naproxen/diphenhydramine (OTC)

Brand and Other Names:Aleve PM
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

naproxen/diphenhydramine

tablet

  • 220mg/25mg

Sleeplessness due to Pain

2 tablets (440mg/50mg) PO at bedtime PRN

Dosage Forms & Strengths

naproxen/diphenhydramine

tablet

  • 220mg/25mg

Sleeplessness due to Pain

<12 years: Safety and efficacy not established

≥12 years: 2 tablets (440mg/50mg) PO at bedtime PRN

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Interactions

Interaction Checker

and naproxen/diphenhydramine

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            Contraindicated (1)

            • eliglustat

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

            Serious - Use Alternative (32)

            • aminolevulinic acid oral

              aminolevulinic acid oral, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              naproxen, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • apixaban

              naproxen and apixaban both decrease anticoagulation. Avoid or Use Alternate Drug.

            • benazepril

              naproxen, 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

              naproxen, 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

              naproxen, 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

              naproxen, 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 will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • ibuprofen IV

              ibuprofen IV will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. therapeutic duplication; increased risk of gastric ulceration

              ibuprofen IV and naproxen both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen IV and naproxen both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • 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

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

            • ketorolac intranasal

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

            • lisinopril

              naproxen, 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.

            • 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

              naproxen increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity.

            • methyl aminolevulinate

              naproxen, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • 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.

            • moexipril

              naproxen, 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

              naproxen 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

              naproxen, 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.

            • 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.

            • quinapril

              naproxen, quinapril. 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.

            • quinidine

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

            • ramipril

              naproxen, ramipril. 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.

            • sodium oxybate

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

            • tacrolimus

              naproxen, tacrolimus. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant administration increases risk of nephrotoxicity.

            • thioridazine

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

            • trandolapril

              naproxen, trandolapril. 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.

            • tranylcypromine

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

            Monitor Closely (472)

            • acebutolol

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

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

            • aceclofenac

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

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

            • acemetacin

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

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

            • aclidinium

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

            • agrimony

              naproxen 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.

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

            • alfalfa

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

            • alfentanil

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

            • alfuzosin

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

            • aliskiren

              naproxen 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

              naproxen and alteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • American ginseng

              naproxen 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 naproxen 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.

            • anticholinergic/sedative combos

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

            • antithrombin alfa

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

            • antithrombin III

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

            • 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.

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

            • argatroban

              argatroban and naproxen both increase anticoagulation. Modify Therapy/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

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

            • aspirin

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

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

            • aspirin rectal

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

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

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate and naproxen both increase anticoagulation. Use Caution/Monitor.

              aspirin/citric acid/sodium bicarbonate and naproxen both increase serum potassium. Use Caution/Monitor.

            • atenolol

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

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

            • atomoxetine

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

            • atracurium

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

            • atropine

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

            • atropine IV/IM

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

            • azelastine

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

            • azilsartan

              naproxen, 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.

              naproxen 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 naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • benazepril

              benazepril, naproxen. 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.

            • bendroflumethiazide

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

              naproxen 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

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

            • bimatoprost

              bimatoprost, naproxen. 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 naproxen both increase serum potassium. Use Caution/Monitor.

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

            • bivalirudin

              bivalirudin and naproxen both increase anticoagulation. Modify Therapy/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.

            • brompheniramine

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

            • budesonide

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

            • bumetanide

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

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • candesartan

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

              naproxen 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, naproxen. 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.

            • captopril

              captopril, naproxen. 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.

            • carbachol

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

            • carbenoxolone

              naproxen 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

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

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

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

            • celecoxib

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

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

            • cenobamate

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

            • celiprolol

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

              naproxen 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

              naproxen 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

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

            • chlorthalidone

              naproxen 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

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

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

            • cinnamon

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

            • cinnarizine

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

            • ciprofloxacin

              naproxen, ciprofloxacin. Other (see comment). Modify Therapy/Monitor Closely. Comment: Mechanism: unknown. Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • cisatracurium

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

            • citalopram

              citalopram, naproxen. 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

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

            • clomipramine

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

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

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

            • clonazepam

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

            • clopidogrel

              clopidogrel, naproxen. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Clopidogrel and NSAIDs both inhibit platelet aggregation.

            • 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.

            • cordyceps

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

            • cortisone

              naproxen, 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

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

            • cyclosporine

              naproxen, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • cyproheptadine

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

            • dabigatran

              dabigatran and naproxen both increase anticoagulation. Use Caution/Monitor. Caution is advised, both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

            • dalteparin

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

            • dantrolene

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

            • darifenacin

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

            • deferasirox

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

            • defibrotide

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

            • deflazacort

              naproxen, 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.

            • deutetrabenazine

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

            • dexamethasone

              naproxen, 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.

            • dichlorphenamide

              dichlorphenamide and naproxen both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

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

              diclofenac and naproxen both increase serum potassium. 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

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

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

            • digoxin

              naproxen 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.

            • dobutamine

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

              naproxen 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

              naproxen 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

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

              naproxen increases and dopexamine decreases serum potassium. 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

              naproxen 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 naproxen both increase serum potassium. Modify Therapy/Monitor Closely.

            • duloxetine

              duloxetine, naproxen. 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, naproxen. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding, monitor closely. Promptly evaluate any signs or symptoms of blood loss.

            • eltrombopag

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, naproxen. 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.

            • emtricitabine

              emtricitabine, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine 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, naproxen. 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.

            • enoxaparin

              enoxaparin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ephedrine

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

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

            • epinephrine

              naproxen 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.

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

            • epoprostenol

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

              naproxen 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, naproxen. 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.

            • escitalopram

              escitalopram, naproxen. 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 naproxen both increase serum potassium. Use Caution/Monitor.

              naproxen 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

              naproxen 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

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

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

            • etomidate

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

            • fenfluramine

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

            • fennel

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

            • fenoprofen

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

              fenoprofen and naproxen 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

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

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of naproxen 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.

            • fludrocortisone

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

            • fluoxetine

              fluoxetine, naproxen. 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

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

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

            • fluvoxamine

              fluvoxamine, naproxen. 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 naproxen 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.

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

            • forskolin

              naproxen 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, naproxen. 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.

            • furosemide

              naproxen 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

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

            • gemifloxacin

              gemifloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glimepiride

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

            • glipizide

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

            • glyburide

              naproxen 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, naproxen. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

            • 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 naproxen both increase anticoagulation. Modify Therapy/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

              naproxen 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

              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

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

            • hydrochlorothiazide

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

            • 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.

            • hydrocortisone

              naproxen, 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 naproxen 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.

            • 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, naproxen. 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

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

            • indomethacin

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

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

            • ipratropium

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

            • irbesartan

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

              naproxen 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, naproxen. 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.

            • isoproterenol

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

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

            • kava

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

            • ketoprofen

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

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

            • ketamine

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

            • ketorolac

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

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

            • ketorolac intranasal

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

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

            • ketotifen, ophthalmic

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

            • labetalol

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

              naproxen 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, naproxen. 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, naproxen. 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

              lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • levalbuterol

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

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

            • levodopa

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

            • levofloxacin

              levofloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

            • levomilnacipran

              levomilnacipran, naproxen. 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, naproxen. 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.

            • lithium

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

            • lofepramine

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

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

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

            • lofexidine

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

            • loprazolam

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

            • lorazepam

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

            • lormetazepam

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

            • lornoxicam

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

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

            • losartan

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

              naproxen 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, naproxen. 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

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

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

            • mefenamic acid

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

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

            • melatonin

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

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

            • meloxicam

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

              meloxicam and naproxen 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, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.

            • metaproterenol

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

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

            • metaxalone

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

            • methyclothiazide

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

            • methadone

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

            • methamphetamine

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

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

            • methocarbamol

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

            • methscopolamine

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

            • methylenedioxymethamphetamine

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

            • methylprednisolone

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

            • metolazone

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

            • metoprolol

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

              naproxen 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.

            • milnacipran

              milnacipran, naproxen. 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, naproxen. 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

              naproxen 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, naproxen. 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.

            • 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.

            • moxifloxacin

              moxifloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • moxisylyte

              naproxen 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

              naproxen 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

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

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

            • nadolol

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

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

            • nalbuphine

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

            • nebivolol

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

              naproxen 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, naproxen. 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

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

            • norepinephrine

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

              naproxen 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, naproxen. 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.

            • 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.

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

            • oxaprozin

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

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

            • oxazepam

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

            • oxybutynin

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

            • oxybutynin topical

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

            • oxybutynin transdermal

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

            • oxycodone

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

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

            • oxymorphone

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

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

            • paliperidone

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

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

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

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

            • panax ginseng

              naproxen 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

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

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

            • paroxetine

              paroxetine, naproxen. 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

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

            • pegaspargase

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

            • peginterferon alfa 2b

              peginterferon alfa 2b decreases levels of naproxen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered.

            • penbutolol

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

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

            • 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, naproxen. 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.

            • 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 naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • phenobarbital

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

            • phenoxybenzamine

              naproxen 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

              naproxen 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

              naproxen 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.

            • 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 naproxen both increase serum potassium. Use Caution/Monitor.

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

            • pirbuterol

              naproxen 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

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

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

            • pralidoxime

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

            • pivmecillinam

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

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

            • potassium acid phosphate

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

            • potassium chloride

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

            • potassium citrate

              naproxen and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium iodide

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

            • pralatrexate

              naproxen increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor. NSAIDs may delay pralatrexate clearance, increasing drug exposure. Adjust the pralatrexate dose as needed.

            • prasugrel

              naproxen, prasugrel. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Chronic use of NSAIDs with prasugrel may increase bleeding risk.

            • prazosin

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

            • prednisolone

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

            • prednisone

              naproxen, 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.

            • probenecid

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

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

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

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

            • propylhexedrine

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

            • protamine

              protamine and naproxen 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, naproxen. 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.

            • ramelteon

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

            • ramipril

              ramipril, naproxen. 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.

            • rapacuronium

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

            • reishi

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

            • reteplase

              naproxen and reteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • 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

              rivaroxaban, naproxen. Other (see comment). Use Caution/Monitor. Comment: NSAIDs are known to increase bleeding. Bleeding risk may be increased when NSAIDs are used concomitantly with rivaroxaban. Monitor for signs/symptoms of blood loss.

            • rivastigmine

              rivastigmine increases toxicity of naproxen 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 naproxen both increase serum potassium. Use Caution/Monitor.

              sacubitril/valsartan, naproxen. 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.

              naproxen 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)

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

              naproxen 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.

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

            • salsalate

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

              naproxen 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 naproxen 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.

            • sertraline

              sertraline, naproxen. 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

              naproxen 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

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

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              naproxen, 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 naproxen 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 naproxen 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/polyethylene glycol

              naproxen, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • solifenacin

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

            • sotalol

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

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

            • spironolactone

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

            • 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

              naproxen 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.

            • sulfasalazine

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

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

            • sulindac

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

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

            • tafluprost

              tafluprost, naproxen. 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.

            • telmisartan

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

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

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

            • tenecteplase

              naproxen and tenecteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • tenofovir DF

              tenofovir DF, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF 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.

            • terazosin

              naproxen 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.

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

            • thioridazine

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

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

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

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

            • ticarcillin

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

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

            • thiothixene

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

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

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

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

            • timolol

              timolol and naproxen 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.

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

            • tiotropium

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

            • tobramycin inhaled

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

            • tolazamide

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

            • tolbutamide

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

            • tolfenamic acid

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

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

            • tolmetin

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

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

            • tolterodine

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

            • tolvaptan

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

            • topiramate

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

            • torsemide

              naproxen 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, naproxen. 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.

            • travoprost ophthalmic

              travoprost ophthalmic, naproxen. 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, naproxen. 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

              naproxen, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of NSAIDS and corticosteroids increases the risk of gastrointestinal side effects. .

            • triazolam

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

            • triamterene

              triamterene and naproxen 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.

            • valsartan

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

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

            • vitamin K1 (phytonadione)

              naproxen increases and vitamin K1 (phytonadione) decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • voclosporin

              voclosporin, naproxen. 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

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

            • vortioxetine

              naproxen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

            • warfarin

              warfarin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • 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

              naproxen, 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

              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.

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

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

            Minor (104)

            • aceclofenac

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

            • acemetacin

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

            • acyclovir

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

            • alendronate

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

            • amikacin

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

            • aminohippurate sodium

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

            • anamu

              naproxen and anamu both increase anticoagulation. Minor/Significance Unknown.

            • aripiprazole

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

            • ashwagandha

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

            • aspirin

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

            • aspirin rectal

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

            • aspirin/citric acid/sodium bicarbonate

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

            • balsalazide

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

            • bendroflumethiazide

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

            • brimonidine

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

            • cefadroxil

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

            • cefamandole

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

            • cefpirome

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

            • ceftibuten

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

            • celecoxib

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

            • cephalexin

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

            • chlorothiazide

              chlorothiazide will increase the level or effect of naproxen 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

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

            • chlorthalidone

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

            • choline magnesium trisalicylate

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

            • creatine

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

            • cyclopenthiazide

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

            • danshen

              naproxen and danshen both increase anticoagulation. 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

              naproxen and devil's claw both increase anticoagulation. 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.

            • diclofenac

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

            • diclofenac topical

              diclofenac topical, naproxen. 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

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

            • dimenhydrinate

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

            • donepezil

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

              donepezil decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • doxepin

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

            • encainide

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

            • eplerenone

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

            • etodolac

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

            • eucalyptus

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

            • fenoprofen

              fenoprofen will increase the level or effect of naproxen 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

              naproxen decreases effects of feverfew by pharmacodynamic antagonism. 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

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

            • furosemide

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

            • 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

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

            • gentamicin

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

            • hydrochlorothiazide

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

            • imidapril

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

            • indapamide

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

            • indomethacin

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

            • ketoprofen

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

            • ketorolac

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

            • ketorolac intranasal

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

            • loratadine

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

            • lornoxicam

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

            • meclofenamate

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

            • mefenamic acid

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

            • meloxicam

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

            • mesalamine

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

            • methyclothiazide

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

            • metolazone

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

            • nabumetone

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

            • neomycin PO

              naproxen 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.

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

            • noni juice

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

            • oxycodone

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

            • ofloxacin

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

            • oxaprozin

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

            • parecoxib

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

            • paromomycin

              naproxen 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.

            • 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.

            • piroxicam

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

            • prochlorperazine

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

            • promazine

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

            • promethazine

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

            • risperidone

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

            • rose hips

              rose hips will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. 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)

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

            • salsalate

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

            • streptomycin

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

            • sulfasalazine

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

            • sulindac

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

            • tobramycin

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

            • tolfenamic acid

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

            • tolmetin

              naproxen 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.

            • trazodone

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

            • triamterene

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

              naproxen 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

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

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            Adverse Effects

            1-10%

            Naproxen

            • Abdominal pain
            • GI bleeding
            • Nausea
            • Edema
            • Fluid retention

            Diphenhydramine

            • Sedation
            • Anticholinergic effects
            • Xerostomia
            • Blurred vision
            • Palpitations
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            Warnings

            Black Box Warnings

            Cardiovascular risk

            • Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
            • Risk may increase with duration of use
            • Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
            • NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery

            Gastrointestinal risk

            • NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal GI adverse events may occur at any time during use and without warning symptoms
            • Elderly patients are at greater risk for serious GI events

            Contraindications

            Hypersensitivity

            Naproxen

            • Absolute: Aspirin allergy; perioperative pain in setting of coronary artery bypass graft (CABG) surgery
            • Relative: Bleeding disorders, delayed esophageal transit, hepatic disease, peptic ulcer, renal impairment, stomatitis, late pregnancy (may cause premature closure of ductus arteriosus

            Diphenhydramine

            • Coadministration with MAOIs

            Cautions

            Naproxen

            • Use caution in congestive heart failure (CHF), hypertension, renal/hepatic impairment, or aspirin sensitive asthma
            • If taking aspirin for heart attack or stroke, ask healthcare professional before using this drug; NSAIDs may decrease benefits of aspirin
            • May increase risk of aseptic meningitis, especially in patients with systemic lupus erythematosis and mixed connective tissue disorders
            • Prolonged use may increase risk of adverse cardiovascular events
            • May cause anaphylactoid reactions, even in patients with no prior exposure to NSAIDs
            • Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
            • May cause drowsiness, dizziness, and blurred vision
            • Platelet aggregation and adhesion may be decreased; may prolong bleeding time; monitor closely patients with coagulation disorders
            • May increase risk of hyperkalemia in the elderly, renal disease, or diabetics, especially when used concomitantly with drugs that increase hyperkalemia
            • May cause serious skin reactions including exfoliative dermatitis, toxic epidermal syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue therapy at first sign of skin rash

            Diphenhydramine

            • Driving or operating machinery
            • May potentiate effects of sedatives such as alcohol
            • Narrow-angle glaucoma
            • Prostatic hypertrophy
            • Stenosing peptic ulcer, pyloroduodenal obstruction
            • Bladder neck obstruction
            • 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
            • Debilitated patients
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            Pregnancy & Lactation

            Pregnancy category (naproxen): C; D if used for prolonged periods or after 31-32 weeks gestation; may cause premature closure of ductus arteriosus

            Naproxen: Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and approximately 2.6% of controls

            Lactation: Naproxen and diphenhydramine are excreted in human breast milk; effect on infant unknown; not recommended

            Pregnant or breastfeeding patients should seek advice of health professional before using OTC drugs

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Naproxen: Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2

            Diphenhydramine: Histamine H1-receptor antagonist that elicits sedative effects

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            Images

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            Patient Handout

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