orphenadrine/aspirin/caffeine (Rx)

Brand and Other Names:Orphengesic Forte
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

orphenadrine/aspirin/caffeine

tablet

  • 50mg/770mg/60mg

Musculoskeletal Pain

Indicated for symptomatic relief of mild-to-moderate pain caused by acute musculoskeletal disorders as an adjunct to rest, physical therapy, and other measures

0.5-1 tablet (25mg/385mg/30mg to 50mg/770mg/60mg) PO TID/QID

Dosage Forms & Strengths

orphenadrine/aspirin/caffeine

tablet

  • 50mg/770mg/60mg

Musculoskeletal Pain

Indicated for symptomatic relief of mild-to-moderate pain caused by acute musculoskeletal disorders as an adjunct to rest, physical therapy, and other measures

<12 years: Safety and efficacy not established

≥12 years: 0.5-1 tablet (25mg/385mg/30mg to 50mg/770mg/60mg) PO TID/QID

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Interactions

Interaction Checker

and orphenadrine/aspirin/caffeine

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            Contraindicated (5)

            • 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.

            • isocarboxazid

              isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • linezolid

              linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            • mifepristone

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

            • phenelzine

              phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

            Serious - Use Alternative (38)

            • abametapir

              abametapir will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

            • 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.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, orphenadrine. Either increases toxicity 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.

            • bupropion

              caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • calcium/magnesium/potassium/sodium oxybates

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

            • captopril

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

            • clonidine

              clonidine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

            • dipyridamole

              caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.

            • 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.

            • fedratinib

              orphenadrine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • 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.

            • givosiran

              givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

            • glucagon

              glucagon increases toxicity of orphenadrine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • glucagon intranasal

              glucagon intranasal increases toxicity of orphenadrine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • hydrocodone

              hydrocodone, orphenadrine. Either increases toxicity 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.

            • 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.

            • iobenguane I 131

              caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • 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

              orphenadrine 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.

            • 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

              orphenadrine, 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.

            • ozanimod

              ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • 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.

            • 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.

            • quinapril

              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.

            • ramipril

              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.

            • regadenoson

              caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

            • sodium oxybate

              orphenadrine, 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.

            Monitor Closely (543)

            • 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.

            • abobotulinumtoxinA

              orphenadrine increases effects of abobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Muscle relaxants may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

              abobotulinumtoxinA increases effects of orphenadrine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

            • 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

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

            • agrimony

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

            • albuterol

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

              albuterol and caffeine both decrease sedation. Use Caution/Monitor.

            • alfalfa

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

            • alfentanil

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

            • alfentanil

              orphenadrine 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

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

              alprazolam and orphenadrine 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.

            • amitriptyline

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

            • American ginseng

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

            • amiloride

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

            • amitriptyline

              amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

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

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

            • amoxapine

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

              amoxapine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine 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.

            • arformoterol

              arformoterol and caffeine both decrease sedation. 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 orphenadrine 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.

            • 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

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

            • arformoterol

              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

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

              orphenadrine and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              armodafinil and caffeine both decrease sedation. Use Caution/Monitor.

            • asenapine

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

            • atenolol

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

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

            • atracurium

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

            • atropine

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

            • atropine IV/IM

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

            • avapritinib

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

            • axitinib

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

            • azelastine

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

              azelastine and orphenadrine 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. .

            • belladonna and opium

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

            • 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

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

            • belladonna alkaloids

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

            • belladonna and opium

              belladonna and opium and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine 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

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

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

            • benzphetamine

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

              caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.

            • benztropine

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

            • brompheniramine

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

            • 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 orphenadrine 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, orphenadrine. Either increases toxicity of the other by 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.

            • brompheniramine

              brompheniramine and orphenadrine 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.

            • buprenorphine

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

            • buprenorphine buccal

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

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

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection increases effects of orphenadrine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • butabarbital

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

            • butabarbital

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

            • butalbital

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

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

            • butorphanol

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

              butorphanol 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.

            • carbinoxamine

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

            • caplacizumab

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

            • captopril

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

            • carbachol

              carbachol increases and orphenadrine 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 orphenadrine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and orphenadrine 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.

            • celecoxib

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

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

            • chloral hydrate

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

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

            • chlordiazepoxide

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

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

            • chlorothiazide

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

            • chlorpheniramine

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

            • chlorpheniramine

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

            • chlorpromazine

              orphenadrine and chlorpromazine both increase sedation. Use Caution/Monitor.

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

            • chlorpropamide

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

            • cinnarizine

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

            • chlorthalidone

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

            • chlorzoxazone

              chlorzoxazone and orphenadrine 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 orphenadrine 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.

              ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.

            • cisatracurium

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

            • clemastine

              clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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 orphenadrine both increase sedation. Use Caution/Monitor.

            • clobetasone

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

            • clomipramine

              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.

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

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

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

            • clonazepam

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

              clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

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

            • clorazepate

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

            • clozapine

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

              orphenadrine and clozapine both increase sedation. Use Caution/Monitor.

            • codeine

              orphenadrine and codeine both increase sedation. Use Caution/Monitor.

              codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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).

            • cyclizine

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

            • 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 orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              cyclizine and orphenadrine both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

              cyproheptadine and orphenadrine 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

            • deferasirox

              deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • 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

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

            • darifenacin

              darifenacin and orphenadrine 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.

            • desipramine

              desipramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and desipramine both increase sedation. Use Caution/Monitor.

              desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

            • dexchlorpheniramine

              dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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 orphenadrine both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

              caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.

            • dextromoramide

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

            • dextroamphetamine

              caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.

            • dextromoramide

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

            • diamorphine

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

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

            • diazepam

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

            • diethylpropion

              caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.

            • 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 orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • difenoxin hcl

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

              orphenadrine 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.

            • dimenhydrinate

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

            • digoxin

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

            • dimenhydrinate

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

            • diphenhydramine

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

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

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

            • diphenoxylate hcl

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

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

            • dipipanone

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

              dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

              dobutamine and caffeine both decrease sedation. Use Caution/Monitor.

            • dobutamine

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

            • donepezil

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

            • dong quai

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

            • dopamine

              caffeine and dopamine both decrease sedation. Use Caution/Monitor.

            • dopexamine

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

              dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

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

            • dosulepin

              orphenadrine and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

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

            • doxazosin

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

            • doxepin

              doxepin and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and doxepin both increase sedation. Use Caution/Monitor.

            • doxylamine

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

            • droperidol

              orphenadrine and droperidol both increase sedation. Use Caution/Monitor.

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

            • drospirenone

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

            • droxidopa

              caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

            • 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.

            • echothiophate iodide

              echothiophate iodide increases and orphenadrine 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.

            • 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.

              ephedrine and caffeine both decrease sedation. Use Caution/Monitor.

            • epinephrine

              epinephrine and caffeine both decrease sedation. Use Caution/Monitor.

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

            • epinephrine inhaled

              caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • epinephrine racemic

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

            • epinephrine racemic

              epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

            • epoprostenol

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

            • 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.

            • esketamine intranasal

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

              esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

            • 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

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

            • estazolam

              estazolam and orphenadrine 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

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

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

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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 orphenadrine both increase sedation. Use Caution/Monitor.

            • fenbufen

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

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

            • fenfluramine

              caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.

              orphenadrine 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.

            • fexinidazole

              fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • fenoprofen

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

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

            • fesoterodine

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

            • feverfew

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

            • finerenone

              orphenadrine 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 weak 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

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

            • flibanserin

              orphenadrine 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.

            • 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

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

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

            • flurazepam

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

              flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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 will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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

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

              formoterol and caffeine both decrease sedation. Use Caution/Monitor.

            • forskolin

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

            • green tea

              green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.

            • 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.

            • galantamine

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

            • garlic

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

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glimepiride

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

            • glipizide

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

            • glyburide

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

            • glycopyrrolate

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

            • glycopyrrolate inhaled

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

            • 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.

            • guselkumab

              guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • haloperidol

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

              orphenadrine and haloperidol both increase sedation. 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.

            • hydromorphone

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

            • homatropine

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

            • horse chestnut seed

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

            • huperzine A

              huperzine A increases and orphenadrine 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.

            • hydralazine

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

            • 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

              orphenadrine and hydromorphone both increase sedation. Use Caution/Monitor.

            • hydroxyzine

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

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

            • hyoscyamine

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

            • iloperidone

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

            • hyoscyamine spray

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

            • ibrutinib

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

            • ibuprofen

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

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

            • ibuprofen IV

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

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

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

            • icosapent

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

            • iloperidone

              orphenadrine and iloperidone both increase sedation. Use Caution/Monitor.

            • 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

              orphenadrine and imipramine both increase sedation. Use Caution/Monitor.

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

              imipramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • incobotulinumtoxinA

              orphenadrine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Muscle relaxants may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

            • isoproterenol

              isoproterenol and caffeine both decrease 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

              ipratropium and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • 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.

            • isoproterenol

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

            • ivacaftor

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

            • ketamine

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

            • ketoprofen

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

              aspirin and ketoprofen both increase serum potassium. 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

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

              ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

            • letermovir

              letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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

              orphenadrine 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.

            • levalbuterol

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

              levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.

            • 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

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

            • levorphanol

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

            • levothyroxine

              caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. COFFEE binds levothyroxine in the GI tract. Separate by 2 hours.

            • lisdexamfetamine

              caffeine and lisdexamfetamine both decrease sedation. 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.

            • lofepramine

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

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

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

            • lofexidine

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

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

            • lomitapide

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

            • loprazolam

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

            • loprazolam

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

            • lorazepam

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

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

            • lormetazepam

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

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

            • lornoxicam

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

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

            • loxapine

              loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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 inhaled

              orphenadrine and loxapine inhaled both increase sedation. Use Caution/Monitor.

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

            • lurasidone

              lurasidone, orphenadrine. 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

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

            • maprotiline

              maprotiline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and maprotiline both increase sedation. Use Caution/Monitor.

            • marijuana

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

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

            • meclizine

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

            • melatonin

              melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

              orphenadrine 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

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

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

            • meprobamate

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

              orphenadrine 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

              metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.

            • metaproterenol

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

            • metaxalone

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

            • methadone

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

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

            • methamphetamine

              caffeine and methamphetamine both decrease 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.

            • methocarbamol

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

            • methotrexate

              caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.

            • methscopolamine

              methscopolamine and orphenadrine 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

              caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.

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

            • methylphenidate

              caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

            • 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.

            • midazolam

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

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

            • midazolam intranasal

              orphenadrine 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.

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

            • midodrine

              caffeine and midodrine both decrease sedation. Use Caution/Monitor.

            • 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.

            • mirtazapine

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

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

            • mistletoe

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

            • modafinil

              caffeine and modafinil both decrease sedation. 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

              orphenadrine and morphine both increase sedation. Use Caution/Monitor.

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

            • motherwort

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

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

            • moxisylyte

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

            • moxonidine

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

            • moxonidine

              orphenadrine 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

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

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

            • nabumetone

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

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

            • nalbuphine

              nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

              orphenadrine 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.

            • 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 orphenadrine 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

              norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.

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

            • nortriptyline

              nortriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and nortriptyline both increase sedation. Use Caution/Monitor.

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

            • olanzapine

              orphenadrine and olanzapine both increase sedation. Use Caution/Monitor.

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

            • oliceridine

              oliceridine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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.

              orphenadrine increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

            • opium tincture

              opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

            • 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 orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • opium tincture

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

            • ospemifene

              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.

            • oxaprozin

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

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

            • oxazepam

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

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

            • oxybutynin

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

            • oxycodone

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

            • oxybutynin topical

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

            • oxybutynin transdermal

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

            • oxycodone

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

            • oxymorphone

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

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

            • paliperidone

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

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

            • panax ginseng

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

            • papaveretum

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

            • pancuronium

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

            • papaveretum

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

            • papaverine

              orphenadrine 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.

            • pau d'arco

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

            • pefloxacin

              pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. 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

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

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

            • pentobarbital

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

              pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

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

            • perphenazine

              orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.

            • phenindione

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

            • phenobarbital

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

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

            • phenoxybenzamine

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

            • phentermine

              caffeine and phentermine both decrease sedation. Use Caution/Monitor.

            • phentolamine

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

            • phenylephrine

              caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

            • phenylephrine PO

              caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.

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

            • pholcodine

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

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

            • physostigmine

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

            • pimozide

              pimozide increases and caffeine decreases sedation. 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 orphenadrine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pilocarpine ophthalmic

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

            • pimozide

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

            • 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.

              pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.

            • piroxicam

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

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

            • primidone

              primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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.

            • prabotulinumtoxinA

              orphenadrine increases effects of prabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Muscle relaxants may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

            • pralidoxime

              pralidoxime and orphenadrine both decrease cholinergic effects/transmission. 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.

            • primidone

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

            • prochlorperazine

              orphenadrine and prochlorperazine both increase sedation. Use Caution/Monitor.

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

            • promethazine

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

              promethazine and orphenadrine both increase sedation. Use Caution/Monitor.

            • propantheline

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

            • propylhexedrine

              caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.

            • propofol

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

            • propranolol

              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

              orphenadrine 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

              protriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and protriptyline both increase sedation. Use Caution/Monitor.

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

            • pyridostigmine

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

            • quazepam

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

            • quazepam

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

            • quetiapine

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

              orphenadrine and quetiapine both increase sedation. Use Caution/Monitor.

            • 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.

            • rasagiline

              rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

            • ramelteon

              orphenadrine 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

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

            • reishi

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

            • remimazolam

              remimazolam, orphenadrine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • 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

              orphenadrine and risperidone both increase sedation. Use Caution/Monitor.

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

            • 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.

            • rucaparib

              rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.

            • rivastigmine

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

            • rocuronium

              rocuronium and orphenadrine 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

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

              salmeterol and caffeine both decrease sedation. Use Caution/Monitor.

            • salsalate

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

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

            • scullcap

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

            • saw palmetto

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

            • scopolamine

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

            • scullcap

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

            • secobarbital

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

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

            • selegiline

              selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

            • 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.

            • shepherd's purse

              shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              orphenadrine 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.

            • solriamfetol

              caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • 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

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

            • sotalol

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

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

            • spironolactone

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

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

            • stiripentol

              stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

              stiripentol, orphenadrine. 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 orphenadrine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sufentanil

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

            • sufentanil

              orphenadrine 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).

            • tapentadol

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

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

            • tazemetostat

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

            • temazepam

              temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. 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

              temazepam and orphenadrine 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

              terbutaline and caffeine both decrease sedation. Use Caution/Monitor.

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

            • teriflunomide

              teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • thioridazine

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

            • thioridazine

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

            • thiothixene

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

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

            • 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.

            • topiramate

              topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • 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.

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

            • tinidazole

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

            • tiotropium

              tiotropium and orphenadrine 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

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

            • tolvaptan

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

            • topiramate

              orphenadrine 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

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

              orphenadrine and tramadol both increase sedation. Use Caution/Monitor.

            • 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.

            • trazodone

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

            • 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

              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.

              trazodone and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • 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

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

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

            • triamterene

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

            • triclofos

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

            • triclofos

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

            • trifluoperazine

              orphenadrine and trifluoperazine both increase sedation. Use Caution/Monitor.

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

            • trihexyphenidyl

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

            • trimipramine

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

            • trimipramine

              trimipramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

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

            • trospium chloride

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

            • 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

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

            • venlafaxine

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

            • voclosporin

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

            • vorapaxar

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

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

            • vortioxetine

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

            • warfarin

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

            • xylometazoline

              caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

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

            • yohimbine

              caffeine and yohimbine both decrease sedation. 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

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

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

            • ziprasidone

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

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

            • zotepine

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

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

            Minor (131)

            • 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.

            • acyclovir

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

            • adenosine

              caffeine decreases effects of adenosine by pharmacodynamic antagonism. 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).

            • amantadine

              amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

            • American ginseng

              American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

            • 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.

            • amobarbital

              amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • anamu

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

            • armodafinil

              armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

            • balsalazide

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

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of 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.

            • bumetanide

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

            • butabarbital

              butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • calcium acetate

              caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

            • 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).

              caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.

            • calcium chloride

              caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

            • cefadroxil

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

            • calcium citrate

              caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

            • calcium gluconate

              caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

            • carbamazepine

              carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • cefamandole

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

            • cefepime

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

            • cefixime

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

            • cefpirome

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

            • cefprozil

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

            • ceftazidime

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

            • ceftibuten

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

            • celecoxib

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

            • cephalexin

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

            • chlorothiazide

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

            • chlorpromazine

              orphenadrine decreases levels of chlorpromazine by unknown mechanism. Minor/Significance Unknown. Excessive anticholinergic effects and/or hypoglycemia possible.

            • 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.

            • 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.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • clotrimazole

              clotrimazole increases levels of caffeine by decreasing metabolism. 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.

            • danshen

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

            • deflazacort

              deflazacort decreases levels of aspirin by increasing renal clearance. 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.

            • 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.

            • eplerenone

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

            • erythromycin base

              erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • ethanol

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

            • etodolac

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

            • eucalyptus

              eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

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

            • fenbufen

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

            • fluconazole

              fluconazole increases levels of caffeine by decreasing metabolism. 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.

            • 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.

            • 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.

            • furosemide

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

            • 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.

            • grapefruit

              grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • guarana

              guarana increases effects of caffeine by pharmacodynamic synergism. 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 will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • itraconazole

              itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • ketoconazole

              ketoconazole increases levels of caffeine by decreasing metabolism. 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.

            • 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.

            • 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.

            • metolazone

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

            • mexiletine

              mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • miconazole vaginal

              miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

            • modafinil

              modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

            • 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.

            • 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.

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

            • pentobarbital

              pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • pipemidic acid

              pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • 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.

            • posaconazole

              posaconazole increases levels of caffeine by decreasing metabolism. 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 will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • rifampin

              rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 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.

            • ruxolitinib

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

            • sage

              sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

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

            • 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.

            • secobarbital

              secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • smoking

              smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            Tachycardia

            Palpitation

            Urinary hesitancy or retention

            Dry mouth

            Blurred vision

            Dilated pupils

            Increased intraocular tension

            Weakness

            Nausea

            Vomiting

            Headache

            Dizziness

            Constipation

            Drowsiness

            Urticaria (rare)

            Other dermatosis (rare)

            Confusion in elderly individuals (infrequent)

            Mild central excitation and occasional hallucinations

            Aplastic anemia (single case)

            Gastrointestinal hemorrhage (rare)

            Transient episodes of light-headedness, dizziness, or syncope

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            Warnings

            Contraindications

            Glaucoma

            Pyloric or duodenal obstruction

            Achalasia

            Prostatic hypertrophy or bladder neck obstructions

            Myasthenia gravis

            Hypersensitivity to orphenadrine, aspirin, or caffeine

            Cautions

            Not recommended for use in patients with chicken pox, influenza, or flu symptoms; Reye syndrome may develop in individuals who have chicken pox, influenza, or flu symptoms; studies suggest association between Reye syndrome and use of medicines containing salicylate or aspirin

            May impair patient’s ability to engage in potentially hazardous activities (eg, operating machinery, driving a motor vehicle)

            Aspirin should be used with extreme caution in the presence of peptic ulcers and coagulation abnormalities

            Safety of continuous long term therapy has not been established; therefore, if prescribed for prolonged use, periodic monitoring recommended of blood, urine, and liver function values

            Mild adverse effects may respond to dose reduction

            Drug reaction with eosinophilia and systemic symptoms

            • Drug Reaction reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
            • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
            • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
            • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately
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            Pregnancy & Lactation

            Pregnancy

            Use of NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment

            Because of these risks, limit dose and duration of drug combination between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy

            Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment

            If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit use to the lowest effective dose and shortest duration possible; if drug combination treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue drug use and follow up according to clinical practice

            If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue treatment and follow up according to clinical practice

            Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive

            Animal data

            • Based on animal data, prostaglandins have been shown to have important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors such as aspirin, resulted in increased pre-and post-implantation loss
            • Prostaglandins also have been shown to have an important role in fetal kidney development; in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses

            Lactation

            Safety during lactation has not been established

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Orphenadrine: Indirect skeletal muscle relaxant; exact mechanism unknown, but may antagonize N-methyl-D-aspartate (NMDA) receptors

            Aspirin: Inhibits synthesis of prostaglandin by cyclooxygenase; has antiinflammatory and analgesic activity

            Caffeine: Mild, direct stimulant effect of the CNS, heart, and cardiovascular system; stimulates the respiratory center of the medulla

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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store below 30ºC (86ºF)

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.