orphenadrine/aspirin/caffeine (Rx)

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

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

Contraindicated (5)

• abrocitinib

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

• dichlorphenamide

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

• fezolinetant

  orphenadrine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
  
  caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• isocarboxazid

  isocarboxazid 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).

Serious - Use Alternative (42)

• 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.
  
  benzhydrocodone/acetaminophen and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine subdermal implant

  buprenorphine subdermal implant and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• caplacizumab

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

• captopril

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

• 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.

• olopatadine intranasal

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

• 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 (552)

• 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.

• acrivastine

  acrivastine and orphenadrine both increase sedation. 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.

• amisulpride

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

• 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

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

• asenapine transdermal

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

• atenolol

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

• 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.
  
  avapritinib and orphenadrine both increase sedation. 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.

• brexpiprazole

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

• brimonidine

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

• brinzolamide

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

• brivaracetam

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

• 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.

• 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.

• 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.

• daridorexant

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

• darifenacin

  darifenacin and 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.

• difelikefalin

  difelikefalin and orphenadrine both increase sedation. 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.

• ganaxolone

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

• garlic

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

• gentamicin

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

• ginger

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

• ginkgo biloba

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

• glimepiride

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

• glipizide

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

• glyburide

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

• glycopyrrolate

  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.

• isavuconazonium sulfate

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

• 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.

• mavacamten

  orphenadrine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• melatonin

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

• meclizine

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

• meclofenamate

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

• mefenamic acid

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

• melatonin

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

• 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.

• sparsentan

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

• spironolactone

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

• stiripentol

  stiripentol, 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

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

• 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 (138)

• aceclofenac

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

• acemetacin

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

• acetazolamide

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

• acyclovir

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

• 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.

• anastrozole

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

• ceritinib

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

• chlorothiazide

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

• chlorpromazine

  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.

• cyclophosphamide

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

• larotrectinib

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

• levoketoconazole

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

• mexiletine

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

• 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.

• ruxolitinib topical

  orphenadrine will increase the level or effect of ruxolitinib topical 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.

• abametapir

  Serious - Use Alternative (1)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.

• abciximab

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

• abobotulinumtoxinA

  Monitor Closely (2)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.

• abrocitinib

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

• acalabrutinib

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

• acebutolol

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

• aceclofenac

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

• acemetacin

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

• acetazolamide

  Monitor Closely (2)acetazolamide, aspirin. 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).Minor (1)aspirin will decrease the level or effect of acetazolamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aclidinium

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

• acrivastine

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

• acyclovir

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

• adenosine

  Minor (1)caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.

• agrimony

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

• albuterol

  Monitor Closely (2)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.

• alendronate

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

• alfalfa

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

• alfentanil

  Monitor Closely (2)alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine and alfentanil both increase sedation. Use Caution/Monitor.

• alfuzosin

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

• aliskiren

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

• alprazolam

  Monitor Closely (2)alprazolam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alteplase

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

• aluminum hydroxide

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

• amantadine

  Minor (1)amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

• American ginseng

  Minor (1)American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• amikacin

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

• amiloride

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

• aminohippurate sodium

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

• amisulpride

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

• amitriptyline

  Monitor Closely (3)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (2)amobarbital and orphenadrine both increase sedation. Use Caution/Monitor.
  
  amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (3)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

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

• ampicillin

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

• anagrelide

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

• anamu

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

• anastrozole

  Minor (1)aspirin will decrease the level or effect of anastrozole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anticholinergic/sedative combos

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

• antithrombin alfa

  Monitor Closely (2)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 alfa and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• antithrombin III

  Monitor Closely (2)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.
  
  antithrombin III and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• apixaban

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

• apomorphine

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

• arformoterol

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

• argatroban

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

• aripiprazole

  Monitor Closely (2)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

  Monitor Closely (1)armodafinil and caffeine both decrease sedation. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ascorbic acid

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

• asenapine

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

• asenapine transdermal

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

• atenolol

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• avapritinib

  Monitor Closely (2)orphenadrine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  avapritinib and orphenadrine both increase sedation. Use Caution/Monitor.

• axitinib

  Monitor Closely (1)orphenadrine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  Monitor Closely (2)azelastine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• azficel-T

  Monitor Closely (1)azficel-T, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking aspirin may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of aspirin is not recommended. .

• azilsartan

  Monitor Closely (2)aspirin, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

• baclofen

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

• balsalazide

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

• belladonna alkaloids

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

• belladonna and opium

  Monitor Closely (3)orphenadrine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  belladonna and opium and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• bemiparin

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

• benazepril

  Monitor Closely (1)benazepril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• bendroflumethiazide

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

• benperidol

  Monitor Closely (2)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.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (2)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.
  
  benzhydrocodone/acetaminophen and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  Monitor Closely (2)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

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

• betaxolol

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

• bethanechol

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

• betrixaban

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

• bimatoprost

  Monitor Closely (1)bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• bismuth subsalicylate

  Minor (1)bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

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

• bivalirudin

  Monitor Closely (2)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.
  
  bivalirudin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• brexanolone

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

• brexpiprazole

  Monitor Closely (1)brexpiprazole and orphenadrine both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and orphenadrine both increase sedation. Use Caution/Monitor.

• brinzolamide

  Monitor Closely (1)brinzolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• brivaracetam

  Monitor Closely (1)brivaracetam and orphenadrine both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (2)brompheniramine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bumetanide

  Monitor Closely (2)aspirin decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  aspirin increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)aspirin, bumetanide. Other (see comment). Minor/Significance Unknown. Comment: Salicylates are less likely than other NSAIDs to interact w/bumetanide.

• buprenorphine

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

• buprenorphine buccal

  Monitor Closely (2)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 subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)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.

• bupropion

  Serious - Use Alternative (1)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.

• butabarbital

  Monitor Closely (2)butabarbital and orphenadrine both increase sedation. Use Caution/Monitor.
  
  butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butalbital

  Monitor Closely (2)butalbital and orphenadrine both increase sedation. Use Caution/Monitor.
  
  butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• butorphanol

  Monitor Closely (2)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.

• calcium acetate

  Minor (1)caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.

• calcium carbonate

  Minor (2)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

  Minor (1)caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.

• calcium citrate

  Minor (1)caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.

• calcium gluconate

  Minor (1)caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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.

• candesartan

  Monitor Closely (3)candesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  candesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• caplacizumab

  Serious - Use Alternative (1)caplacizumab, aspirin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug.

• captopril

  Monitor Closely (1)captopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• carbachol

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

• carbamazepine

  Minor (1)carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• carbenoxolone

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

• carbinoxamine

  Monitor Closely (2)carbinoxamine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carisoprodol

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

• carvedilol

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

• cefadroxil

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

• cefamandole

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

• cefepime

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

• cefixime

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

• cefpirome

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

• cefprozil

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

• ceftazidime

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

• ceftibuten

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

• celecoxib

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

• celiprolol

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

• cephalexin

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

• ceritinib

  Minor (1)aspirin will decrease the level or effect of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cevimeline

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

• chloral hydrate

  Monitor Closely (2)chloral hydrate and orphenadrine both increase sedation. Use Caution/Monitor.
  
  chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (2)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

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

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (2)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.Minor (1)orphenadrine decreases levels of chlorpromazine by unknown mechanism. Minor/Significance Unknown. Excessive anticholinergic effects and/or hypoglycemia possible.

• chlorpropamide

  Monitor Closely (1)aspirin increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (2)aspirin will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  aspirin increases effects of chlorpropamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• chlorthalidone

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

• chlorzoxazone

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

• choline magnesium trisalicylate

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

• chromium

  Minor (1)aspirin increases levels of chromium by unspecified interaction mechanism. Minor/Significance Unknown.

• cigarette smoking

  Minor (1)cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cilostazol

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

• cimetidine

  Minor (1)cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• cinnamon

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

• cinnarizine

  Monitor Closely (2)cinnarizine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ciprofloxacin

  Monitor Closely (2)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

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

• citalopram

  Monitor Closely (1)citalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

• clemastine

  Monitor Closely (2)clemastine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clomipramine

  Monitor Closely (4)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

  Monitor Closely (2)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.

• clonidine

  Serious - Use Alternative (1)clonidine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• clopidogrel

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

• clorazepate

  Monitor Closely (2)clorazepate and orphenadrine both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clotrimazole

  Minor (1)clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• clozapine

  Monitor Closely (2)orphenadrine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• codeine

  Monitor Closely (2)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

  Monitor Closely (1)aspirin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

• cordyceps

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

• cortisone

  Monitor Closely (1)aspirin, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)cortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• creatine

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

• cyanocobalamin

  Minor (1)aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (3)cyclizine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  cyclizine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cyclobenzaprine

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

• cyclopenthiazide

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

• cyclophosphamide

  Minor (1)aspirin will decrease the level or effect of cyclophosphamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyproheptadine

  Monitor Closely (2)cyproheptadine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dabigatran

  Monitor Closely (1)dabigatran and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin

• dalteparin

  Monitor Closely (2)aspirin, dalteparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.
  
  dalteparin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.

• danshen

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

• dantrolene

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

• daridorexant

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

• darifenacin

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

• deferasirox

  Monitor Closely (2)deferasirox, aspirin. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.
  
  deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• defibrotide

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

• deflazacort

  Monitor Closely (1)aspirin, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)deflazacort decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• desipramine

  Monitor Closely (3)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

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

• devil's claw

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

• dexamethasone

  Monitor Closely (1)aspirin, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)dexamethasone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)orphenadrine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (2)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

  Monitor Closely (1)caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (1)caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor.

• dextromoramide

  Monitor Closely (2)orphenadrine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  Monitor Closely (2)orphenadrine and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diazepam

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

• dichlorphenamide

  Contraindicated (1)dichlorphenamide increases levels of aspirin by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

• diclofenac

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

• diclofenac topical

  Minor (1)diclofenac topical, aspirin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

• dicloxacillin

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

• dicyclomine

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

• diethylpropion

  Monitor Closely (1)caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.

• difelikefalin

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

• difenoxin hcl

  Monitor Closely (2)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

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

• digoxin

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

• diltiazem

  Minor (1)diltiazem increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

• dimenhydrinate

  Monitor Closely (2)dimenhydrinate and orphenadrine both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (3)diphenhydramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)aspirin, dipyridamole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.Serious - Use Alternative (1)caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.

• dobutamine

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

• donepezil

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

• dong quai

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

• dopamine

  Monitor Closely (1)caffeine and dopamine both decrease sedation. Use Caution/Monitor.

• dopexamine

  Monitor Closely (3)aspirin increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and caffeine both decrease sedation. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)orphenadrine and dosulepin both increase sedation. Use Caution/Monitor.

• doxazosin

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

• doxepin

  Monitor Closely (3)orphenadrine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  doxepin and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• doxylamine

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

• droperidol

  Monitor Closely (2)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

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

• droxidopa

  Monitor Closely (1)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

  Monitor Closely (1)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

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

• edoxaban

  Monitor Closely (1)edoxaban, aspirin. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF, aspirin. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• enalapril

  Monitor Closely (1)enalapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• enoxaparin

  Monitor Closely (2)enoxaparin and aspirin both increase anticoagulation. Use Caution/Monitor. Additive effects are intended when both drugs are prescribed as indicated for unstable angina, non-Q-wave MI, and STEMI
  
  aspirin, enoxaparin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and anticoagulant or antiplatelet agents are common for patients with cardiovascular disease; monitor closely.

• ephedrine

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (2)aspirin increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.

• eplerenone

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

• epoprostenol

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

• eprosartan

  Monitor Closely (3)aspirin decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  eprosartan and aspirin both increase serum potassium. Use Caution/Monitor.
  
  eprosartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

• eptifibatide

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

• erythromycin base

  Minor (1)erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  Minor (1)erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin lactobionate

  Minor (1)erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• erythromycin stearate

  Minor (1)erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• escitalopram

  Monitor Closely (1)escitalopram, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• esketamine intranasal

  Monitor Closely (2)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

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

• estazolam

  Monitor Closely (2)estazolam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethacrynic acid

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

• ethanol

  Monitor Closely (2)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.Minor (1)ethanol increases toxicity of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI bleeding.

• ethinylestradiol

  Monitor Closely (1)ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• etodolac

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

• etomidate

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

• eucalyptus

  Minor (2)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.

• fedratinib

  Serious - Use Alternative (1)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.

• fenbufen

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

• fenfluramine

  Monitor Closely (2)orphenadrine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.

• fennel

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

• fenoprofen

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

• fesoterodine

  Monitor Closely (1)fesoterodine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• feverfew

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

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• fezolinetant

  Contraindicated (2)orphenadrine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
  
  caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• finerenone

  Monitor Closely (1)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

  Monitor Closely (1)fish oil, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• fish oil triglycerides

  Monitor Closely (1)fish oil triglycerides will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

• flavoxate

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

• flibanserin

  Monitor Closely (1)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.

• fluconazole

  Minor (1)fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (1)aspirin, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)fludrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)fluoxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• fluphenazine

  Monitor Closely (2)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

  Monitor Closely (2)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

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

• fluvoxamine

  Monitor Closely (2)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.
  
  fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• folic acid

  Minor (1)aspirin decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fondaparinux

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

• formoterol

  Monitor Closely (2)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

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

• fosinopril

  Monitor Closely (1)fosinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• furosemide

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

• galantamine

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

• ganaxolone

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

• ganciclovir

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

• garlic

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

• gentamicin

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

• ginger

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

• ginkgo biloba

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

• givosiran

  Serious - Use Alternative (1)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.

• glimepiride

  Monitor Closely (1)aspirin increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glimepiride by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glipizide

  Monitor Closely (1)aspirin increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glipizide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glucagon

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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. .

• glyburide

  Monitor Closely (1)aspirin increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of glyburide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• glycopyrrolate

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

• glycopyrrolate inhaled

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

• grapefruit

  Minor (1)grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• green tea

  Monitor Closely (2)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.
  
  green tea increases effects of aspirin by pharmacodynamic synergism. Use Caution/Monitor. (Theoretical, due to caffeine content). Combination may increase risk of bleeding.

• griseofulvin

  Monitor Closely (1)griseofulvin decreases levels of aspirin by unknown mechanism. Use Caution/Monitor.

• guarana

  Minor (1)guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• guselkumab

  Monitor Closely (1)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

  Monitor Closely (2)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

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

• homatropine

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

• horse chestnut seed

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

• huperzine A

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

• hyaluronidase

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

• hydralazine

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

• hydrochlorothiazide

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

• hydrocodone

  Serious - Use Alternative (1)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.

• hydrocortisone

  Monitor Closely (1)aspirin, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)hydrocortisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• hydromorphone

  Monitor Closely (2)orphenadrine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (2)hydroxyzine and orphenadrine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hyoscyamine

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

• hyoscyamine spray

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

• ibrutinib

  Monitor Closely (1)ibrutinib will increase the level or effect of aspirin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

• ibuprofen

  Monitor Closely (2)aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.
  
  aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (2)ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.
  
  ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.Minor (1)aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (3)aspirin will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
  
  aspirin and ibuprofen IV both increase serum potassium. Use Caution/Monitor.Serious - Use Alternative (2)ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.
  
  ibuprofen IV decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

• icosapent

  Monitor Closely (1)icosapent, aspirin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time; monitor periodically if coadministered with other drugs that affect bleeding.

• iloperidone

  Monitor Closely (2)orphenadrine and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• imatinib

  Monitor Closely (1)imatinib, aspirin. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

• imidapril

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

• imipramine

  Monitor Closely (3)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

  Monitor Closely (1)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.

• indapamide

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

• indomethacin

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

• insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin aspart protamine/insulin aspart

  Monitor Closely (1)aspirin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec

  Monitor Closely (1)aspirin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin degludec/insulin aspart

  Monitor Closely (1)aspirin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

• insulin detemir

  Monitor Closely (1)aspirin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glargine

  Monitor Closely (1)aspirin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin glulisine

  Monitor Closely (1)aspirin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin inhaled

  Monitor Closely (1)aspirin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin isophane human/insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin lispro protamine/insulin lispro

  Monitor Closely (1)aspirin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin NPH

  Monitor Closely (1)aspirin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• insulin regular human

  Monitor Closely (1)aspirin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of insulin with high doses of salicylates (3 g/day or more) may increase risk for hypoglycemia. Insulin dose adjustment and increased frequency of glucose monitoring may be required.

• iobenguane I 131

  Serious - Use Alternative (1)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.

• ipratropium

  Monitor Closely (1)ipratropium and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• irbesartan

  Monitor Closely (3)irbesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of irbesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  irbesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• isavuconazonium sulfate

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

• isocarboxazid

  Contraindicated (1)isocarboxazid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• isoniazid

  Minor (1)isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• isoproterenol

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

• itraconazole

  Minor (1)itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ivacaftor

  Monitor Closely (1)orphenadrine increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• ketamine

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

• ketoconazole

  Minor (1)ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• ketoprofen

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

• ketorolac

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

• ketorolac intranasal

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

• ketotifen, ophthalmic

  Monitor Closely (2)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.

• L-methylfolate

  Minor (1)aspirin decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• labetalol

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

• larotrectinib

  Minor (1)aspirin will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• latanoprost

  Monitor Closely (1)latanoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• latanoprostene bunod ophthalmic

  Monitor Closely (1)latanoprostene bunod ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• lemborexant

  Monitor Closely (1)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.

• lesinurad

  Serious - Use Alternative (1)aspirin decreases effects of lesinurad by unspecified interaction mechanism. Avoid or Use Alternate Drug. Aspirin at doses >325 mg/day may decrease lesinurad efficacy. Aspirin doses 325 mg/day or less (ie, for cardiovascular event prophylaxis) does not decrease lesinurad efficacy and can be coadministered.

• letermovir

  Monitor Closely (1)letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (2)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.

• levoketoconazole

  Minor (2)levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
  
  aspirin will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

• levorphanol

  Monitor Closely (2)levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)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.

• linezolid

  Contraindicated (1)linezolid increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• lisdexamfetamine

  Monitor Closely (1)caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.

• lisinopril

  Monitor Closely (1)lisinopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• lithium

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

• lofepramine

  Monitor Closely (3)lofepramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofexidine

  Monitor Closely (2)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

  Monitor Closely (1)orphenadrine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)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.

• loprazolam

  Monitor Closely (2)loprazolam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lorazepam

  Monitor Closely (2)lorazepam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lormetazepam

  Monitor Closely (2)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

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

• losartan

  Monitor Closely (3)losartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  losartan and aspirin both increase serum potassium. Use Caution/Monitor.

• loxapine

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

• loxapine inhaled

  Monitor Closely (2)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

  Monitor Closely (1)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.

• macimorelin

  Serious - Use Alternative (1)aspirin, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that directly affect the pituitary secretion of growth hormone (GH) may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin. .

• maprotiline

  Monitor Closely (3)maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  maprotiline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and maprotiline both increase sedation. Use Caution/Monitor.

• marijuana

  Monitor Closely (2)orphenadrine and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mavacamten

  Monitor Closely (1)orphenadrine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• measles, mumps, rubella and varicella vaccine, live

  Serious - Use Alternative (1)aspirin, measles, mumps, rubella and varicella vaccine, live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• meclizine

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

• meclofenamate

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

• mefenamic acid

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

• melatonin

  Monitor Closely (3)melatonin increases effects of aspirin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.
  
  melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

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

• meperidine

  Monitor Closely (2)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

  Monitor Closely (2)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

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

• metaproterenol

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

• metaxalone

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

• methadone

  Monitor Closely (2)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

  Monitor Closely (1)caffeine and methamphetamine both decrease sedation. Use Caution/Monitor.

• methazolamide

  Monitor Closely (1)methazolamide, aspirin. Either increases levels of the other by Other (see comment). Use Caution/Monitor. Comment: Carbonic anhydrase inhibitors (CAIs) and salicylates inhibit each other's renal tubular secretion, resulting in increased plasma levels. CAIs also shift salicylates from plasma to the CNS, leading to potential neurotoxicity.

• methocarbamol

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

• methotrexate

  Monitor Closely (1)caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.Serious - Use Alternative (1)aspirin increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Caution should be exercised when salicylates are given in combination with methotrexate. Risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses.

• methscopolamine

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

• methyclothiazide

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

• methylenedioxymethamphetamine

  Monitor Closely (2)orphenadrine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.

• methylphenidate

  Monitor Closely (1)caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• methylprednisolone

  Monitor Closely (1)aspirin, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)methylprednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• metolazone

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

• metoprolol

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

• mexiletine

  Minor (1)mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (2)midazolam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)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

  Monitor Closely (1)caffeine and midodrine both decrease sedation. Use Caution/Monitor.

• mifepristone

  Contraindicated (1)aspirin, mifepristone. Other (see comment). Contraindicated. Comment: Aspirin induced antiplatelet activity may induce excessive bleeding after an abortion w/mifepristone (RU 486).Serious - Use Alternative (1)aspirin will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• milnacipran

  Monitor Closely (1)milnacipran, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• mirtazapine

  Monitor Closely (2)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

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

• mitotane

  Serious - Use Alternative (1)aspirin will decrease the level or effect of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Monitor Closely (1)caffeine and modafinil both decrease sedation. Use Caution/Monitor.Minor (1)modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• moexipril

  Monitor Closely (1)moexipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• morphine

  Monitor Closely (2)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

  Monitor Closely (2)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

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

• moxonidine

  Monitor Closely (2)orphenadrine and moxonidine both increase sedation. Use Caution/Monitor.
  
  moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mycophenolate

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

• nabilone

  Monitor Closely (2)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

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

• nadolol

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

• nafcillin

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

• nalbuphine

  Monitor Closely (2)orphenadrine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• naproxen

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

• nebivolol

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

• nefazodone

  Monitor Closely (1)nefazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• neomycin PO

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

• neostigmine

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

• nettle

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

• nitazoxanide

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

• nitroglycerin rectal

  Monitor Closely (1)aspirin will increase the level or effect of nitroglycerin rectal by Other (see comment). Use Caution/Monitor. The pharmacological effects of nitroglycerin may be enhanced by concomitant administration of aspirin.

• nitroglycerin sublingual

  Monitor Closely (1)aspirin increases effects of nitroglycerin sublingual by additive vasodilation. Use Caution/Monitor. Vasodilatory and hemodynamic effects of NTG may be enhanced by coadministration with aspirin (additive effect desirable for emergent treatment).

• noni juice

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

• norepinephrine

  Monitor Closely (2)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

  Monitor Closely (3)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.

• ofloxacin

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

• olanzapine

  Monitor Closely (2)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

  Monitor Closely (2)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.

• olmesartan

  Monitor Closely (3)olmesartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  olmesartan and aspirin both increase serum potassium. Use Caution/Monitor.

• olopatadine intranasal

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

• omega 3 carboxylic acids

  Monitor Closely (1)omega 3 carboxylic acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

• omega 3 fatty acids

  Monitor Closely (1)omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. .

• onabotulinumtoxinA

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

• opium tincture

  Monitor Closely (2)orphenadrine and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ospemifene

  Monitor Closely (1)aspirin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxacillin

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

• oxaprozin

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

• oxazepam

  Monitor Closely (2)oxazepam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

  Monitor Closely (2)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (2)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.

• ozanimod

  Serious - Use Alternative (1)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.

• paliperidone

  Monitor Closely (2)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

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

• pancuronium

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

• papaveretum

  Monitor Closely (2)orphenadrine and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaverine

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

• parecoxib

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

• paromomycin

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

• paroxetine

  Monitor Closely (1)paroxetine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• pau d'arco

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

• pefloxacin

  Monitor Closely (1)pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• pegaspargase

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

• peginterferon alfa 2a

  Minor (1)peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• pemetrexed

  Serious - Use Alternative (1)aspirin increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Interrupt dosing in all patients taking NSAIDs with long elimination half-lives for at least 5d before, the day of, and 2d following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor patients for toxicity, especially myelosuppression, renal toxicity, and GI toxicity.

• penbutolol

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

• penicillin G aqueous

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

• penicillin VK

  Minor (1)penicillin VK, aspirin. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown.

• pentazocine

  Monitor Closely (2)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.Minor (1)aspirin, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible risk of renal papillary necrosis w/chronic Tx.

• pentobarbital

  Monitor Closely (2)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.Minor (1)pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)perindopril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin,in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• perphenazine

  Monitor Closely (2)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  Monitor Closely (1)caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.

• phenelzine

  Contraindicated (1)phenelzine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• phenindione

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

• phenobarbital

  Monitor Closely (2)phenobarbital and orphenadrine both increase sedation. Use Caution/Monitor.
  
  phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• phenoxybenzamine

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

• phentermine

  Monitor Closely (1)caffeine and phentermine both decrease sedation. Use Caution/Monitor.

• phentolamine

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

• phenylephrine

  Monitor Closely (1)caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (2)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

  Monitor Closely (2)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

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

• phytoestrogens

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

• pilocarpine

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

• pimozide

  Monitor Closely (2)orphenadrine and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pindolol

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

• pipemidic acid

  Minor (1)pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• piperacillin

  Minor (1)piperacillin, aspirin. Either increases effects of the other by receptor binding competition. Minor/Significance Unknown. Salicylic acid could be displaced from protein binding sites or it could itself displace other protein-bound drugs and result in an enhanced effect of the displaced drug.

• pirbuterol

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

• piroxicam

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

• pivmecillinam

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

• posaconazole

  Minor (1)posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• potassium acid phosphate

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

• potassium chloride

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

• potassium citrate

  Monitor Closely (1)aspirin and potassium citrate both increase serum potassium. Use Caution/Monitor.

• potassium iodide

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

• prabotulinumtoxinA

  Monitor Closely (1)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

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

• prasugrel

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

• prazosin

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

• prednisolone

  Monitor Closely (1)aspirin, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)prednisolone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• prednisone

  Monitor Closely (1)aspirin, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.Minor (1)prednisone decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• primidone

  Monitor Closely (2)primidone and orphenadrine both increase sedation. Use Caution/Monitor.
  
  primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• probenecid

  Serious - Use Alternative (1)aspirin decreases effects of probenecid by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Aspirin decreases uricosuric action of probenecid.

• procarbazine

  Contraindicated (1)procarbazine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Caffeine can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking a MAOI. All preparations containing caffeine should be used sparingly.

• prochlorperazine

  Monitor Closely (2)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

  Monitor Closely (2)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

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

• propofol

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

• propranolol

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

• propylhexedrine

  Monitor Closely (2)orphenadrine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.

• protamine

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

• protriptyline

  Monitor Closely (3)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

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

• quazepam

  Monitor Closely (2)quazepam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)orphenadrine and quetiapine both increase sedation. Use Caution/Monitor.
  
  quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quinapril

  Monitor Closely (1)quinapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, quinapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• ramelteon

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

• ramipril

  Monitor Closely (1)ramipril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high doses of aspirin, in elderly or volume depleted individuals.Serious - Use Alternative (1)aspirin, ramipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• rapacuronium

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

• rasagiline

  Monitor Closely (1)rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

• regadenoson

  Serious - Use Alternative (1)caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

• reishi

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

• remimazolam

  Monitor Closely (1)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

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

• rifampin

  Minor (1)rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• risperidone

  Monitor Closely (2)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

  Monitor Closely (1)aspirin, rivaroxaban. Either increases toxicity of the other by anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. The need for simultaneous use of low-dose aspirin (<100 mg/day) with anticoagulants are common for patients with cardiovascular disease, but may result in increased bleeding; monitor closely. Promptly evaluate any signs or symptoms of blood loss if treated concomitantly with low-dose aspirin. Avoid coadministration with chronic use of higher dose aspirin.

• rivastigmine

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

• rocuronium

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

• rose hips

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

• rucaparib

  Monitor Closely (1)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.

• ruxolitinib

  Minor (1)orphenadrine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)orphenadrine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sacubitril/valsartan

  Monitor Closely (3)sacubitril/valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  sacubitril/valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

• sage

  Minor (2)orphenadrine and sage both increase sedation. Minor/Significance Unknown.
  
  sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• salicylates (non-asa)

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

• salmeterol

  Monitor Closely (2)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

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

• saw palmetto

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

• scopolamine

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

• scullcap

  Monitor Closely (2)orphenadrine and scullcap both increase sedation. Use Caution/Monitor.
  
  scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• secobarbital

  Monitor Closely (2)secobarbital and orphenadrine both increase sedation. Use Caution/Monitor.
  
  secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• selegiline

  Monitor Closely (1)selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• selumetinib

  Monitor Closely (1)aspirin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

• sertraline

  Monitor Closely (1)sertraline, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• shepherd's purse

  Monitor Closely (2)orphenadrine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• Siberian ginseng

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

• silodosin

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

• smoking

  Minor (1)smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• sodium bicarbonate

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

• sodium citrate/citric acid

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

• sodium oxybate

  Serious - Use Alternative (1)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.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  Monitor Closely (1)aspirin, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of aspirin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• solifenacin

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

• solriamfetol

  Monitor Closely (1)caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sotalol

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

• sparsentan

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

• spironolactone

  Monitor Closely (2)aspirin decreases effects of spironolactone by unspecified interaction mechanism. Use Caution/Monitor. When used concomitantly, spironolactone dose may need to be titrated to higher maintenance dose and the patient should be observed closely to determine if the desired effect is obtained.
  
  spironolactone and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.

• stiripentol

  Monitor Closely (2)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.Minor (1)aspirin will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• streptomycin

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

• succinylcholine

  Monitor Closely (2)aspirin and succinylcholine both increase serum potassium. Use Caution/Monitor.
  
  succinylcholine increases and orphenadrine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

  Monitor Closely (2)orphenadrine and sufentanil both increase sedation. Use Caution/Monitor.
  
  sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.

• sulfadiazine

  Minor (1)aspirin increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Monitor Closely (1)aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• sulfasalazine

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

• sulfisoxazole

  Minor (1)aspirin increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

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

• tafluprost

  Monitor Closely (1)tafluprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• tapentadol

  Monitor Closely (2)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

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

• telmisartan

  Monitor Closely (3)telmisartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  telmisartan and aspirin both increase serum potassium. Use Caution/Monitor.

• temazepam

  Monitor Closely (2)temazepam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• temocillin

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

• tenecteplase

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

• teniposide

  Minor (1)aspirin increases levels of teniposide by unspecified interaction mechanism. Minor/Significance Unknown.

• terazosin

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

• terbutaline

  Monitor Closely (2)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

  Monitor Closely (1)teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• thiamine

  Minor (1)caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.

• thioridazine

  Monitor Closely (2)orphenadrine and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thiothixene

  Monitor Closely (2)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

  Monitor Closely (1)aspirin, ticagrelor. Other (see comment). Use Caution/Monitor. Comment: Maintenance doses of aspirin above 100 mg decreases effectiveness of ticagrelor. Therefore, after the initial loading dose of aspirin (usually 325 mg), use ticagrelor with a maintenance dose of aspirin of 75-100 mg.

• ticarcillin

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

• ticlopidine

  Serious - Use Alternative (1)aspirin increases effects of ticlopidine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced risk of hemorrhage.

• tiludronate

  Minor (1)aspirin decreases levels of tiludronate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• timolol

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

• tinidazole

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

• tiotropium

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

• tirofiban

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

• tobacco use

  Minor (1)tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• tobramycin

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

• tobramycin inhaled

  Monitor Closely (1)tobramycin inhaled and aspirin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

• tolazamide

  Monitor Closely (1)aspirin increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of tolazamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolbutamide

  Monitor Closely (1)aspirin increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.Minor (1)aspirin increases effects of tolbutamide by plasma protein binding competition. Minor/Significance Unknown. Large dose of salicylate.

• tolfenamic acid

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

• tolmetin

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

• tolterodine

  Monitor Closely (1)tolterodine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolvaptan

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

• topiramate

  Monitor Closely (2)topiramate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  orphenadrine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• torsemide

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

• tramadol

  Monitor Closely (2)orphenadrine and tramadol both increase sedation. Use Caution/Monitor.
  
  tramadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trandolapril

  Monitor Closely (1)trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.Serious - Use Alternative (1)aspirin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of caffeine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• travoprost ophthalmic

  Monitor Closely (1)travoprost ophthalmic, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

• trazodone

  Monitor Closely (4)trazodone and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  trazodone, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.
  
  orphenadrine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)aspirin, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Aspirin in conjunction with corticosteroids in hypoprothrombinemia should used with caution. Clearance of salicylates may increase with concurrent use of corticosteroids.Minor (1)triamcinolone acetonide injectable suspension decreases levels of aspirin by increasing renal clearance. Minor/Significance Unknown.

• triamterene

  Monitor Closely (1)triamterene and aspirin both increase serum potassium. Modify Therapy/Monitor Closely.Minor (2)triamterene, aspirin. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.
  
  aspirin increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

• triazolam

  Monitor Closely (2)triazolam and orphenadrine both increase sedation. Use Caution/Monitor.
  
  triazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)triclofos and orphenadrine both increase sedation. Use Caution/Monitor.
  
  triclofos increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)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

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

• trimipramine

  Monitor Closely (3)orphenadrine and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  trimipramine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• triprolidine

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

• trospium chloride

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

• valganciclovir

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

• valproic acid

  Monitor Closely (1)aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

• valsartan

  Monitor Closely (3)valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.
  
  aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.
  
  valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

• vancomycin

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

• varicella virus vaccine live

  Serious - Use Alternative (1)aspirin, varicella virus vaccine live. Mechanism: unspecified interaction mechanism. Avoid or Use Alternate Drug. Risk of Reye's Syndrome with combination; avoid salicylate use for 6 wks after vaccination.

• vecuronium

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

• venlafaxine

  Monitor Closely (1)venlafaxine, aspirin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

• verapamil

  Minor (2)verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.
  
  verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• voclosporin

  Monitor Closely (1)voclosporin, aspirin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vorapaxar

  Monitor Closely (2)aspirin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.
  
  aspirin, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

• voriconazole

  Minor (1)voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.

• vortioxetine

  Monitor Closely (1)aspirin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Risk minimal with low-dose aspirin.

• warfarin

  Monitor Closely (1)aspirin increases effects of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Avoid coadministration of chronic high-dose aspirin. Aspirin's antiplatelet properties may increase anticoagulation effect of warfarin. The need for simultaneous use of low-dose aspirin and warfarin is common for patients with cardiovascular disease. .

• willow bark

  Minor (2)aspirin will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  willow bark increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

• xylometazoline

  Monitor Closely (2)orphenadrine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and xylometazoline both decrease sedation. Use Caution/Monitor.

• yerba mate

  Minor (1)yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.

• yohimbine

  Monitor Closely (1)caffeine and yohimbine both decrease sedation. Use Caution/Monitor.

• zafirlukast

  Minor (1)aspirin increases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

• zanubrutinib

  Monitor Closely (1)aspirin, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

• ziconotide

  Monitor Closely (2)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.

• zileuton

  Minor (1)zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ziprasidone

  Monitor Closely (2)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.

• zoledronic acid

  Minor (1)aspirin decreases levels of zoledronic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• zotepine

  Monitor Closely (2)aspirin decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.
  
  orphenadrine and zotepine both increase sedation. Use Caution/Monitor.