naproxen/diphenhydramine (OTC)

Dosing Forms & Strengths

naproxen/diphenhydramine

tablet

• 220mg/25mg

Sleeplessness due to Pain

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

Sleeplessness due to Pain

<12 years: Safety and efficacy not established

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

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 (33)

• 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.

• olopatadine intranasal

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

• 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 (480)

• 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.

• acrivastine

  acrivastine and diphenhydramine both increase sedation. 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.

• amisulpride

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

• amitriptyline

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

• amobarbital

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

• amoxapine

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

• anticholinergic/sedative combos

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

• 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

  asenapine and diphenhydramine both increase sedation. Use Caution/Monitor.
  
  naproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• asenapine transdermal

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

• 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.

• avapritinib

  avapritinib and diphenhydramine both increase sedation. 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).

• 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.

• daridorexant

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

• darifenacin

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

• 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.

• difelikefalin

  difelikefalin and diphenhydramine both increase sedation. 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.

• donepezil transdermal

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

• dopamine

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

• dopexamine

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

• ganaxolone

  diphenhydramine and ganaxolone both increase sedation. 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.

• sparsentan

  naproxen and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.

• 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

  naproxen, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Drugs with antiplatelet properties may increase anticoagulation effect of warfarin.

• 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.

• acebutolol

  Monitor Closely (2)naproxen decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  acebutolol and naproxen both increase serum potassium. Use Caution/Monitor.

• aceclofenac

  Monitor Closely (2)aceclofenac and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  aceclofenac and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)aceclofenac will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (2)acemetacin and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  acemetacin and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)acemetacin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aclidinium

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

• acrivastine

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

• acyclovir

  Minor (1)naproxen will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  Monitor Closely (1)naproxen and agrimony both increase anticoagulation. Use Caution/Monitor.

• albuterol

  Monitor Closely (2)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.

• alendronate

  Minor (1)naproxen, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

• alfalfa

  Monitor Closely (1)naproxen and alfalfa both increase anticoagulation. Use Caution/Monitor.

• alfentanil

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

• alfuzosin

  Monitor Closely (1)naproxen decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• aliskiren

  Monitor Closely (1)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

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

• alteplase

  Monitor Closely (1)naproxen and alteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• amantadine

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

• American ginseng

  Monitor Closely (1)naproxen and American ginseng both increase anticoagulation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)diphenhydramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amikacin

  Minor (1)naproxen increases levels of amikacin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• amiloride

  Monitor Closely (1)amiloride and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.

• aminohippurate sodium

  Minor (1)naproxen will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• amisulpride

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

• amitriptyline

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

• amobarbital

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

• amoxapine

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

• anamu

  Minor (1)naproxen and anamu both increase anticoagulation. Minor/Significance Unknown.

• anticholinergic/sedative combos

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

• antithrombin alfa

  Monitor Closely (1)antithrombin alfa and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• antithrombin III

  Monitor Closely (1)antithrombin III and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• apixaban

  Serious - Use Alternative (1)naproxen and apixaban both decrease anticoagulation. Avoid or Use Alternate Drug.

• apomorphine

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

• arformoterol

  Monitor Closely (2)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

  Monitor Closely (1)argatroban and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• aripiprazole

  Monitor Closely (4)diphenhydramine decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.
  
  aripiprazole increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and aripiprazole both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

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

• asenapine

  Monitor Closely (2)asenapine and diphenhydramine both increase sedation. Use Caution/Monitor.
  
  naproxen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• asenapine transdermal

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

• ashwagandha

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

• aspirin

  Monitor Closely (2)aspirin and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  Monitor Closely (2)aspirin rectal and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin rectal and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)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

  Monitor Closely (2)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.Minor (1)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.

• atenolol

  Monitor Closely (2)naproxen decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  atenolol and naproxen both increase serum potassium. Use Caution/Monitor.

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• avapritinib

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

• azelastine

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

• azilsartan

  Monitor Closely (2)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

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

• balsalazide

  Minor (1)naproxen will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• belladonna alkaloids

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

• belladonna and opium

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

• bemiparin

  Monitor Closely (1)bemiparin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• benazepril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• bendroflumethiazide

  Monitor Closely (1)naproxen increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)bendroflumethiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• benperidol

  Monitor Closely (4)diphenhydramine decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  benperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)diphenhydramine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• benzphetamine

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

• benztropine

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

• betaxolol

  Monitor Closely (2)naproxen decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  betaxolol and naproxen both increase serum potassium. Use Caution/Monitor.

• bethanechol

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

• betrixaban

  Monitor Closely (1)naproxen, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bimatoprost

  Monitor Closely (1)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

  Monitor Closely (2)naproxen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  bisoprolol and naproxen both increase serum potassium. Use Caution/Monitor.

• bivalirudin

  Monitor Closely (1)bivalirudin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• brexanolone

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

• brexpiprazole

  Monitor Closely (1)diphenhydramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• brimonidine

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

• brompheniramine

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

• budesonide

  Monitor Closely (1)naproxen, budesonide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• bumetanide

  Monitor Closely (2)naproxen decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  naproxen increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• buprenorphine

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

• buprenorphine buccal

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

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)diphenhydramine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• candesartan

  Monitor Closely (3)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.
  
  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 and naproxen both increase serum potassium. Use Caution/Monitor.

• captopril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• carbachol

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

• carbenoxolone

  Monitor Closely (1)naproxen increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbinoxamine

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

• carisoprodol

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

• carvedilol

  Monitor Closely (3)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.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftibuten

  Minor (1)ceftibuten will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (2)celecoxib and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  celecoxib and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)celecoxib will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (2)naproxen decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  celiprolol and naproxen both increase serum potassium. Use Caution/Monitor.

• cenobamate

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

• cephalexin

  Minor (1)cephalexin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cevimeline

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

• chloral hydrate

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

• chlordiazepoxide

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

• chlorothiazide

  Monitor Closely (1)naproxen increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpheniramine

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

• chlorpromazine

  Monitor Closely (4)diphenhydramine decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  chlorpromazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and chlorpromazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  Monitor Closely (1)naproxen increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)naproxen will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorthalidone

  Monitor Closely (1)naproxen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorzoxazone

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

• choline magnesium trisalicylate

  Monitor Closely (2)naproxen and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cinnamon

  Monitor Closely (1)naproxen and cinnamon both increase anticoagulation. Use Caution/Monitor.

• cinnarizine

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

• ciprofloxacin

  Monitor Closely (1)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

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

• citalopram

  Monitor Closely (1)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

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

• clobazam

  Monitor Closely (1)diphenhydramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  Monitor Closely (4)diphenhydramine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  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 and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clopidogrel

  Monitor Closely (1)clopidogrel, naproxen. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Clopidogrel and NSAIDs both inhibit platelet aggregation.

• clorazepate

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

• clozapine

  Monitor Closely (4)diphenhydramine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and clozapine both increase sedation. Use Caution/Monitor.

• codeine

  Monitor Closely (2)diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.

• cordyceps

  Monitor Closely (1)naproxen and cordyceps both increase anticoagulation. Use Caution/Monitor.

• cortisone

  Monitor Closely (1)naproxen, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• creatine

  Minor (1)creatine, naproxen. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

• cyclizine

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

• cyclobenzaprine

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

• cyclopenthiazide

  Monitor Closely (1)naproxen increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)cyclopenthiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)naproxen, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

• cyproheptadine

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

• dabigatran

  Monitor Closely (1)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

  Monitor Closely (1)dalteparin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• danshen

  Minor (1)naproxen and danshen both increase anticoagulation. Minor/Significance Unknown.

• dantrolene

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

• daridorexant

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

• darifenacin

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

• deferasirox

  Monitor Closely (1)deferasirox, naproxen. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.

• defibrotide

  Monitor Closely (1)defibrotide increases effects of naproxen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  Monitor Closely (1)naproxen, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• desflurane

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

• desipramine

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

• deutetrabenazine

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

• devil's claw

  Minor (1)naproxen and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (1)naproxen, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromethorphan

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

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and naproxen both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  Monitor Closely (2)diclofenac and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  diclofenac and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)diclofenac will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  Minor (1)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.

• dicyclomine

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

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• diflunisal

  Monitor Closely (2)diflunisal and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  diflunisal and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)diflunisal will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (1)naproxen and digoxin both increase serum potassium. Use Caution/Monitor.

• dimenhydrinate

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

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

  Monitor Closely (2)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

  Monitor Closely (1)donepezil increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)diphenhydramine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  donepezil decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

• donepezil transdermal

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

• dong quai

  Monitor Closely (1)naproxen and dong quai both increase anticoagulation. Use Caution/Monitor.

• dopamine

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

• dopexamine

  Monitor Closely (2)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

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

• doxazosin

  Monitor Closely (1)naproxen decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• doxepin

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

• doxylamine

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

• droperidol

  Monitor Closely (4)diphenhydramine decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  droperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and droperidol both increase sedation. Use Caution/Monitor.

• drospirenone

  Monitor Closely (1)drospirenone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.

• duloxetine

  Monitor Closely (2)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

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

• edoxaban

  Monitor Closely (1)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.

• eliglustat

  Contraindicated (1)diphenhydramine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• eltrombopag

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

• eluxadoline

  Serious - Use Alternative (1)diphenhydramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• encainide

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

• enoxaparin

  Monitor Closely (1)enoxaparin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• ephedrine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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.

• eplerenone

  Minor (1)naproxen decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• epoprostenol

  Monitor Closely (1)naproxen and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• eprosartan

  Monitor Closely (3)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 and naproxen both increase serum potassium. Use Caution/Monitor.
  
  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

  Monitor Closely (1)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.

• esketamine intranasal

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

• esmolol

  Monitor Closely (2)naproxen decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  esmolol and naproxen both increase serum potassium. Use Caution/Monitor.

• estazolam

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

• ethacrynic acid

  Monitor Closely (1)naproxen increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethanol

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

• etodolac

  Monitor Closely (2)etodolac and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  etodolac and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)etodolac will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• etomidate

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

• eucalyptus

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

• fenfluramine

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

• fennel

  Monitor Closely (1)naproxen and fennel both increase anticoagulation. Use Caution/Monitor.

• fenoprofen

  Monitor Closely (2)fenoprofen and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  fenoprofen and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)fenoprofen will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Monitor Closely (1)fentanyl, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fentanyl intranasal

  Monitor Closely (1)fentanyl intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fentanyl transdermal

  Monitor Closely (1)fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fentanyl transmucosal

  Monitor Closely (1)fentanyl transmucosal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fesoterodine

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

• feverfew

  Monitor Closely (1)naproxen and feverfew both increase anticoagulation. Use Caution/Monitor.Minor (1)naproxen decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• fish oil triglycerides

  Monitor Closely (1)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

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

• flecainide

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

• flibanserin

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

• fludrocortisone

  Monitor Closely (1)naproxen, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• fluoxetine

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

• fluphenazine

  Monitor Closely (4)diphenhydramine decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  fluphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and fluphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurazepam

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

• flurbiprofen

  Monitor Closely (2)flurbiprofen and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  flurbiprofen and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)flurbiprofen will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)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

  Monitor Closely (1)fondaparinux and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• formoterol

  Monitor Closely (2)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

  Monitor Closely (1)naproxen and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• furosemide

  Monitor Closely (1)naproxen increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)naproxen decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• gabapentin

  Monitor Closely (1)gabapentin, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  Monitor Closely (1)galantamine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)diphenhydramine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  galantamine decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

• ganaxolone

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

• ganciclovir

  Minor (1)naproxen will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• garlic

  Monitor Closely (1)naproxen and garlic both increase anticoagulation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• gentamicin

  Monitor Closely (1)naproxen increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)naproxen increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• ginger

  Monitor Closely (1)naproxen and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  Monitor Closely (1)naproxen and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• glimepiride

  Monitor Closely (1)naproxen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glipizide

  Monitor Closely (1)naproxen increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glyburide

  Monitor Closely (1)naproxen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• glycopyrrolate

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

• glycopyrrolate inhaled

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

• glycopyrronium tosylate topical

  Monitor Closely (1)glycopyrronium tosylate topical, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• gotu kola

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

• green tea

  Monitor Closely (1)green tea, naproxen. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

• haloperidol

  Monitor Closely (5)diphenhydramine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  haloperidol increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and haloperidol both increase sedation. Use Caution/Monitor.

• hawthorn

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

• henbane

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

• heparin

  Monitor Closely (1)heparin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• homatropine

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

• hops

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

• horse chestnut seed

  Monitor Closely (1)naproxen and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

• huperzine A

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

• hyaluronidase

  Monitor Closely (1)diphenhydramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  Monitor Closely (1)naproxen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  Monitor Closely (1)naproxen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocodone

  Monitor Closely (1)diphenhydramine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• hydrocortisone

  Monitor Closely (1)naproxen, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• hydromorphone

  Monitor Closely (2)diphenhydramine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

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

• hyoscyamine

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

• hyoscyamine spray

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

• ibrutinib

  Monitor Closely (1)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.

• ibuprofen

  Serious - Use Alternative (3)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

  Serious - Use Alternative (3)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

• iloperidone

  Monitor Closely (5)diphenhydramine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  iloperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and iloperidone both increase sedation. Use Caution/Monitor.

• imatinib

  Monitor Closely (1)imatinib, 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.

• imidapril

  Minor (1)naproxen decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• imipramine

  Monitor Closely (3)diphenhydramine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and imipramine both increase sedation. Use Caution/Monitor.

• indapamide

  Monitor Closely (1)naproxen increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)indapamide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  Monitor Closely (2)indomethacin and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  indomethacin and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)indomethacin will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ipratropium

  Monitor Closely (1)diphenhydramine and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• irbesartan

  Monitor Closely (3)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.
  
  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 and naproxen both increase serum potassium. Use Caution/Monitor.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid increases effects of diphenhydramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• isoproterenol

  Monitor Closely (2)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

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

• ketamine

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

• ketoprofen

  Monitor Closely (2)ketoprofen and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  ketoprofen and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)ketoprofen will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)ketorolac and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  ketorolac and naproxen both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)naproxen, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)ketorolac will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)ketorolac intranasal and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  ketorolac intranasal and naproxen both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)naproxen, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)ketorolac intranasal will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketotifen, ophthalmic

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

• labetalol

  Monitor Closely (2)naproxen decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  labetalol and naproxen both increase serum potassium. Use Caution/Monitor.

• lasmiditan

  Monitor Closely (1)lasmiditan, diphenhydramine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• latanoprost

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• levalbuterol

  Monitor Closely (2)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

  Monitor Closely (1)diphenhydramine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

• levofloxacin

  Monitor Closely (1)levofloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• levomilnacipran

  Monitor Closely (1)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

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

• lisdexamfetamine

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

• lisinopril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• lithium

  Monitor Closely (1)naproxen increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

• lofepramine

  Monitor Closely (3)diphenhydramine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

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

• loprazolam

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

• loratadine

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

• lorazepam

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

• lormetazepam

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

• lornoxicam

  Monitor Closely (2)lornoxicam and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  lornoxicam and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)lornoxicam will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (3)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.
  
  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 and naproxen both increase serum potassium. Use Caution/Monitor.

• loxapine

  Monitor Closely (4)diphenhydramine decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  loxapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

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

• lurasidone

  Monitor Closely (1)lurasidone, diphenhydramine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

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

• marijuana

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

• meclizine

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

• meclofenamate

  Monitor Closely (2)meclofenamate and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  meclofenamate and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)meclofenamate will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)mefenamic acid and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  mefenamic acid and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)mefenamic acid will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefloquine

  Serious - Use Alternative (1)mefloquine increases toxicity of diphenhydramine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• melatonin

  Monitor Closely (2)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

  Monitor Closely (2)meloxicam and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  meloxicam and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)meloxicam will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meperidine

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

• meprobamate

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

• mesalamine

  Monitor Closely (1)mesalamine, naproxen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.Minor (1)naproxen will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (2)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

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

• methadone

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

• methamphetamine

  Monitor Closely (2)diphenhydramine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

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

• methotrexate

  Serious - Use Alternative (1)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.

• methscopolamine

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

• methyclothiazide

  Monitor Closely (1)naproxen increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)methyclothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyl aminolevulinate

  Serious - Use Alternative (1)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.

• methylenedioxymethamphetamine

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

• methylprednisolone

  Monitor Closely (1)naproxen, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• metoclopramide intranasal

  Serious - Use Alternative (1)diphenhydramine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)naproxen increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)metolazone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)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

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

• midazolam

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

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

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

• milnacipran

  Monitor Closely (1)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.

• mipomersen

  Monitor Closely (1)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

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

• mistletoe

  Monitor Closely (1)naproxen increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• modafinil

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

• moexipril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• morphine

  Monitor Closely (2)diphenhydramine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and morphine both increase sedation. Use Caution/Monitor.

• motherwort

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

• moxifloxacin

  Monitor Closely (1)moxifloxacin, naproxen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

• moxisylyte

  Monitor Closely (1)naproxen decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• moxonidine

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

• mycophenolate

  Monitor Closely (1)naproxen will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

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

• nabumetone

  Monitor Closely (2)nabumetone and naproxen both increase anticoagulation. Use Caution/Monitor.
  
  nabumetone and naproxen both increase serum potassium. Use Caution/Monitor.Minor (1)nabumetone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (2)naproxen decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nadolol and naproxen both increase serum potassium. Use Caution/Monitor.

• nalbuphine

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

• nebivolol

  Monitor Closely (3)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

  Monitor Closely (1)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.

• neomycin PO

  Minor (1)naproxen increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• neostigmine

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

• nettle

  Monitor Closely (1)naproxen increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)nettle increases effects of diphenhydramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nitazoxanide

  Minor (2)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

  Minor (1)naproxen and noni juice both increase serum potassium. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (2)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

  Monitor Closely (3)diphenhydramine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both increase sedation. Use Caution/Monitor.

• ofloxacin

  Minor (1)ofloxacin, naproxen. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

• olanzapine

  Monitor Closely (4)diphenhydramine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  olanzapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)diphenhydramine will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• olmesartan

  Monitor Closely (3)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.
  
  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 and naproxen both increase serum potassium. Use Caution/Monitor.

• olopatadine intranasal

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

• onabotulinumtoxinA

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

• opium tincture

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

• orphenadrine

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

• ospemifene

  Monitor Closely (2)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

  Monitor Closely (2)naproxen and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and oxaprozin both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxazepam

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

  Monitor Closely (2)diphenhydramine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymorphone

  Monitor Closely (2)diphenhydramine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  Monitor Closely (4)diphenhydramine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  paliperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and paliperidone both increase sedation. Use Caution/Monitor.

• panax ginseng

  Monitor Closely (1)naproxen and panax ginseng both increase anticoagulation. Use Caution/Monitor.

• pancuronium

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

• papaveretum

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

• papaverine

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

• parecoxib

  Monitor Closely (2)naproxen and parecoxib both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and parecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  Minor (1)naproxen increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• paroxetine

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

• passion flower

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

• pau d'arco

  Monitor Closely (1)naproxen and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• pegaspargase

  Monitor Closely (1)pegaspargase increases effects of naproxen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• peginterferon alfa 2b

  Monitor Closely (1)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.

• pemetrexed

  Serious - Use Alternative (1)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.

• penbutolol

  Monitor Closely (2)naproxen decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  penbutolol and naproxen both increase serum potassium. Use Caution/Monitor.

• pentazocine

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

• pentobarbital

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

• perampanel

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

• perhexiline

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

• perindopril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• perphenazine

  Monitor Closely (4)diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• phendimetrazine

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

• phenelzine

  Monitor Closely (1)phenelzine increases effects of diphenhydramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenindione

  Monitor Closely (1)phenindione and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• phenobarbital

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

• phenoxybenzamine

  Monitor Closely (1)naproxen decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phentermine

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

• phentolamine

  Monitor Closely (1)naproxen decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• phenylephrine

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

• phenylephrine PO

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

• pholcodine

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

• physostigmine

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

• phytoestrogens

  Monitor Closely (1)naproxen and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

• pilocarpine

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

• pimozide

  Monitor Closely (4)diphenhydramine decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pimozide increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and pimozide both increase sedation. Use Caution/Monitor.

• pindolol

  Monitor Closely (2)naproxen decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  pindolol and naproxen both increase serum potassium. Use Caution/Monitor.

• pirbuterol

  Monitor Closely (2)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

  Monitor Closely (2)naproxen and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and piroxicam both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pitolisant

  Serious - Use Alternative (1)diphenhydramine decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

• pivmecillinam

  Monitor Closely (2)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

  Monitor Closely (1)naproxen and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)naproxen and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)naproxen and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium iodide

  Monitor Closely (1)potassium iodide and naproxen both increase serum potassium. Use Caution/Monitor.

• pralatrexate

  Monitor Closely (1)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.

• pralidoxime

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

• pramlintide

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

• prasugrel

  Monitor Closely (1)naproxen, prasugrel. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Chronic use of NSAIDs with prasugrel may increase bleeding risk.

• prazosin

  Monitor Closely (1)naproxen decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  Monitor Closely (1)naproxen, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• prednisone

  Monitor Closely (1)naproxen, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

• pregabalin

  Monitor Closely (1)pregabalin, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primidone

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

• probenecid

  Monitor Closely (1)naproxen will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (4)diphenhydramine decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  prochlorperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and prochlorperazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

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

• promethazine

  Monitor Closely (4)diphenhydramine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and promethazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• propafenone

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

• propantheline

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

• propofol

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

• propranolol

  Monitor Closely (3)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

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

• protamine

  Monitor Closely (1)protamine and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

• protriptyline

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

• pyridostigmine

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

• quazepam

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

• quetiapine

  Monitor Closely (4)diphenhydramine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  quetiapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and quetiapine both increase sedation. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)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.Serious - Use Alternative (1)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

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

• ramelteon

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

• ramipril

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• rapacuronium

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

• reishi

  Monitor Closely (1)naproxen and reishi both increase anticoagulation. Use Caution/Monitor.

• reteplase

  Monitor Closely (1)naproxen and reteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• risperidone

  Monitor Closely (4)diphenhydramine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  risperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and risperidone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rivaroxaban

  Monitor Closely (1)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

  Monitor Closely (1)rivastigmine increases toxicity of naproxen by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

• rocuronium

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

• rose hips

  Minor (1)rose hips will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sacubitril/valsartan

  Monitor Closely (3)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.
  
  sacubitril/valsartan and naproxen both increase serum potassium. Use Caution/Monitor.

• sage

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

• salicylates (non-asa)

  Monitor Closely (2)naproxen and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)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

  Monitor Closely (2)naproxen and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and salsalate both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• saw palmetto

  Monitor Closely (1)saw palmetto increases toxicity of naproxen by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

• scopolamine

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

• scullcap

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

• secobarbital

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

• sertraline

  Monitor Closely (1)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.

• sevoflurane

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

• shepherd's purse

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

• Siberian ginseng

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

• silodosin

  Monitor Closely (1)naproxen decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sodium oxybate

  Serious - Use Alternative (1)diphenhydramine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

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

• sotalol

  Monitor Closely (2)naproxen decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  sotalol and naproxen both increase serum potassium. Use Caution/Monitor.

• sparsentan

  Monitor Closely (1)naproxen and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.

• spironolactone

  Monitor Closely (1)spironolactone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.

• stiripentol

  Monitor Closely (1)stiripentol, diphenhydramine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• streptomycin

  Minor (1)naproxen increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• succinylcholine

  Monitor Closely (2)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

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

• sulfasalazine

  Monitor Closely (2)naproxen and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and sulfasalazine both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)naproxen and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and sulindac both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tacrolimus

  Serious - Use Alternative (1)naproxen, tacrolimus. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant administration increases risk of nephrotoxicity.

• tafluprost

  Monitor Closely (1)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

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

• tamsulosin

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

• tapentadol

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

• telmisartan

  Monitor Closely (3)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.
  
  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 and naproxen both increase serum potassium. Use Caution/Monitor.

• temazepam

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

• temocillin

  Monitor Closely (2)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

  Monitor Closely (1)naproxen and tenecteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

• tenofovir DF

  Monitor Closely (1)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

  Monitor Closely (1)naproxen decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• terbutaline

  Monitor Closely (2)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

  Monitor Closely (4)diphenhydramine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thioridazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)diphenhydramine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  Monitor Closely (4)diphenhydramine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thiothixene increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and thiothixene both increase sedation. Use Caution/Monitor.

• ticarcillin

  Monitor Closely (2)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.

• timolol

  Monitor Closely (3)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

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

• tobramycin

  Minor (1)naproxen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• tobramycin inhaled

  Monitor Closely (1)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

  Monitor Closely (1)naproxen increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolbutamide

  Monitor Closely (1)naproxen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

• tolfenamic acid

  Monitor Closely (2)naproxen and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and tolfenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (2)naproxen and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  naproxen and tolmetin both increase serum potassium. Use Caution/Monitor.Minor (1)naproxen will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolterodine

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

• tolvaptan

  Monitor Closely (1)naproxen and tolvaptan both increase serum potassium. Use Caution/Monitor.

• topiramate

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

• torsemide

  Monitor Closely (1)naproxen increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  Monitor Closely (3)diphenhydramine decreases effects of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.
  
  diphenhydramine and tramadol both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases effects of tramadol by decreasing metabolism. Use Caution/Monitor. Decreased conversion of tramadol to active metabolite.

• trandolapril

  Monitor Closely (1)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.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)tranylcypromine increases effects of diphenhydramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• travoprost ophthalmic

  Monitor Closely (1)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

  Monitor Closely (2)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.Minor (1)diphenhydramine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)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. .

• triamterene

  Monitor Closely (1)triamterene and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.Minor (2)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.

• triazolam

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

• triclofos

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

• trifluoperazine

  Monitor Closely (4)diphenhydramine decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trifluoperazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and trifluoperazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trihexyphenidyl

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

• trimipramine

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

• triprolidine

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

• tropisetron

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

• trospium chloride

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

• valerian

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

• valganciclovir

  Minor (1)naproxen will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valsartan

  Monitor Closely (3)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 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 and naproxen both increase serum potassium. Use Caution/Monitor.

• vancomycin

  Minor (1)naproxen increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• vecuronium

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

• venlafaxine

  Monitor Closely (1)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)

  Monitor Closely (1)naproxen increases and vitamin K1 (phytonadione) decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• voclosporin

  Monitor Closely (1)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

  Monitor Closely (1)naproxen, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• vortioxetine

  Monitor Closely (1)naproxen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

• warfarin

  Monitor Closely (1)naproxen, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Drugs with antiplatelet properties may increase anticoagulation effect of warfarin.

• willow bark

  Minor (1)naproxen will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• xylometazoline

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

• yohimbine

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

• zanubrutinib

  Monitor Closely (1)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

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

• ziprasidone

  Monitor Closely (4)diphenhydramine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  ziprasidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and ziprasidone both increase sedation. Use Caution/Monitor.

• zotepine

  Monitor Closely (4)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.