acetaminophen/aspirin/diphenhydramine (OTC)

Brand and Other Names:Excedrin PM Headache
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

acetaminophen/aspirin/diphenhydramine

caplet

  • 250mg/250mg/38mg (as diphenhydramine citrate; equivalent to 25mg diphenhydramine)

Headache

Indicated for temporary relief of occasional headaches and minor aches and pains with accompanying sleeplessness

2 caplets PO HS prn

Dosage Forms & Strengths

acetaminophen/aspirin/diphenhydramine

caplet

  • 250mg/250mg/38mg (as diphenhydramine citrate; equivalent to 25mg diphenhydramine)

Headache

Indicated for temporary relief of occasional headaches and minor aches and pains with accompanying sleeplessness

<12 years: Safety and efficacy not established

≥12 years: 2 caplets PO HS prn

Next:

Interactions

Interaction Checker

and acetaminophen/aspirin/diphenhydramine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (3)

            • dichlorphenamide

              dichlorphenamide increases levels of aspirin by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

            • 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.

            • mifepristone

              aspirin, mifepristone. Other (see comment). Contraindicated. Comment: Aspirin induced antiplatelet activity may induce excessive bleeding after an abortion w/mifepristone (RU 486).

            Serious - Use Alternative (29)

            • benazepril

              aspirin, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • 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.

            • captopril

              aspirin, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • 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.

            • enalapril

              aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • fosinopril

              aspirin, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ibuprofen

              ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

              ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

            • ibuprofen IV

              ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

              ibuprofen IV decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

            • 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. .

            • ketorolac

              aspirin, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • ketorolac intranasal

              aspirin, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • lesinurad

              aspirin decreases effects of lesinurad by unspecified interaction mechanism. Avoid or Use Alternate Drug. Aspirin at doses >325 mg/day may decrease lesinurad efficacy. Aspirin doses 325 mg/day or less (ie, for cardiovascular event prophylaxis) does not decrease lesinurad efficacy and can be coadministered.

            • lisinopril

              aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • 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.

            • macimorelin

              aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

            • measles, mumps, rubella and varicella vaccine, live

              aspirin, measles, mumps, rubella and varicella vaccine, live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

            • 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.

            • methotrexate

              aspirin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.

            • 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.

            • mifepristone

              aspirin will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mitotane

              aspirin will decrease the level or effect of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • moexipril

              aspirin, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • pemetrexed

              aspirin increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

            • perindopril

              aspirin, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • 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.

            • probenecid

              aspirin decreases effects of probenecid by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Aspirin decreases uricosuric action of probenecid.

            Monitor Closely (528)

            • abciximab

              aspirin, abciximab. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • acalabrutinib

              acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.

            • acebutolol

              acebutolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • aceclofenac

              aceclofenac and aspirin both increase anticoagulation. Use Caution/Monitor.

              aceclofenac and aspirin both increase serum potassium. Use Caution/Monitor.

            • acemetacin

              acemetacin and aspirin both increase anticoagulation. Use Caution/Monitor.

              acemetacin and aspirin both increase serum potassium. Use Caution/Monitor.

            • acetazolamide

              acetazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

              acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • aclidinium

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

            • agrimony

              aspirin and agrimony both increase anticoagulation. Use Caution/Monitor.

            • albuterol

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

              aspirin increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfalfa

              aspirin and alfalfa both increase anticoagulation. Use Caution/Monitor.

            • alfentanil

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

            • alfuzosin

              aspirin decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • aliskiren

              aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • alprazolam

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

            • alteplase

              aspirin, alteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • American ginseng

              aspirin and American ginseng both increase anticoagulation. 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.

            • amiloride

              amiloride and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

            • 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.

            • amoxicillin

              amoxicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              amoxicillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • ampicillin

              ampicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

            • anagrelide

              aspirin, anagrelide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.

              anagrelide, aspirin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.

            • anticholinergic/sedative combos

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

            • antithrombin alfa

              antithrombin alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, antithrombin alfa. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • antithrombin III

              antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, antithrombin III. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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.

            • apixaban

              aspirin and apixaban both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspiriin. Avoid coadministration with chronic use of higher dose aspirin. In 1 trial (APPRAISE-2), therapy was terminated because of significantly increased bleeding when apixaban was administered with dual antiplatelet therapy (eg, aspirin plus clopidogrel) compared with single antiplatelet treatment

            • 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.

              aspirin increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • argatroban

              argatroban and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, argatroban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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

              aspirin decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • atenolol

              atenolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • 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.

            • azficel-T

              azficel-T, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking aspirin may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of aspirin is not recommended. .

            • azilsartan

              aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • 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.

            • bemiparin

              bemiparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • benazepril

              benazepril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

            • bendroflumethiazide

              aspirin increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benperidol

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

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

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

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

            • benzhydrocodone/acetaminophen

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

            • benzphetamine

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

            • benztropine

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

            • betaxolol

              betaxolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • bethanechol

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

            • betrixaban

              aspirin, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

            • bimatoprost

              bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • bisoprolol

              bisoprolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • bivalirudin

              bivalirudin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, bivalirudin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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.

            • brinzolamide

              brinzolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

            • brompheniramine

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

            • bumetanide

              aspirin increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              aspirin decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • 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.

            • candesartan

              candesartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              candesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • caplacizumab

              caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

            • captopril

              captopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, elderly or volume depleted individuals.

            • carbachol

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

            • carbenoxolone

              aspirin increases and carbenoxolone decreases serum potassium. 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

              carvedilol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • celecoxib

              aspirin and celecoxib both increase anticoagulation. Use Caution/Monitor.

              aspirin and celecoxib both increase serum potassium. Use Caution/Monitor.

            • cenobamate

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

            • celiprolol

              celiprolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • chlorothiazide

              aspirin increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. 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.

            • chlorpropamide

              aspirin increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • chlorthalidone

              aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorzoxazone

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

            • choline magnesium trisalicylate

              aspirin and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.

              aspirin and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

            • cilostazol

              aspirin, cilostazol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • cinnamon

              aspirin and cinnamon both increase anticoagulation. Use Caution/Monitor.

            • cinnarizine

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

            • ciprofloxacin

              aspirin decreases levels of ciprofloxacin by Other (see comment). Use Caution/Monitor. Comment: Buffered aspirin may decrease absorption of quinolones. Consider administering 2 hr before or 6 hr after, buffered aspirin administration.

            • cisatracurium

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

            • citalopram

              citalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

            • 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).

            • clobetasone

              aspirin, clobetasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • clomipramine

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

              clomipramine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.

              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.

            • clopidogrel

              aspirin, clopidogrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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.

            • collagenase clostridium histolyticum

              aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

            • cordyceps

              aspirin and cordyceps both increase anticoagulation. Use Caution/Monitor.

            • cortisone

              aspirin, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

            • cyclopenthiazide

              aspirin increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cyproheptadine

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

            • dabigatran

              dabigatran and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin

            • dalteparin

              dalteparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, dalteparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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 .

            • darifenacin

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

            • deferasirox

              deferasirox, aspirin. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.

            • defibrotide

              defibrotide increases effects of aspirin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

            • deflazacort

              aspirin, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

            • desirudin

              aspirin, desirudin. Either increases levels of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • deutetrabenazine

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

            • dexamethasone

              aspirin, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

            • diclofenac

              aspirin and diclofenac both increase anticoagulation. Use Caution/Monitor.

              aspirin and diclofenac both increase serum potassium. Use Caution/Monitor.

            • dicloxacillin

              dicloxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

            • dicyclomine

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

            • diethylpropion

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

            • difenoxin hcl

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

            • diflunisal

              aspirin and diflunisal both increase anticoagulation. Use Caution/Monitor.

              aspirin and diflunisal both increase serum potassium. Use Caution/Monitor.

            • digoxin

              aspirin and digoxin both increase serum potassium. 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.

            • dipyridamole

              aspirin, dipyridamole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • dobutamine

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

              aspirin increases and dobutamine decreases serum potassium. 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.

            • dong quai

              aspirin and dong quai both increase anticoagulation. Use Caution/Monitor.

            • dopamine

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

            • dopexamine

              aspirin increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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.

            • doxazosin

              aspirin decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • drospirenone

              drospirenone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

            • duloxetine

              duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              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.

            • edoxaban

              edoxaban, aspirin. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

            • eltrombopag

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • enalapril

              enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

            • enoxaparin

              enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI

              aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • ephedrine

              aspirin increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

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

            • epinephrine

              aspirin increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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.

              aspirin increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epoprostenol

              aspirin and epoprostenol both increase anticoagulation. Use Caution/Monitor.

            • esketamine intranasal

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

            • eprosartan

              eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • eptifibatide

              aspirin, eptifibatide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • escitalopram

              escitalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • esmolol

              esmolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • estazolam

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

            • ethacrynic acid

              aspirin increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ethanol

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

            • etodolac

              aspirin and etodolac both increase anticoagulation. Use Caution/Monitor.

              aspirin and etodolac both increase serum potassium. 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.

            • fenbufen

              aspirin and fenbufen both increase anticoagulation. Use Caution/Monitor.

              aspirin and fenbufen both increase serum potassium. Use Caution/Monitor.

            • fenfluramine

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

            • fennel

              aspirin and fennel both increase anticoagulation. Use Caution/Monitor.

            • fenoprofen

              aspirin and fenoprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin and fenoprofen both increase serum potassium. Use Caution/Monitor.

            • fentanyl

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

            • fentanyl intranasal

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

            • fentanyl transdermal

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

            • fentanyl transmucosal

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

            • fesoterodine

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

            • feverfew

              aspirin and feverfew both increase anticoagulation. 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.

            • fish oil

              fish oil, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • 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.

            • fludrocortisone

              aspirin, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

            • fluoxetine

              fluoxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • fluphenazine

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

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

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

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

            • flurazepam

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

            • flurbiprofen

              aspirin and flurbiprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin and flurbiprofen both increase serum potassium. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding SSRIs inhib. serotonin uptake by platelets.

            • fondaparinux

              fondaparinux and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • formoterol

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

              aspirin increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • forskolin

              aspirin and forskolin both increase anticoagulation. 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.

            • fosinopril

              fosinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

            • furosemide

              aspirin increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • 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.

            • garlic

              aspirin and garlic both increase anticoagulation. Use Caution/Monitor.

            • gentamicin

              aspirin increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ginger

              aspirin and ginger both increase anticoagulation. Use Caution/Monitor.

            • ginkgo biloba

              aspirin and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

            • glimepiride

              aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • glipizide

              aspirin increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • glyburide

              aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • 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.

            • green tea

              green tea increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.

            • griseofulvin

              griseofulvin decreases levels of aspirin by unknown mechanism. Use Caution/Monitor.

            • 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.

            • heparin

              heparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin, heparin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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.

            • horse chestnut seed

              aspirin and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

            • huperzine A

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

            • hyaluronidase

              aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, 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.

              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.

            • hydralazine

              aspirin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • hydrochlorothiazide

              aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrocortisone

              aspirin, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

            • ibrutinib

              ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • ibuprofen

              aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • ibuprofen IV

              aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.

              aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.

              aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

            • icosapent

              icosapent, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time; monitor periodically if coadministered with other drugs that affect bleeding.

            • 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.

            • imatinib

              imatinib, aspirin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

            • 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.

            • indapamide

              aspirin increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indomethacin

              aspirin and indomethacin both increase anticoagulation. Use Caution/Monitor.

              aspirin and indomethacin both increase serum potassium. Use Caution/Monitor.

            • insulin aspart

              aspirin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin aspart protamine/insulin aspart

              aspirin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin degludec

              aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin degludec/insulin aspart

              aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin detemir

              aspirin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin glargine

              aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin glulisine

              aspirin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin inhaled

              aspirin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin isophane human/insulin regular human

              aspirin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin lispro

              aspirin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin lispro protamine/insulin lispro

              aspirin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin NPH

              aspirin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • insulin regular human

              aspirin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

            • 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.

            • irbesartan

              irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • 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.

              aspirin increases and isoproterenol decreases serum potassium. 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.

            • ketoprofen

              aspirin and ketoprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin and ketoprofen both increase serum potassium. Use Caution/Monitor.

            • ketamine

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

            • ketorolac

              aspirin and ketorolac both increase anticoagulation. Use Caution/Monitor.

              aspirin and ketorolac both increase serum potassium. Use Caution/Monitor.

            • ketorolac intranasal

              aspirin and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.

              aspirin and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

            • ketotifen, ophthalmic

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

            • labetalol

              labetalol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • latanoprost

              latanoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • latanoprostene bunod ophthalmic

              latanoprostene bunod ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • 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

              aspirin increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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. .

            • levomilnacipran

              levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • 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.

            • lisinopril

              lisinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

            • lithium

              aspirin increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

            • lixisenatide

              lixisenatide 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.

            • lornoxicam

              aspirin and lornoxicam both increase anticoagulation. Use Caution/Monitor.

              aspirin and lornoxicam both increase serum potassium. Use Caution/Monitor.

            • losartan

              losartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • 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.

            • meclofenamate

              aspirin and meclofenamate both increase anticoagulation. Use Caution/Monitor.

              aspirin and meclofenamate both increase serum potassium. Use Caution/Monitor.

            • mefenamic acid

              aspirin and mefenamic acid both increase anticoagulation. Use Caution/Monitor.

              aspirin and mefenamic acid both increase serum potassium. Use Caution/Monitor.

            • melatonin

              melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.

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

            • meloxicam

              aspirin and meloxicam both increase anticoagulation. Use Caution/Monitor.

              aspirin and meloxicam both increase serum potassium. Use Caution/Monitor.

            • meperidine

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

            • meprobamate

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

            • mesalamine

              mesalamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.

            • metaproterenol

              aspirin increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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.

            • methazolamide

              methazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

            • 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.

            • methyclothiazide

              aspirin increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • methylenedioxymethamphetamine

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

            • methylprednisolone

              aspirin, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • metolazone

              aspirin increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metoprolol

              metoprolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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 intranasal

              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.

            • milnacipran

              milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • midazolam

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

            • midazolam intranasal

              midazolam intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

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

            • 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.

            • mistletoe

              aspirin increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • modafinil

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

            • moexipril

              moexipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.

            • 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.

            • moxisylyte

              aspirin decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • moxonidine

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

            • mycophenolate

              aspirin will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • nabilone

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

            • nabumetone

              aspirin and nabumetone both increase anticoagulation. Use Caution/Monitor.

              aspirin and nabumetone both increase serum potassium. Use Caution/Monitor.

            • nadolol

              nadolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • nafcillin

              nafcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              nafcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • nalbuphine

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

            • naproxen

              aspirin and naproxen both increase anticoagulation. Use Caution/Monitor.

              aspirin and naproxen both increase serum potassium. Use Caution/Monitor.

            • nebivolol

              nebivolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • nefazodone

              nefazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • neostigmine

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

            • nettle

              aspirin increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nitazoxanide

              nitazoxanide, aspirin. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

            • nitroglycerin rectal

              aspirin will increase the level or effect of nitroglycerin rectal by Other (see comment). Use Caution/Monitor. The pharmacological effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

            • nitroglycerin sublingual

              aspirin increases effects of nitroglycerin sublingual by additive vasodilation. Use Caution/Monitor. Vasodilatory and hemodynamic effects of NTG may be enhanced by coadministration with aspirin (additive effect desirable for emergent treatment).

            • norepinephrine

              aspirin increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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.

            • olmesartan

              olmesartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              olmesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • 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.

            • omega 3 carboxylic acids

              omega 3 carboxylic acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

            • omega 3 fatty acids

              omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

            • 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.

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

            • oxacillin

              oxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              oxacillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • oxazepam

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

            • oxaprozin

              aspirin and oxaprozin both increase anticoagulation. Use Caution/Monitor.

              aspirin and oxaprozin both increase serum potassium. 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.

            • panax ginseng

              aspirin and panax ginseng both increase anticoagulation. Use Caution/Monitor.

            • 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.

            • parecoxib

              aspirin and parecoxib both increase anticoagulation. Use Caution/Monitor.

              aspirin and parecoxib both increase serum potassium. Use Caution/Monitor.

            • paroxetine

              paroxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • passion flower

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

            • pau d'arco

              aspirin and pau d'arco both increase anticoagulation. Use Caution/Monitor.

            • pegaspargase

              pegaspargase increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

            • penbutolol

              penbutolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • penicillin G aqueous

              penicillin G aqueous, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              penicillin G aqueous, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • 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.

            • perindopril

              perindopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin,in elderly or volume depleted individuals.

            • 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. .

            • phenindione

              phenindione and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • phenobarbital

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

            • phenoxybenzamine

              aspirin decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • phentermine

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

            • phentolamine

              aspirin decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • phytoestrogens

              aspirin and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

            • pilocarpine

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

            • pilocarpine ophthalmic

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

            • pimozide

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

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

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

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

            • pindolol

              pindolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • pirbuterol

              aspirin increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

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

            • piroxicam

              aspirin and piroxicam both increase anticoagulation. Use Caution/Monitor.

              aspirin and piroxicam both increase serum potassium. Use Caution/Monitor.

            • pralidoxime

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

            • pivmecillinam

              pivmecillinam, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              pivmecillinam, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • potassium acid phosphate

              aspirin and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium chloride

              aspirin and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium citrate

              aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

            • potassium iodide

              potassium iodide and aspirin both increase serum potassium. Use Caution/Monitor.

            • prasugrel

              aspirin, prasugrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • prazosin

              aspirin decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • prednisolone

              aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • prednisone

              aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • 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.

              propranolol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • propylhexedrine

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

            • protamine

              protamine and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • 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.

            • quinapril

              quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

            • ramelteon

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

            • ramipril

              ramipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.

            • rapacuronium

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

            • reishi

              aspirin and reishi both increase anticoagulation. Use Caution/Monitor.

            • reteplase

              aspirin, reteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • 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.

            • rivaroxaban

              aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

            • rivastigmine

              rivastigmine increases toxicity of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

            • rocuronium

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

            • sacubitril/valsartan

              sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • salicylates (non-asa)

              aspirin and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.

              aspirin and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

            • salmeterol

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

              aspirin increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salsalate

              aspirin and salsalate both increase anticoagulation. Use Caution/Monitor.

              aspirin and salsalate both increase serum potassium. Use Caution/Monitor.

            • scopolamine

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

            • saw palmetto

              saw palmetto increases toxicity of aspirin by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

            • scullcap

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

            • secobarbital

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

            • selumetinib

              aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

            • sertraline

              sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • Siberian ginseng

              aspirin and Siberian ginseng both increase anticoagulation. 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.

            • silodosin

              aspirin decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • solifenacin

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

            • sotalol

              sotalol and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • spironolactone

              spironolactone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

              aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.

            • 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

              aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.

              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.

            • sulfamethoxazole

              aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

            • sulfasalazine

              aspirin and sulfasalazine both increase anticoagulation. Use Caution/Monitor.

              aspirin and sulfasalazine both increase serum potassium. Use Caution/Monitor.

            • sulindac

              aspirin and sulindac both increase anticoagulation. Use Caution/Monitor.

              aspirin and sulindac both increase serum potassium. Use Caution/Monitor.

            • tafluprost

              tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • 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.

            • telmisartan

              telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • temazepam

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

            • temocillin

              temocillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              temocillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • tenecteplase

              aspirin, tenecteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • terazosin

              aspirin decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • terbutaline

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

              aspirin increases and terbutaline decreases serum potassium. 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.

            • ticagrelor

              aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.

            • 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.

            • ticarcillin

              ticarcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              ticarcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • timolol

              timolol and aspirin both increase serum potassium. Use Caution/Monitor.

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

              aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • 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.

            • tirofiban

              aspirin, tirofiban. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

            • tobramycin inhaled

              tobramycin inhaled and aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolazamide

              aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolbutamide

              aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolfenamic acid

              aspirin and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.

              aspirin and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              aspirin and tolmetin both increase anticoagulation. Use Caution/Monitor.

              aspirin and tolmetin both increase serum potassium. Use Caution/Monitor.

            • tolterodine

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

            • tolvaptan

              aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • topiramate

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

            • torsemide

              aspirin increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • 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.

            • trandolapril

              trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.

            • travoprost ophthalmic

              travoprost ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • trazodone

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

              trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • triamcinolone acetonide injectable suspension

              aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.

            • triazolam

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

            • triamterene

              triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

            • 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.

            • valproic acid

              aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

            • valsartan

              valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • vecuronium

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

            • venlafaxine

              venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

            • voclosporin

              voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • vorapaxar

              aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

              aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

            • vortioxetine

              aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

            • warfarin

              warfarin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. The need for simultaneous use of low-dose aspirin and warfarin are common for patients with cardiovascular disease; monitor closely.

              acetaminophen increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • xylometazoline

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

            • yohimbine

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

            • zanubrutinib

              aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

            • ziconotide

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

            • ziprasidone

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

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

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

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

            • zotepine

              aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

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

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

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

            Minor (191)

            • aceclofenac

              aceclofenac will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              acemetacin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acetazolamide

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

            • acyclovir

              aspirin will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • albiglutide

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

            • alendronate

              aspirin, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

            • aluminum hydroxide

              aluminum hydroxide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • amikacin

              aspirin increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • aminohippurate sodium

              aspirin will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • anamu

              aspirin and anamu both increase anticoagulation. 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.

            • ascorbic acid

              ascorbic acid will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              aspirin decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.

              ascorbic acid increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

            • ashwagandha

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

            • balsalazide

              aspirin will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bemiparin

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

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bismuth subsalicylate

              bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. 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.

            • bumetanide

              aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

            • calcium carbonate

              calcium carbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • carbamazepine

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

            • cefadroxil

              cefadroxil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefepime

              cefepime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefixime

              cefixime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefprozil

              cefprozil will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftazidime

              ceftazidime will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftibuten

              ceftibuten will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              aspirin will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpromazine

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

            • chlorpropamide

              aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • chlorthalidone

              chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. 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.

            • choline magnesium trisalicylate

              aspirin will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chromium

              aspirin increases levels of chromium by unspecified interaction mechanism. 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.

            • cortisone

              cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • creatine

              creatine, aspirin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

            • cyanocobalamin

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

            • cyclopenthiazide

              cyclopenthiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • dalteparin

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

            • danshen

              aspirin and danshen both increase anticoagulation. Minor/Significance Unknown.

            • deflazacort

              deflazacort decreases levels of aspirin by increasing renal clearance. 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.

            • devil's claw

              aspirin and devil's claw both increase anticoagulation. Minor/Significance Unknown.

            • dexamethasone

              dexamethasone decreases levels of aspirin by increasing renal clearance. 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.

            • diclofenac

              aspirin will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diclofenac topical

              diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

            • diflunisal

              aspirin will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diltiazem

              diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • 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.

            • eplerenone

              aspirin decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • 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.

              ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

            • ethosuximide

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

            • etodolac

              aspirin will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • 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.

            • fenbufen

              aspirin will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fenoprofen

              aspirin will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fesoterodine

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

            • feverfew

              aspirin decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone decreases levels of aspirin by increasing renal clearance. 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.

            • flurbiprofen

              aspirin will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • folic acid

              aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. 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.

            • furosemide

              aspirin decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • gabapentin

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

            • gabapentin enacarbil

              gabapentin enacarbil 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.

            • ganciclovir

              aspirin will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • gentamicin

              aspirin increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • glimepiride

              aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • glipizide

              aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • glyburide

              aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • 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.

            • hydrochlorothiazide

              hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • ibuprofen

              aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • imidapril

              aspirin decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • indapamide

              indapamide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indomethacin

              aspirin will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • isoniazid

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

            • ketoprofen

              aspirin will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac

              aspirin will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac intranasal

              aspirin will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • L-methylfolate

              aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. 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.

            • lornoxicam

              aspirin will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meclofenamate

              aspirin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mefenamic acid

              aspirin will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meloxicam

              aspirin will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mesalamine

              aspirin will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methsuximide

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

            • methyclothiazide

              methyclothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • metoclopramide

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

            • metolazone

              metolazone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metronidazole

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

            • nabumetone

              aspirin will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • naproxen

              aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • neomycin PO

              aspirin increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • 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.

            • noni juice

              aspirin and noni juice both increase serum potassium. Minor/Significance Unknown.

            • ofloxacin

              ofloxacin, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

            • oxaprozin

              aspirin will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. 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.

            • parecoxib

              aspirin will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • paromomycin

              aspirin increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • paroxetine

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

            • penicillin VK

              penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

            • pentazocine

              aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

            • 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.

            • piperacillin

              piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

            • piroxicam

              aspirin will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • prednisolone

              prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • prednisone

              prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • 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.

            • rose hips

              rose hips will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              aspirin decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.

              rose hips increases levels of aspirin by decreasing renal clearance. 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.

            • 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.

            • salicylates (non-asa)

              aspirin will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • salsalate

              aspirin will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sodium bicarbonate

              sodium bicarbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • sodium citrate/citric acid

              sodium citrate/citric acid, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

            • stiripentol

              aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • streptomycin

              aspirin increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • sulfadiazine

              aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulfasalazine

              aspirin will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulfisoxazole

              aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulindac

              aspirin will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • teniposide

              aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

            • tiagabine

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

            • tiludronate

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

            • tobramycin

              aspirin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • tolazamide

              aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • tolbutamide

              aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

            • tolfenamic acid

              aspirin will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tolmetin

              aspirin will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • 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.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

            • triamterene

              triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.

              aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

            • 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.

            • valganciclovir

              aspirin will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • valproic acid

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

            Previous
            Next:

            Adverse Effects

            Frequency Not Defined (Acetaminophen)

            Angioedema, laryngeal edema

            Pruritic maculopapular rash, urticaria

            Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura

            Hepatotoxicity

            May increase uric acid, chloride, glucose

            May decrease sodium, calcium, bicarbonate

            Anaphylactoid reaction

            Frequency Not Defined (Aspirin)

            Rash, urticaria

            Dyspepsia, heartburn, nausea, stomach pain, vomiting

            Tinnitus (high or chronic dose)

            Frequency Not Defined (Diphenhydramine)

            Sedation

            Confusion

            May decrease cognitive function in geriatric patients

            Anticholinergic effects

            Blurred vision

            Diplopia

            Xerostomia

            Dry nasal mucosa

            Pharyngeal dryness

            Thick bronchial sputum

            Constipation

            Urinary retention

            Agranulocytosis

            Hemolytic anemia

            Thrombocytopenia

            Convulsions

            Tachycardia

            Palpitations

            Hypotension

            Nervousness

            Restlessness

            Euphoria

            Vertigo

            Menstrual irregularities

            Anorexia

            Neuritis

            Tinnitus

            Previous
            Next:

            Warnings

            Contraindications

            Allergy to acetaminophen, aspirin, or diphenhydramine products

            Coadministration with other acetaminophen containing medications; increased risk for severe hepatic impairment

            Coadministration with other diphenhydramine containing products (even topical diphenhydramine)

            Cautions

            Acetaminophen

            • Hepatic impairment or consumption of 3 or more alcoholic beverages/day may increase risk for liver damage (associated with acetaminophen)
            • Do not take with other products that contain acetaminophen due to risk of additive toxicity/overdose
            • Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

            Aspirin

            • Children and adolescents should not use aspirin for symptoms of viral infections (eg, chickenpox, influenza) due to risk for Reye syndrome
            • Risk for GI bleeding
            • Avoid with active peptic ulcer disease
            • Avoid in severe renal impairment (ie, CrCl <10 mL/min)

            Diphenhydramine

            • May cause CNS depression, which can impair driving or operating heavy machinery
            • May potentiate effects of sedatives such as alcohol
            • Use caution in patients with angle-closure glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, thyroid dysfunction
            • Elderly patients: Considered high-risk medication for this age group because it may increase risk of falls and has high incidence of anticholinergic effects; may exacerbate existing lower urinary tract conditions or benign prostatic hyperplasia; use in special situations may be appropriate; not recommended for treatment of insomnia, because tolerance develops and risk of anticholinergic effects increases
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Avoid aspirin (NSAIDs) during pregnancy, particularly in third trimester because of risk for premature closure of the ductus arteriosus

            Lactation

            Information below is from LactMed (a TOXNET database)

            Aspirin

            • Excreted in human breast milk as the salicylate metabolite
            • Avoid high-dose during lactation; may take low-dose aspirin (ie, 75-162 mg/day) and avoid breastfeeding for 1-2 hr after dose to minimize antiplatelet effects on infant

            Acetaminophen

            • Excreted in low levels in human breast milk; amount in milk is much less than doses usually given to infants

            Diphenhydramine

            • No studies using modern assay methods to detect drug levels in breast milk have been reported
            • Small, occasional doses of diphenhydramine would not be expected to cause any adverse effects in breastfed infants
            • Larger doses or more prolonged use may cause effects in the infant or decrease the milk supply

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Acetaminophen: Inhibits prostaglandin synthesis in CNS and may block peripheral pain impulse generation; acts on hypothalamus as antipyretic

            Aspirin: Acts on hypothalamus to produce antipyresis; anti-inflammatory properties attributed to prostaglandin synthetase inhibition resulting in decreased formation of thromboxane A2

            Diphenhydramine: Histamine H1-receptor antagonist with sedative properties

            Previous
            Next:

            Administration

            Instructions

            Swallow caplet with full glass of water

            Storage

            Store at room temperature (20-25°C [68-77°F])

            Close bottle cap tightly after use

            Previous
            Next:

            Images

            No images available for this drug.
            Previous
            Next:

            Patient Handout

            A Patient Handout is not currently available for this monograph.
            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.