antithrombin III

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

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

• apomorphine

  Monitor Closely (1)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.

• argatroban

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

• 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.

• asenapine

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

• asenapine transdermal

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

• ashwagandha

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

• atogepant

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

• atomoxetine

  Monitor Closely (1)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.

• avapritinib

  Monitor Closely (2)acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  avapritinib and diphenhydramine both increase sedation. Use Caution/Monitor.

• axitinib

  Monitor Closely (1)acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  Monitor Closely (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.

• bemiparin

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

• 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 (2)diphenhydramine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.
  
  benzhydrocodone/acetaminophen and diphenhydramine both increase sedation. Use Caution/Monitor.

• benzphetamine

  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.

• bivalirudin

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

• brexanolone

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

• brexpiprazole

  Monitor Closely (2)diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.
  
  brexpiprazole and diphenhydramine both increase sedation. Use Caution/Monitor.

• brimonidine

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

• brivaracetam

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

• brompheniramine

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

• bupivacaine implant

  Monitor Closely (1)acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• buprenorphine, long-acting injection

  Monitor Closely (1)buprenorphine, long-acting injection and diphenhydramine both increase sedation. Use Caution/Monitor.

• busulfan

  Monitor Closely (1)acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

• butabarbital

  Monitor Closely (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.

• carbamazepine

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

• 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.

• cholestyramine

  Minor (1)cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cinnarizine

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

• 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.

• colestipol

  Minor (1)colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (2)cyclizine 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.

• dalteparin

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

• dantrolene

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

• dapsone topical

  Monitor Closely (1)acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  Monitor Closely (1)diphenhydramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

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

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, 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.

• difelikefalin

  Monitor Closely (1)difelikefalin and diphenhydramine both increase sedation. 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.

• disulfiram

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

• 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.

• donepezil transdermal

  Monitor Closely (1)donepezil transdermal, diphenhydramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• 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.

• eltrombopag

  Monitor Closely (1)eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• 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.

• enoxaparin

  Minor (1)acetaminophen increases effects of enoxaparin by unknown mechanism. 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.Minor (2)ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

• ethosuximide

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

• etomidate

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

• eucalyptus

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

• exenatide injectable solution

  Monitor Closely (1)exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  Monitor Closely (1)exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• felbamate

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

• fenfluramine

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

• fentanyl

  Monitor Closely (2)fentanyl, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl intranasal

  Monitor Closely (2)fentanyl intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl intranasal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl iontophoretic transdermal system

  Monitor Closely (1)fentanyl iontophoretic transdermal system and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transdermal

  Monitor Closely (2)fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transmucosal

  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.

• finerenone

  Monitor Closely (1)acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• 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 (2)diphenhydramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• 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.

• fondaparinux

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

• formoterol

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

• fosphenytoin

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

• gabapentin

  Monitor Closely (1)gabapentin, 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.

• ganaxolone

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

• 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.

• green tea

  Minor (1)green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• 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.

• heparin

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

• 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.

• imatinib

  Monitor Closely (1)imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.

• imipramine

  Monitor Closely (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.

• isavuconazonium sulfate

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

• isocarboxazid

  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. .

• isoniazid

  Monitor Closely (1)isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.Minor (1)isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• isoproterenol

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

• ivacaftor

  Monitor Closely (1)acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• kava

  Monitor Closely (1)kava increases effects of 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.

• lacosamide

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

• lamotrigine

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

• lasmiditan

  Monitor Closely (1)lasmiditan, 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 (2)acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
  
  lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• levalbuterol

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

• levetiracetam

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

• 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. .

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (2)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levorphanol

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

• liraglutide

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

• lisdexamfetamine

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

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

  Monitor Closely (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.

• lomitapide

  Monitor Closely (1)acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loprazolam

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

• 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.

• methsuximide

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

• methylenedioxymethamphetamine

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

• metoclopramide

  Minor (1)metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• metronidazole

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

• 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 (2)midazolam intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• midodrine

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

• mipomersen

  Monitor Closely (1)mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirtazapine

  Monitor Closely (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.

• olopatadine intranasal

  Serious - Use Alternative (1)diphenhydramine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• 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.

• oxcarbazepine

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

• oxybutynin

  Monitor Closely (1)diphenhydramine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (1)diphenhydramine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Monitor Closely (1)diphenhydramine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• 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.

• pexidartinib

  Serious - Use Alternative (1)acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• phendimetrazine

  Monitor Closely (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. .

• phenindione

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

• phenobarbital

  Monitor Closely (1)diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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. .

• phenytoin

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

• 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.

• 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.

• pretomanid

  Serious - Use Alternative (1)acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• primidone

  Monitor Closely (1)diphenhydramine and primidone both increase sedation. Use Caution/Monitor.Minor (1)primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• protamine

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

• 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.

• rifabutin

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

• rifampin

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

• risperidone

  Monitor Closely (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.

• rufinamide

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

• ruxolitinib

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• tazemetostat

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

• temazepam

  Monitor Closely (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.

• tetracaine

  Monitor Closely (1)tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  Monitor Closely (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.

• tiagabine

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

• timolol

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

• tinidazole

  Monitor Closely (1)acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 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.Minor (1)topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• 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.

• valproic acid

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

• vecuronium

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

• warfarin

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

• zonisamide

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

• 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.