acetaminophen/aspirin/diphenhydramine (OTC)

Dosage Forms & Strengths

acetaminophen/aspirin/diphenhydramine

caplet

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

Headache

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

2 caplets PO HS prn

Headache

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

<12 years: Safety and efficacy not established

≥12 years: 2 caplets PO HS prn

Contraindicated (4)

• abrocitinib

  abrocitinib and aspirin both increase anticoagulation. Contraindicated. Antiplatelet drugs, except for low-dose aspirin (=81 mg qDay), during the first 3 months of treatment are contraindicated.

• dichlorphenamide

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

• eliglustat

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

• mifepristone

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

Serious - Use Alternative (31)

• benazepril

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

• calcium/magnesium/potassium/sodium oxybates

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

• caplacizumab

  caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• captopril

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

• eluxadoline

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

• enalapril

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

• fosinopril

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

• ibuprofen

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

• ibuprofen IV

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

• isocarboxazid

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

• ketorolac

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

• ketorolac intranasal

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

• lesinurad

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

• lisinopril

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

• lonafarnib

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

• macimorelin

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

• measles, mumps, rubella and varicella vaccine, live

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

• mefloquine

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

• methotrexate

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

• metoclopramide intranasal

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

• mifepristone

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

• mitotane

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

• moexipril

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

• 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

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

• perindopril

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

• pexidartinib

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

• pitolisant

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

• pramlintide

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

• pretomanid

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

• probenecid

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

Monitor Closely (539)

• abciximab

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

• acalabrutinib

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

• acebutolol

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

• aceclofenac

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

• acemetacin

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

• acetazolamide

  acetazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.
  
  acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• aclidinium

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

• acrivastine

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

• agrimony

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

• albuterol

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

• alfalfa

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

• alfentanil

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

• alfuzosin

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

• aliskiren

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

• alprazolam

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

• alteplase

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

• American ginseng

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

• amantadine

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

• amifampridine

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

• amiloride

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

• 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.

• amoxicillin

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

• ampicillin

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

• anagrelide

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

• anticholinergic/sedative combos

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

• antithrombin alfa

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

• antithrombin III

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

• apalutamide

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

• apixaban

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

• apomorphine

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

• arformoterol

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

• argatroban

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

• aripiprazole

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

• armodafinil

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

• asenapine

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

• atenolol

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

• atogepant

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

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• avapritinib

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

• axitinib

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

• azelastine

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

• azficel-T

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

• azilsartan

  aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

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

• belladonna alkaloids

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

• belladonna and opium

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

• bemiparin

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

• benazepril

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

• bendroflumethiazide

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

• benperidol

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

• benzhydrocodone/acetaminophen

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

• benzphetamine

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

• benztropine

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

• betaxolol

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

• bethanechol

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

• betrixaban

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

• bimatoprost

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

• bisoprolol

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

• bivalirudin

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

• brexanolone

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

• brexpiprazole

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

• brimonidine

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

• brinzolamide

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

• brivaracetam

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

• brompheniramine

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

• bumetanide

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

• bupivacaine implant

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• buprenorphine, long-acting injection

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

• busulfan

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

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• candesartan

  candesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• captopril

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

• carbachol

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

• carbenoxolone

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

• carbinoxamine

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

• carisoprodol

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

• carvedilol

  carvedilol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• celecoxib

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

• cenobamate

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

• celiprolol

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

• cevimeline

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

• chloral hydrate

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

• chlordiazepoxide

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

• chlorothiazide

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

• chlorpheniramine

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

• chlorpromazine

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

• chlorpropamide

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

• chlorthalidone

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

• chlorzoxazone

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

• choline magnesium trisalicylate

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

• cilostazol

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

• cinnamon

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

• cinnarizine

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

• ciprofloxacin

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

• cisatracurium

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

• citalopram

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

• clemastine

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

• clobazam

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

• clomipramine

  diphenhydramine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  clomipramine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.
  
  diphenhydramine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clopidogrel

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

• clorazepate

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

• clozapine

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

• codeine

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

• collagenase clostridium histolyticum

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

• cordyceps

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

• cortisone

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

• cyclizine

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

• cyclobenzaprine

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

• cyclopenthiazide

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

• cyproheptadine

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

• dabigatran

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

• dalteparin

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

• dantrolene

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

• dapsone topical

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

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

• defibrotide

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

• deflazacort

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

• desflurane

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

• desipramine

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

• desirudin

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

• deutetrabenazine

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

• dexamethasone

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

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

• diclofenac

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

• dicloxacillin

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

• dicyclomine

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

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• diflunisal

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

• digoxin

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

• dimenhydrinate

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

• diphenoxylate hcl

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

• dipipanone

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

• dipyridamole

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

• dobutamine

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

• donepezil

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

• dong quai

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

• 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

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

• dosulepin

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

• doxazosin

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

• doxepin

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

• doxylamine

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

• droperidol

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

• drospirenone

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

• duloxetine

  duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• echothiophate iodide

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

• edoxaban

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

• eltrombopag

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

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

• enalapril

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

• enoxaparin

  enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI
  
  aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• ephedrine

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

• epinephrine

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

• epinephrine racemic

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

• epoprostenol

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

• esketamine intranasal

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

• eprosartan

  eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• eptifibatide

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

• escitalopram

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

• esmolol

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

• estazolam

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

• ethacrynic acid

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

• ethanol

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

• etodolac

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

• etomidate

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

• exenatide injectable solution

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

• exenatide injectable suspension

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

• fenbufen

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

• fenfluramine

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

• fennel

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

• fenoprofen

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

• fentanyl

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

• fentanyl intranasal

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

• fentanyl iontophoretic transdermal system

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

• fentanyl transdermal

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

• fentanyl transmucosal

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

• fesoterodine

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

• feverfew

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

• finerenone

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

• fish oil

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

• fish oil triglycerides

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

• flavoxate

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

• flecainide

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

• flibanserin

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

• fludrocortisone

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

• imatinib

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

• fluoxetine

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

• fluphenazine

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

• flurazepam

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

• flurbiprofen

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

• fluvoxamine

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

• fondaparinux

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

• formoterol

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

• forskolin

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

• gabapentin

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

• fosinopril

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

• furosemide

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

• gabapentin enacarbil

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

• galantamine

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

• ganaxolone

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

• garlic

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

• gentamicin

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

• ginger

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

• ginkgo biloba

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

• glimepiride

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

• glipizide

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

• glyburide

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

• glycopyrrolate

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

• glycopyrrolate inhaled

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

• glycopyrronium tosylate topical

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

• gotu kola

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

• green tea

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

• griseofulvin

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

• haloperidol

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

• hawthorn

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

• henbane

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

• heparin

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

• homatropine

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

• hops

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

• horse chestnut seed

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

• huperzine A

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

• hyaluronidase

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

• hydralazine

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

• hydrocodone

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

• hydrochlorothiazide

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

• hydrocortisone

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

• hydromorphone

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

• hydroxyzine

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

• hyoscyamine

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

• hyoscyamine spray

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

• ibrutinib

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

• ibuprofen

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

• ibuprofen IV

  aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

• icosapent

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

• iloperidone

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

• imatinib

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

• imipramine

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

• indapamide

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

• indomethacin

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

• insulin aspart

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

• insulin aspart protamine/insulin aspart

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

• insulin degludec

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

• insulin degludec/insulin aspart

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin inhaled

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

• insulin isophane human/insulin regular human

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

• insulin lispro

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

• insulin lispro protamine/insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• ipratropium

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

• irbesartan

  irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• isavuconazonium sulfate

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

• isoniazid

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

• isoproterenol

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

• ivacaftor

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

• kava

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

• ketoprofen

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

• ketamine

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

• ketorolac

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

• ketorolac intranasal

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

• ketotifen, ophthalmic

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

• labetalol

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

• lasmiditan

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

• latanoprost

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

• latanoprostene bunod ophthalmic

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

• lemborexant

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

• levalbuterol

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

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

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

• levodopa

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

• levomilnacipran

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

• levorphanol

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

• lisdexamfetamine

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

• lisinopril

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

• lithium

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

• lixisenatide (DSC)

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

• lofepramine

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

• lofexidine

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

• lomitapide

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

• loprazolam

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

• lorazepam

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

• lormetazepam

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

• lornoxicam

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

• losartan

  losartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• loxapine

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

• loxapine inhaled

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

• lurasidone

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

• maprotiline

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

• marijuana

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

• meclizine

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

• meclofenamate

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

• mefenamic acid

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

• melatonin

  melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.
  
  diphenhydramine and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

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

• meperidine

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

• meprobamate

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

• mesalamine

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

• metaproterenol

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

• metaxalone

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

• methazolamide

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

• methadone

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

• methamphetamine

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

• methocarbamol

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

• methscopolamine

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

• methyclothiazide

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

• methylenedioxymethamphetamine

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

• methylprednisolone

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

• metolazone

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

• metoprolol

  metoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mexiletine

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

• midazolam intranasal

  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• milnacipran

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

• midazolam

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

• midazolam intranasal

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

• midodrine

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

• mipomersen

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

• mirtazapine

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

• mistletoe

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

• modafinil

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

• moexipril

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

• morphine

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

• motherwort

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

• moxisylyte

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

• moxonidine

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

• mycophenolate

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

• nabilone

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

• nabumetone

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

• nadolol

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

• nafcillin

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

• nalbuphine

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

• naproxen

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

• nebivolol

  nebivolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nefazodone

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

• neostigmine

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

• nettle

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

• nitazoxanide

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

• nitroglycerin rectal

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

• nitroglycerin sublingual

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

• norepinephrine

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

• nortriptyline

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

• olmesartan

  olmesartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• olanzapine

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

• oliceridine

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

• omega 3 carboxylic acids

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

• omega 3 fatty acids

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

• onabotulinumtoxinA

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

• opium tincture

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

• orphenadrine

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

• ospemifene

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

• oxacillin

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

• oxazepam

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

• oxaprozin

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymorphone

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

• paliperidone

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

• panax ginseng

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

• pancuronium

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

• papaveretum

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

• papaverine

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

• parecoxib

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

• paroxetine

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

• passion flower

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

• pau d'arco

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

• pegaspargase

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

• penbutolol

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

• penicillin G aqueous

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

• pentazocine

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

• pentobarbital

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

• perampanel

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

• perindopril

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

• perphenazine

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

• phendimetrazine

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

• phenelzine

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

• phenindione

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

• phenobarbital

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

• phenoxybenzamine

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

• phentermine

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

• phentolamine

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

• phenylephrine

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

• phenylephrine PO

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

• pholcodine

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

• physostigmine

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

• phytoestrogens

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

• pilocarpine

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

• pimozide

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

• pindolol

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

• pirbuterol

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

• piroxicam

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

• pralidoxime

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

• pivmecillinam

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

• potassium acid phosphate

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

• potassium chloride

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

• potassium citrate

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

• potassium iodide

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

• prasugrel

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

• prazosin

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

• prednisolone

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

• prednisone

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

• pregabalin

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

• primidone

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

• prochlorperazine

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

• promethazine

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

• propafenone

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

• propantheline

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

• propofol

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

• propranolol

  diphenhydramine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propranolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• propylhexedrine

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

• protamine

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

• protriptyline

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

• pyridostigmine

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

• quazepam

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

• quetiapine

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

• quinapril

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

• ramelteon

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

• ramipril

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

• rapacuronium

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

• reishi

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

• reteplase

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

• risperidone

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

• rivaroxaban

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

• rivastigmine

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

• rocuronium

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

• sacubitril/valsartan

  sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• salicylates (non-asa)

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

• salmeterol

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

• salsalate

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

• scopolamine

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

• saw palmetto

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

• scullcap

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

• secobarbital

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

• selumetinib

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

• sertraline

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

• Siberian ginseng

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

• sevoflurane

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

• shepherd's purse

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

• silodosin

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

• sodium picosulfate/magnesium oxide/anhydrous citric acid

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

• sodium sulfate/?magnesium sulfate/potassium chloride

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

• sodium sulfate/potassium sulfate/magnesium sulfate

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

• solifenacin

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

• sotalol

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

• sparsentan

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

• stiripentol

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

• succinylcholine

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

• sufentanil

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

• sulfamethoxazole

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

• sulfasalazine

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

• sulindac

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

• tafluprost

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

• tamoxifen

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

• tamsulosin

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

• tapentadol

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

• tazemetostat

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

• telmisartan

  telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• temazepam

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

• temocillin

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

• tenecteplase

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

• terazosin

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

• terbutaline

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

• tetracaine

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

• thioridazine

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

• ticagrelor

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

• thiothixene

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

• ticarcillin

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

• timolol

  timolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  diphenhydramine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• tinidazole

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

• tiotropium

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

• tirofiban

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

• tobramycin inhaled

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

• tolazamide

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

• tolbutamide

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

• tolfenamic acid

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

• tolmetin

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

• tolterodine

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

• tolvaptan

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

• topiramate

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

• torsemide

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

• tramadol

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

• trandolapril

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

• travoprost ophthalmic

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

• trazodone

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

• triamcinolone acetonide injectable suspension

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

• triazolam

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

• triamterene

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimipramine

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

• triprolidine

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

• trospium chloride

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

• valerian

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

• valproic acid

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

• valsartan

  valsartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• vecuronium

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

• venlafaxine

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

• voclosporin

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

• vorapaxar

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

• vortioxetine

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

• warfarin

  aspirin increases effects of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Avoid coadministration of chronic high-dose aspirin. Aspirin's antiplatelet properties may increase anticoagulation effect of warfarin. The need for simultaneous use of low-dose aspirin and warfarin is common for patients with cardiovascular disease. .
  
  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• xylometazoline

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

• yohimbine

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

• zanubrutinib

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

• ziconotide

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

• ziprasidone

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

• zotepine

  aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine and zotepine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.

Minor (195)

• aceclofenac

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

• acemetacin

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

• acetazolamide

  acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  aspirin will decrease the level or effect of acetazolamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acyclovir

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

• albiglutide

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

• alendronate

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

• aluminum hydroxide

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

• amikacin

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

• aminohippurate sodium

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

• anamu

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

• anastrozole

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

• antithrombin alfa

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

• antithrombin III

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

• argatroban

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

• aripiprazole

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

• ascorbic acid

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

• ashwagandha

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

• balsalazide

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

• bemiparin

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

• bendroflumethiazide

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

• bismuth subsalicylate

  bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

• bivalirudin

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

• brimonidine

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

• bumetanide

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

• calcium carbonate

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

• carbamazepine

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

• cefadroxil

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

• cefamandole

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

• cefepime

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

• cefixime

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

• cefpirome

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

• cefprozil

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

• ceftazidime

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

• ceftibuten

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

• celecoxib

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

• cephalexin

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

• ceritinib

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

• chlorothiazide

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

• chlorpromazine

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

• chlorpropamide

  aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chlorthalidone

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

• cholestyramine

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

• choline magnesium trisalicylate

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

• chromium

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

• clonazepam

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

• colestipol

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

• cortisone

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

• creatine

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

• cyanocobalamin

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

• cyclopenthiazide

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

• cyclophosphamide

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

• dalteparin

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

• danshen

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

• deflazacort

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

• desipramine

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

• devil's claw

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

• dexamethasone

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

• dexfenfluramine

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

• dextroamphetamine

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

• dextromethorphan

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

• diazepam

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

• diclofenac

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

• diclofenac topical

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

• diflunisal

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

• diltiazem

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

• dimenhydrinate

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

• disulfiram

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

• donepezil

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

• doxepin

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

• encainide

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

• enoxaparin

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

• eplerenone

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

• ethanol

  ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

• ethosuximide

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

• etodolac

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

• eucalyptus

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

• felbamate

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

• fenbufen

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

• fenoprofen

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

• fesoterodine

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

• feverfew

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

• fludrocortisone

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

• fluoxetine

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

• fluphenazine

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

• flurbiprofen

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

• folic acid

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

• fondaparinux

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

• fosphenytoin

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

• furosemide

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

• galantamine

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

• ganciclovir

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

• gentamicin

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

• glimepiride

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

• glipizide

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

• glyburide

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

• green tea

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

• heparin

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

• hydrochlorothiazide

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

• hydrocortisone

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

• ibuprofen

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

• imidapril

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

• indapamide

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

• indomethacin

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

• isoniazid

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

• ketoprofen

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

• ketorolac

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

• ketorolac intranasal

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

• L-methylfolate

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

• lacosamide

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

• lamotrigine

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

• larotrectinib

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

• levetiracetam

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

• levoketoconazole

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

• liraglutide

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

• loratadine

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

• lorazepam

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

• lornoxicam

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

• meclofenamate

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

• mefenamic acid

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

• meloxicam

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

• mesalamine

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

• methsuximide

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

• methyclothiazide

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

• methylprednisolone

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

• metoclopramide

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

• metolazone

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

• metronidazole

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

• nabumetone

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

• naproxen

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

• neomycin PO

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

• nettle

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

• nitazoxanide

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

• noni juice

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

• ofloxacin

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

• oxaprozin

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

• oxcarbazepine

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• parecoxib

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

• paromomycin

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

• paroxetine

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

• penicillin VK

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

• pentazocine

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

• perhexiline

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

• perphenazine

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

• phenindione

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

• phenobarbital

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

• phenytoin

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

• piperacillin

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

• piroxicam

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

• prednisolone

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

• prednisone

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

• primidone

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

• prochlorperazine

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

• promazine

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

• promethazine

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

• protamine

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

• rifabutin

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

• rifampin

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

• risperidone

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

• rose hips

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

• rufinamide

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

• ruxolitinib

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

• ruxolitinib topical

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

• sage

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

• Siberian ginseng

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

• salicylates (non-asa)

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

• salsalate

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

• sodium bicarbonate

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

• sodium citrate/citric acid

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

• stiripentol

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

• streptomycin

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

• sulfadiazine

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

• sulfasalazine

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

• sulfisoxazole

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

• sulindac

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

• teniposide

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

• tiagabine

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

• tiludronate

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

• tobramycin

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

• tolazamide

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

• tolbutamide

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

• tolfenamic acid

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

• tolmetin

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

• tolterodine

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

• topiramate

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

• trazodone

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

• triamcinolone acetonide injectable suspension

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

• triamterene

  triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• trifluoperazine

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

• tropisetron

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

• valganciclovir

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

• valproic acid

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

• abciximab

  Monitor Closely (1)aspirin, abciximab. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• abrocitinib

  Contraindicated (1)abrocitinib and aspirin both increase anticoagulation. Contraindicated. Antiplatelet drugs, except for low-dose aspirin (=81 mg qDay), during the first 3 months of treatment are contraindicated.

• acalabrutinib

  Monitor Closely (1)acalabrutinib increases effects of aspirin by anticoagulation. Modify Therapy/Monitor Closely. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.

• acebutolol

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

• aceclofenac

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

• acemetacin

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

• acetazolamide

  Monitor Closely (2)acetazolamide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).
  
  acetazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.Minor (2)acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  aspirin will decrease the level or effect of acetazolamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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)aspirin will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

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

• albiglutide

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

• albuterol

  Monitor Closely (2)diphenhydramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alendronate

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

• alfalfa

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

• aliskiren

  Monitor Closely (1)aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

• alprazolam

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

• alteplase

  Monitor Closely (1)aspirin, alteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• aluminum hydroxide

  Minor (1)aluminum hydroxide, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• amantadine

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

• American ginseng

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

• amiloride

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

• aminohippurate sodium

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

• 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.

• amoxicillin

  Monitor Closely (2)amoxicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  amoxicillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ampicillin

  Monitor Closely (1)ampicillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• anagrelide

  Monitor Closely (2)aspirin, anagrelide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.
  
  anagrelide, aspirin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; increases risk of bleeding; monitor closely.

• anamu

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

• anastrozole

  Minor (1)aspirin will decrease the level or effect of anastrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 (2)antithrombin alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin alfa. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Minor (1)acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  Monitor Closely (2)antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, antithrombin III. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Minor (1)acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• apalutamide

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

• apixaban

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

• apomorphine

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

• argatroban

  Monitor Closely (2)aspirin, argatroban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  argatroban and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

• aripiprazole

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

• armodafinil

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

• ascorbic acid

  Minor (3)ascorbic acid will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.
  
  ascorbic acid increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

• asenapine

  Monitor Closely (2)asenapine and diphenhydramine both increase sedation. Use Caution/Monitor.
  
  aspirin 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.

• atenolol

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

• atogepant

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

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• avapritinib

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

• axitinib

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

• azelastine

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

• azficel-T

  Monitor Closely (1)azficel-T, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking aspirin may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of aspirin is not recommended. .

• azilsartan

  Monitor Closely (2)aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

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

• balsalazide

  Minor (1)aspirin 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 aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• benazepril

  Monitor Closely (1)benazepril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• bendroflumethiazide

  Monitor Closely (1)aspirin 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 aspirin 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 (2)diphenhydramine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.
  
  benzhydrocodone/acetaminophen and diphenhydramine both increase sedation. Use Caution/Monitor.

• benzphetamine

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

• benztropine

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

• betaxolol

  Monitor Closely (2)aspirin decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  betaxolol and aspirin 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)aspirin, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

• bimatoprost

  Monitor Closely (1)bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• bismuth subsalicylate

  Minor (1)bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

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

• bivalirudin

  Monitor Closely (2)bivalirudin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin, bivalirudin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Minor (1)acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• brexanolone

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

• brexpiprazole

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

• brimonidine

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

• brinzolamide

  Monitor Closely (1)brinzolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• brivaracetam

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

• brompheniramine

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

• bumetanide

  Monitor Closely (2)aspirin decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  aspirin increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

• bupivacaine implant

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• buprenorphine, long-acting injection

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

• busulfan

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

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• calcium carbonate

  Minor (1)calcium carbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

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

• caplacizumab

  Serious - Use Alternative (1)caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• captopril

  Monitor Closely (1)captopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• carbachol

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

• carbamazepine

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

• carbenoxolone

  Monitor Closely (1)aspirin 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)carvedilol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• cefadroxil

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

• cefamandole

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

• cefepime

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

• cefixime

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

• cefpirome

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

• cefprozil

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

• ceftazidime

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

• ceftibuten

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

• celecoxib

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

• celiprolol

  Monitor Closely (2)aspirin decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  celiprolol and aspirin 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 aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceritinib

  Minor (1)aspirin will decrease the level or effect of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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)aspirin 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 aspirin 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)aspirin increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (2)aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chlorthalidone

  Monitor Closely (1)aspirin 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 aspirin 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.

• cholestyramine

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

• choline magnesium trisalicylate

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

• chromium

  Minor (1)aspirin increases levels of chromium by unspecified interaction mechanism. Minor/Significance Unknown.

• cilostazol

  Monitor Closely (1)aspirin, cilostazol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• cinnamon

  Monitor Closely (1)aspirin 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)aspirin decreases levels of ciprofloxacin by Other (see comment). Use Caution/Monitor. Comment: Buffered aspirin may decrease absorption of quinolones. Consider administering 2 hr before or 6 hr after, buffered aspirin administration.

• cisatracurium

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

• citalopram

  Monitor Closely (1)citalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clemastine

  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, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.
  
  diphenhydramine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clopidogrel

  Monitor Closely (1)aspirin, clopidogrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• clorazepate

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

• clozapine

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

• codeine

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

• colestipol

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

• collagenase clostridium histolyticum

  Monitor Closely (1)aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

• cordyceps

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

• cortisone

  Monitor Closely (1)aspirin, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• creatine

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

• cyanocobalamin

  Minor (1)aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (2)cyclizine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and diphenhydramine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)cyclobenzaprine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.

• cyclopenthiazide

  Monitor Closely (1)aspirin 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 aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  Minor (1)aspirin will decrease the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and diphenhydramine both increase sedation. Use Caution/Monitor.

• dabigatran

  Monitor Closely (1)dabigatran and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin

• dalteparin

  Monitor Closely (2)aspirin, dalteparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  dalteparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• danshen

  Minor (1)aspirin and danshen both increase anticoagulation. Minor/Significance Unknown.

• dantrolene

  Monitor Closely (1)diphenhydramine and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone topical

  Monitor Closely (1)acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  Monitor Closely (1)diphenhydramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  Monitor Closely (1)darifenacin and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)deferasirox, aspirin. 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 aspirin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

• deflazacort

  Monitor Closely (1)aspirin, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)deflazacort decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• 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.

• desirudin

  Monitor Closely (1)aspirin, desirudin. Either increases levels of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• deutetrabenazine

  Monitor Closely (1)diphenhydramine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• devil's claw

  Minor (1)aspirin and devil's claw both increase anticoagulation. Minor/Significance Unknown.

• dexamethasone

  Monitor Closely (1)aspirin, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)dexamethasone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (1)diphenhydramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmedetomidine

  Monitor Closely (1)diphenhydramine and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)diphenhydramine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (1)diphenhydramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromethorphan

  Minor (1)diphenhydramine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (1)diphenhydramine and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)diphenhydramine and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diphenhydramine and diazepam both increase sedation. Use Caution/Monitor.Minor (1)diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dichlorphenamide

  Contraindicated (1)dichlorphenamide increases levels of aspirin by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

• diclofenac

  Monitor Closely (2)aspirin and diclofenac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diclofenac both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diclofenac topical

  Minor (1)diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• dicloxacillin

  Monitor Closely (1)dicloxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

• 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)aspirin and diflunisal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and diflunisal both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (1)aspirin and digoxin both increase serum potassium. Use Caution/Monitor.

• diltiazem

  Minor (1)diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• 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.

• dipyridamole

  Monitor Closely (1)aspirin, dipyridamole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (2)diphenhydramine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• donepezil

  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)aspirin 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)aspirin increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  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)aspirin 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 aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• duloxetine

  Monitor Closely (2)duloxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  diphenhydramine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• echothiophate iodide

  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, aspirin. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• eliglustat

  Contraindicated (1)diphenhydramine increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindiated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• eltrombopag

  Monitor Closely (1)eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

• eluxadoline

  Serious - Use Alternative (1)diphenhydramine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• enalapril

  Monitor Closely (1)enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• encainide

  Minor (1)diphenhydramine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• enoxaparin

  Monitor Closely (2)enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI
  
  aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Minor (1)acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• ephedrine

  Monitor Closely (2)aspirin increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (2)aspirin increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (2)diphenhydramine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• eplerenone

  Minor (1)aspirin decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

• epoprostenol

  Monitor Closely (1)aspirin and epoprostenol both increase anticoagulation. Use Caution/Monitor.

• eprosartan

  Monitor Closely (3)aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• eptifibatide

  Monitor Closely (1)aspirin, eptifibatide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• escitalopram

  Monitor Closely (1)escitalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, diphenhydramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  Monitor Closely (2)aspirin decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  esmolol and aspirin 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)aspirin 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.Minor (3)ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.
  
  ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

• ethosuximide

  Minor (1)ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• etodolac

  Monitor Closely (2)aspirin and etodolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and etodolac both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of etodolac 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.

• exenatide injectable solution

  Monitor Closely (1)exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• exenatide injectable suspension

  Monitor Closely (1)exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

• felbamate

  Minor (1)felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• fenbufen

  Monitor Closely (2)aspirin and fenbufen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenbufen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. 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)aspirin and fennel both increase anticoagulation. Use Caution/Monitor.

• fenoprofen

  Monitor Closely (2)aspirin and fenoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and fenoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Monitor Closely (2)fentanyl, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl intranasal

  Monitor Closely (2)fentanyl intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl intranasal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl iontophoretic transdermal system

  Monitor Closely (1)fentanyl iontophoretic transdermal system and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transdermal

  Monitor Closely (2)fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.

• fentanyl transmucosal

  Monitor Closely (1)fentanyl transmucosal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• fesoterodine

  Monitor Closely (1)diphenhydramine and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• feverfew

  Monitor Closely (1)aspirin and feverfew both increase anticoagulation. Use Caution/Monitor.Minor (1)aspirin decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

• finerenone

  Monitor Closely (1)acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

• fish oil

  Monitor Closely (1)fish oil, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• fish oil triglycerides

  Monitor Closely (1)fish oil triglycerides will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flavoxate

  Monitor Closely (1)diphenhydramine and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flecainide

  Monitor Closely (1)diphenhydramine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• flibanserin

  Monitor Closely (2)diphenhydramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

• fludrocortisone

  Monitor Closely (1)aspirin, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)fludrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.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)aspirin and flurbiprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and flurbiprofen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)fluvoxamine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding SSRIs inhib. serotonin uptake by platelets.

• folic acid

  Minor (1)aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fondaparinux

  Monitor Closely (1)fondaparinux and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• formoterol

  Monitor Closely (2)diphenhydramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• forskolin

  Monitor Closely (1)aspirin and forskolin both increase anticoagulation. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)fosinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• fosphenytoin

  Minor (1)fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• furosemide

  Monitor Closely (1)aspirin increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin 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)aspirin will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• garlic

  Monitor Closely (1)aspirin and garlic both increase anticoagulation. Use Caution/Monitor.

• gentamicin

  Monitor Closely (1)aspirin increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• ginger

  Monitor Closely (1)aspirin and ginger both increase anticoagulation. Use Caution/Monitor.

• ginkgo biloba

  Monitor Closely (1)aspirin and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

• glimepiride

  Monitor Closely (1)aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glipizide

  Monitor Closely (1)aspirin increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glyburide

  Monitor Closely (1)aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• 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 increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.Minor (1)green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• griseofulvin

  Monitor Closely (1)griseofulvin decreases levels of aspirin by unknown mechanism. Use Caution/Monitor.

• 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 (2)aspirin, heparin. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  heparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• homatropine

  Monitor Closely (1)diphenhydramine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hops

  Monitor Closely (1)hops increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• horse chestnut seed

  Monitor Closely (1)aspirin 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 (2)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.
  
  aspirin decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  Monitor Closely (1)aspirin decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• hydrochlorothiazide

  Monitor Closely (1)aspirin 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 aspirin 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)aspirin, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• 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 aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen

  Monitor Closely (2)aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (2)ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.
  
  ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.Minor (1)aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (3)aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (2)ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.
  
  ibuprofen IV decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

• icosapent

  Monitor Closely (1)icosapent, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time. Periodically monitor if coadministered with other drugs that affect bleeding.

• 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 (2)imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.
  
  imatinib, aspirin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

• imidapril

  Minor (1)aspirin 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)aspirin 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 aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  Monitor Closely (2)aspirin and indomethacin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and indomethacin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin aspart protamine/insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec

  Monitor Closely (1)aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  Monitor Closely (1)aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

• insulin detemir

  Monitor Closely (1)aspirin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glargine

  Monitor Closely (1)aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glulisine

  Monitor Closely (1)aspirin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  Monitor Closely (1)aspirin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin isophane human/insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro protamine/insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin NPH

  Monitor Closely (1)aspirin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• ipratropium

  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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of 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 aspirin both increase serum potassium. Use Caution/Monitor.

• isavuconazonium sulfate

  Monitor Closely (1)acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid increases effects of diphenhydramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• isoniazid

  Monitor Closely (1)isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.Minor (1)isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (2)diphenhydramine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  aspirin increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ivacaftor

  Monitor Closely (1)acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• kava

  Monitor Closely (1)kava increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (1)ketamine and diphenhydramine both increase sedation. Use Caution/Monitor.

• ketoprofen

  Monitor Closely (2)aspirin and ketoprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketoprofen both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)aspirin and ketorolac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)aspirin, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)aspirin will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)aspirin and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (1)aspirin, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.Minor (1)aspirin will increase the level or effect of ketorolac intranasal 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.

• L-methylfolate

  Minor (1)aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• labetalol

  Monitor Closely (2)aspirin decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  labetalol and aspirin both increase serum potassium. Use Caution/Monitor.

• lacosamide

  Minor (1)lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lamotrigine

  Minor (1)lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• larotrectinib

  Minor (1)aspirin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• latanoprostene bunod ophthalmic

  Monitor Closely (1)latanoprostene bunod ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lemborexant

  Monitor Closely (2)acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
  
  lemborexant, diphenhydramine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lesinurad

  Serious - Use Alternative (1)aspirin decreases effects of lesinurad by unspecified interaction mechanism. Avoid or Use Alternate Drug. Aspirin at doses >325 mg/day may decrease lesinurad efficacy. Aspirin doses 325 mg/day or less (ie, for cardiovascular event prophylaxis) does not decrease lesinurad efficacy and can be coadministered.

• levalbuterol

  Monitor Closely (2)aspirin increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levetiracetam

  Minor (1)levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levodopa

  Monitor Closely (1)diphenhydramine, levodopa. Other (see comment). Use Caution/Monitor. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

• levoketoconazole

  Minor (1)aspirin will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (2)levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
  
  acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

• levorphanol

  Monitor Closely (1)diphenhydramine and levorphanol both increase sedation. Use Caution/Monitor.

• liraglutide

  Minor (1)liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• lisdexamfetamine

  Monitor Closely (1)diphenhydramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lisinopril

  Monitor Closely (1)lisinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lithium

  Monitor Closely (1)aspirin increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

• lofepramine

  Monitor Closely (3)diphenhydramine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  Monitor Closely (1)diphenhydramine and lofexidine both increase sedation. Use Caution/Monitor.

• lomitapide

  Monitor Closely (1)acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loprazolam

  Monitor Closely (1)diphenhydramine and loprazolam both increase sedation. Use Caution/Monitor.

• loratadine

  Minor (1)diphenhydramine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lorazepam

  Monitor Closely (1)diphenhydramine and lorazepam both increase sedation. Use Caution/Monitor.Minor (1)lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lormetazepam

  Monitor Closely (1)diphenhydramine and lormetazepam both increase sedation. Use Caution/Monitor.

• lornoxicam

  Monitor Closely (2)aspirin and lornoxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and lornoxicam both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (3)losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan and aspirin 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.

• macimorelin

  Serious - Use Alternative (1)aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

• 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.

• measles, mumps, rubella and varicella vaccine, live

  Serious - Use Alternative (1)aspirin, measles, mumps, rubella and varicella vaccine, live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• meclizine

  Monitor Closely (1)diphenhydramine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• meclofenamate

  Monitor Closely (2)aspirin and meclofenamate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meclofenamate both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)aspirin and mefenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and mefenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of mefenamic acid 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)melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.
  
  diphenhydramine and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  Monitor Closely (2)aspirin and meloxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and meloxicam both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of meloxicam 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, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.Minor (1)aspirin will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (2)aspirin increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  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.

• methazolamide

  Monitor Closely (1)methazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• methocarbamol

  Monitor Closely (1)diphenhydramine and methocarbamol both increase sedation. Use Caution/Monitor.

• methotrexate

  Serious - Use Alternative (1)aspirin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.

• methscopolamine

  Monitor Closely (1)diphenhydramine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methsuximide

  Minor (1)methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• methyclothiazide

  Monitor Closely (1)aspirin 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 aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• 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)aspirin, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• metoclopramide

  Minor (1)metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)diphenhydramine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)aspirin 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 aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)metoprolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• mexiletine

  Monitor Closely (1)diphenhydramine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam

  Monitor Closely (1)diphenhydramine and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)midazolam intranasal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

• midodrine

  Monitor Closely (1)diphenhydramine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  Contraindicated (1)aspirin, mifepristone. Other (see comment). Contraindicated. Comment: Aspirin induced antiplatelet activity may induce excessive bleeding after an abortion w/mifepristone (RU 486).Serious - Use Alternative (1)aspirin will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• milnacipran

  Monitor Closely (1)milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• mipomersen

  Monitor Closely (1)mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirtazapine

  Monitor Closely (1)diphenhydramine and mirtazapine both increase sedation. Use Caution/Monitor.

• mistletoe

  Monitor Closely (1)aspirin increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mitotane

  Serious - Use Alternative (1)aspirin will decrease the level or effect of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• 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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• 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.

• moxisylyte

  Monitor Closely (1)aspirin 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)aspirin 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)aspirin and nabumetone both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and nabumetone both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (2)aspirin decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nadolol and aspirin both increase serum potassium. Use Caution/Monitor.

• nafcillin

  Monitor Closely (2)nafcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  nafcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)diphenhydramine and nalbuphine both increase sedation. Use Caution/Monitor.

• naproxen

  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.

• nebivolol

  Monitor Closely (3)aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  nebivolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  diphenhydramine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nefazodone

  Monitor Closely (1)nefazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• neomycin PO

  Minor (1)aspirin 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)aspirin 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

  Monitor Closely (1)nitazoxanide, aspirin. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.Minor (1)nitazoxanide, diphenhydramine. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

• nitroglycerin rectal

  Monitor Closely (1)aspirin will increase the level or effect of nitroglycerin rectal by Other (see comment). Use Caution/Monitor. The pharmacological effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

• nitroglycerin sublingual

  Monitor Closely (1)aspirin increases effects of nitroglycerin sublingual by additive vasodilation. Use Caution/Monitor. Vasodilatory and hemodynamic effects of NTG may be enhanced by coadministration with aspirin (additive effect desirable for emergent treatment).

• noni juice

  Minor (1)aspirin and noni juice both increase serum potassium. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (2)aspirin increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  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, aspirin. 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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of 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 aspirin 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.

• omega 3 carboxylic acids

  Monitor Closely (1)omega 3 carboxylic acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

• omega 3 fatty acids

  Monitor Closely (1)omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• onabotulinumtoxinA

  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.
  
  aspirin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxacillin

  Monitor Closely (2)oxacillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  oxacillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• oxaprozin

  Monitor Closely (2)aspirin and oxaprozin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and oxaprozin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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.

• oxcarbazepine

  Minor (1)oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  Monitor Closely (1)diphenhydramine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (1)diphenhydramine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Monitor Closely (1)diphenhydramine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (2)diphenhydramine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymorphone

  Monitor Closely (2)diphenhydramine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and oxymorphone both increase sedation. Use Caution/Monitor.

• paliperidone

  Monitor Closely (4)diphenhydramine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  paliperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and paliperidone both increase sedation. Use Caution/Monitor.

• panax ginseng

  Monitor Closely (1)aspirin 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)aspirin and parecoxib both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and parecoxib both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paromomycin

  Minor (1)aspirin increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• paroxetine

  Monitor Closely (1)paroxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.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)aspirin and pau d'arco both increase anticoagulation. Use Caution/Monitor.

• pegaspargase

  Monitor Closely (1)pegaspargase increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

• pemetrexed

  Serious - Use Alternative (1)aspirin increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

• penbutolol

  Monitor Closely (2)aspirin decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  penbutolol and aspirin both increase serum potassium. Use Caution/Monitor.

• penicillin G aqueous

  Monitor Closely (2)penicillin G aqueous, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  penicillin G aqueous, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• penicillin VK

  Minor (1)penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

• pentazocine

  Monitor Closely (1)diphenhydramine and pentazocine both increase sedation. Use Caution/Monitor.Minor (1)aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

• 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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin,in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• perphenazine

  Monitor Closely (4)diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• pexidartinib

  Serious - Use Alternative (1)acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• phendimetrazine

  Monitor Closely (1)diphenhydramine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Monitor Closely (1)phenelzine increases effects of diphenhydramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenindione

  Monitor Closely (1)phenindione and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

  Monitor Closely (1)diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• phenoxybenzamine

  Monitor Closely (1)aspirin 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)aspirin 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. .

• phenytoin

  Minor (1)phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• pholcodine

  Monitor Closely (1)diphenhydramine and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  Monitor Closely (1)physostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phytoestrogens

  Monitor Closely (1)aspirin 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)aspirin decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  pindolol and aspirin both increase serum potassium. Use Caution/Monitor.

• piperacillin

  Minor (1)piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

• pirbuterol

  Monitor Closely (2)aspirin increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diphenhydramine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• piroxicam

  Monitor Closely (2)aspirin and piroxicam both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and piroxicam both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  pivmecillinam, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• potassium acid phosphate

  Monitor Closely (1)aspirin and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)aspirin and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

• potassium iodide

  Monitor Closely (1)potassium iodide and aspirin both increase serum potassium. Use Caution/Monitor.

• 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)aspirin, prasugrel. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• prazosin

  Monitor Closely (1)aspirin decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• prednisolone

  Monitor Closely (1)aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• prednisone

  Monitor Closely (1)aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (1)pregabalin, diphenhydramine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• pretomanid

  Serious - Use Alternative (1)acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• primidone

  Monitor Closely (1)diphenhydramine and primidone both increase sedation. Use Caution/Monitor.Minor (1)primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• probenecid

  Serious - Use Alternative (1)aspirin decreases effects of probenecid by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Aspirin decreases uricosuric action of probenecid.

• 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)diphenhydramine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propranolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  aspirin decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• propylhexedrine

  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 aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.Minor (1)acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

• protriptyline

  Monitor Closely (2)diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

  Monitor Closely (1)diphenhydramine and quazepam both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (4)diphenhydramine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  quetiapine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and quetiapine both increase sedation. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, 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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, 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)aspirin and reishi both increase anticoagulation. Use Caution/Monitor.

• reteplase

  Monitor Closely (1)aspirin, reteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• rifabutin

  Minor (1)rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  Minor (1)rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• risperidone

  Monitor Closely (4)diphenhydramine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  risperidone increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and risperidone both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rivaroxaban

  Monitor Closely (1)aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• rivastigmine

  Monitor Closely (1)rivastigmine increases toxicity of aspirin 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 (3)rose hips will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.
  
  rose hips increases levels of aspirin by decreasing renal clearance. Minor/Significance Unknown.

• rufinamide

  Minor (1)rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ruxolitinib

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sacubitril/valsartan

  Monitor Closely (3)sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  sacubitril/valsartan and aspirin 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)aspirin and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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.
  
  aspirin increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salsalate

  Monitor Closely (2)aspirin and salsalate both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and salsalate both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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 aspirin 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.

• selumetinib

  Monitor Closely (1)aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

• sertraline

  Monitor Closely (1)sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• 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)aspirin decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

• sodium bicarbonate

  Minor (1)sodium bicarbonate, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• sodium citrate/citric acid

  Minor (1)sodium citrate/citric acid, aspirin. Mechanism: passive renal tubular reabsorption due to increased pH. Minor/Significance Unknown. Salicylate levels increased at moderate doses; salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

• 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)aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• solifenacin

  Monitor Closely (1)diphenhydramine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sotalol

  Monitor Closely (2)aspirin decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.
  
  sotalol and aspirin both increase serum potassium. Use Caution/Monitor.

• sparsentan

  Monitor Closely (1)aspirin 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 (2)aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.
  
  spironolactone and aspirin 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.Minor (1)aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• streptomycin

  Minor (1)aspirin increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

• succinylcholine

  Monitor Closely (2)aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.
  
  succinylcholine increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

  Monitor Closely (1)diphenhydramine and sufentanil both increase sedation. Use Caution/Monitor.

• sulfadiazine

  Minor (1)aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Monitor Closely (1)aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• sulfasalazine

  Monitor Closely (2)aspirin and sulfasalazine both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulfasalazine both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  Minor (1)aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)aspirin and sulindac both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and sulindac both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tafluprost

  Monitor Closely (1)tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tamoxifen

  Monitor Closely (1)diphenhydramine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tamsulosin

  Monitor Closely (1)diphenhydramine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tapentadol

  Monitor Closely (1)diphenhydramine and tapentadol both increase sedation. Use Caution/Monitor.

• tazemetostat

  Monitor Closely (1)acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• telmisartan

  Monitor Closely (3)telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan and aspirin 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, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  temocillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• tenecteplase

  Monitor Closely (1)aspirin, tenecteplase. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• teniposide

  Minor (1)aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

• terazosin

  Monitor Closely (1)aspirin 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.
  
  aspirin increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tetracaine

  Monitor Closely (1)tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  Monitor Closely (4)diphenhydramine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thioridazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)diphenhydramine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• thiothixene

  Monitor Closely (4)diphenhydramine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thiothixene increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and thiothixene both increase sedation. Use Caution/Monitor.

• tiagabine

  Minor (1)tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ticagrelor

  Monitor Closely (1)aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.

• ticarcillin

  Monitor Closely (2)ticarcillin, aspirin. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.
  
  ticarcillin, aspirin. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ticlopidine

  Serious - Use Alternative (1)aspirin increases effects of ticlopidine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced risk of hemorrhage.

• tiludronate

  Minor (1)aspirin decreases levels of tiludronate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• timolol

  Monitor Closely (3)timolol and aspirin both increase serum potassium. Use Caution/Monitor.
  
  diphenhydramine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  aspirin decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

• tinidazole

  Monitor Closely (1)acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tiotropium

  Monitor Closely (1)diphenhydramine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tirofiban

  Monitor Closely (1)aspirin, tirofiban. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• tobramycin

  Minor (1)aspirin 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 aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  Monitor Closely (1)aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolbutamide

  Monitor Closely (1)aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolfenamic acid

  Monitor Closely (2)aspirin and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolfenamic acid both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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)aspirin and tolmetin both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and tolmetin both increase serum potassium. Use Caution/Monitor.Minor (1)aspirin 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)aspirin and tolvaptan both increase serum potassium. Use Caution/Monitor.

• topiramate

  Monitor Closely (1)diphenhydramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• torsemide

  Monitor Closely (1)aspirin 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, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.Serious - Use Alternative (1)aspirin, 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, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  Monitor Closely (2)diphenhydramine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.Minor (1)diphenhydramine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.Minor (1)triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• triamterene

  Monitor Closely (1)triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.Minor (2)triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• 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)aspirin will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valproic acid

  Monitor Closely (1)aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.Minor (1)valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• valsartan

  Monitor Closely (3)valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of 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 aspirin both increase serum potassium. Use Caution/Monitor.

• vancomycin

  Minor (1)aspirin increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

• varicella virus vaccine live

  Serious - Use Alternative (1)aspirin, varicella virus vaccine live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• vecuronium

  Monitor Closely (1)diphenhydramine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• venlafaxine

  Monitor Closely (1)venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• verapamil

  Minor (1)verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• voclosporin

  Monitor Closely (1)voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vorapaxar

  Monitor Closely (2)aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.
  
  aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• vortioxetine

  Monitor Closely (1)aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

• warfarin

  Monitor Closely (2)aspirin increases effects of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Avoid coadministration of chronic high-dose aspirin. Aspirin's antiplatelet properties may increase anticoagulation effect of warfarin. The need for simultaneous use of low-dose aspirin and warfarin is common for patients with cardiovascular disease. .
  
  acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• willow bark

  Minor (2)aspirin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  willow bark increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

• 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.

• zafirlukast

  Minor (1)aspirin increases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

• zanubrutinib

  Monitor Closely (1)aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

• ziconotide

  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.

• zoledronic acid

  Minor (1)aspirin decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• zonisamide

  Minor (1)zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

• zotepine

  Monitor Closely (4)aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  diphenhydramine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine and zotepine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.