acetaminophen/ibuprofen (Rx, OTC)

Brand and Other Names:Advil Dual Action, Combogesic

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

acetaminophen/ibuprofen

tablet

  • 250mg/125mg (Advil Dual Action; OTC)
  • 325mg/97.5mg (Combogesic; Rx)

Pain

Advil Dual Action

  • Indicated for temporary relief of mild pain caused by headache, backache, muscular aches, toothache, menstrual cramps, minor pain of arthritis
  • 2 tablets PO (500 mg acetaminophen / 250 mg ibuprofen) q8hr while symptoms persist; not to exceed 6 tablets/day, unless directed by physician

Combogesic

  • Indicated in adults for short-term management of mild-to-moderate acute pain
  • 3 tablets (975 mg acetaminophen / 292.5 mg ibuprofen) PO q6hr PRN; not to exceed 12 tablets/day

Dosage Modifications

Renal or hepatic impairment

  • Not studied; not recommended

Dosing Considerations

Consider monitoring patients on long-term treatment with CBC and a chemistry profile periodically to monitor for serious GI bleeding, hepatotoxicity, and renal injury

Dosage Forms & Strengths

acetaminophen/ibuprofen

tablet

  • 250mg/125mg (Advil Dual Action; OTC)

Pain

Indicated for temporary relief of mild pain caused by headache, backache, muscular aches, toothache, menstrual cramps, minor pain of arthritis

Advil Dual Action

  • <12 years: Safety and efficacy not established
  • ≥12 years: 2 tablets (500 mg acetaminophen / 250 mg ibuprofen) PO q8hr while symptoms persist; not to exceed 6 tablets/day, unless directed by physician

Dosage Modifications

Renal or hepatic impairment

  • Not studied; not recommended

Dosing Considerations

Consider monitoring patients on long-term treatment with CBC and a chemistry profile periodically to monitor for serious GI bleeding, hepatotoxicity, and renal injury

Next:

Interactions

Interaction Checker

and acetaminophen/ibuprofen

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              Serious - Use Alternative (29)

              • aminolevulinic acid oral

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

              • aminolevulinic acid topical

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

              • apixaban

                ibuprofen and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

              • aspirin

                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.

              • aspirin rectal

                ibuprofen decreases effects of aspirin rectal by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of aspirin by blocking the active site of platelet cyclooxygenase. The effect of other NSAIDs on aspirin is not established.

              • aspirin/citric acid/sodium bicarbonate

                ibuprofen decreases effects of aspirin/citric acid/sodium bicarbonate by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of aspirin by blocking the active site of platelet cyclooxygenase. The effect of other NSAIDs on aspirin is not established.

              • benazepril

                ibuprofen, 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.

              • captopril

                ibuprofen, 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.

              • enalapril

                ibuprofen, 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.

              • erdafitinib

                ibuprofen will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

              • fosinopril

                ibuprofen, 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.

              • ketorolac

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

              • ketorolac intranasal

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

              • lisinopril

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

              • lonafarnib

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

              • methotrexate

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

              • methyl aminolevulinate

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

              • moexipril

                ibuprofen, 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.

              • naproxen

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

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

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

              • oxaprozin

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

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

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

              • pemetrexed

                ibuprofen increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Especially in pts. w/mild moderate renal insufficiency. D/C NSAIDs 2 5 d before and 2 d after pemetrexed administration.

              • perindopril

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

              • pexidartinib

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

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

              • pretomanid

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

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

              • quinapril

                ibuprofen, 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

                ibuprofen, 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.

              • siponimod

                ibuprofen will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

              • tacrolimus

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

              • trandolapril

                ibuprofen, 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.

              Monitor Closely (269)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

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

              • agrimony

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

              • albuterol

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

              • alfalfa

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

              • alfuzosin

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

              • aliskiren

                ibuprofen 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.

              • alteplase

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

              • American ginseng

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

              • amikacin

                ibuprofen increases levels of amikacin by decreasing renal clearance. Use Caution/Monitor. Interaction mainly occurs in preterm infants.

              • amiloride

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

              • antithrombin alfa

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

              • antithrombin III

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

              • apalutamide

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

              • arformoterol

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

              • argatroban

                argatroban and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

              • asenapine

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

              • aspirin

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

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

              • aspirin rectal

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

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

              • aspirin/citric acid/sodium bicarbonate

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

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

              • atenolol

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

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

              • atogepant

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

              • avapritinib

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

              • axitinib

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

              • azficel-T

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

              • azilsartan

                ibuprofen, 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.

                ibuprofen 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.

              • bemiparin

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

              • benazepril

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

              • bendroflumethiazide

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

              • betaxolol

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

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

              • betrixaban

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

              • bimatoprost

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

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

              • bivalirudin

                bivalirudin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

              • budesonide

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

              • bumetanide

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

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

              • bupivacaine implant

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

              • busulfan

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

              • candesartan

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

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

              • captopril

                captopril, ibuprofen. 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.

              • carbamazepine

                ibuprofen will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor plasma levels when used concomitantly

              • carbenoxolone

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

              • carvedilol

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

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

              • celecoxib

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

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

              • celiprolol

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

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

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

              • cinnamon

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

              • ciprofloxacin

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

              • citalopram

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

              • clomipramine

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

              • clopidogrel

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

              • cordyceps

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

              • cortisone

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

              • cyclopenthiazide

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

              • cyclosporine

                ibuprofen, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

              • dabigatran

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

              • dalteparin

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

              • dapsone topical

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

              • deferasirox

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

              • defibrotide

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

              • deflazacort

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

              • dexamethasone

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

              • dichlorphenamide

                dichlorphenamide, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

              • diclofenac

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

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

              • diflunisal

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

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

              • digoxin

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

              • dobutamine

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

              • dong quai

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

              • dopexamine

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

              • doxazosin

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

              • dronabinol

                ibuprofen will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

              • drospirenone

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

              • duloxetine

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

              • edoxaban

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

              • efavirenz

                efavirenz will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • eltrombopag

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

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

              • eluxadoline

                ibuprofen increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

              • exenatide injectable solution

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

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

              • emtricitabine

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

              • enalapril

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

              • enoxaparin

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

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • eprosartan

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

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

              • escitalopram

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

              • esmolol

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

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

              • ethacrynic acid

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

              • etodolac

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

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

              • exenatide injectable suspension

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

              • fennel

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

              • fenoprofen

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

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

              • feverfew

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

              • finerenone

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

              • fish oil triglycerides

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

              • flibanserin

                acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

              • fludrocortisone

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

              • fluoxetine

                fluoxetine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

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

              • flurbiprofen

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

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

              • fluvoxamine

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

              • fondaparinux

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

              • formoterol

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

              • forskolin

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

              • fosinopril

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

              • furosemide

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

              • garlic

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

              • gemifloxacin

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

              • gentamicin

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

              • ginger

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

              • ginkgo biloba

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

                ibuprofen increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

              • green tea

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

              • heparin

                heparin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

              • horse chestnut seed

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

              • hydralazine

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

              • hydrochlorothiazide

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

              • hydrocortisone

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

              • ibrutinib

                ibrutinib will increase the level or effect of ibuprofen 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.

              • imatinib

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

                imatinib, ibuprofen. 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.

                imatinib will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • indapamide

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

              • isavuconazonium sulfate

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

              • indomethacin

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

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

              • irbesartan

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

                ibuprofen decreases effects of irbesartan by pharmacodynamic antagonism. Use Caution/Monitor. Antihypertensive effect of angiotensin receptor blockers may be attenuated by NSAIDs; monitor renal function and blood pressure periodically.

                irbesartan, ibuprofen. 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.

              • isoniazid

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

              • isoproterenol

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

              • ivacaftor

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

              • ketoprofen

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

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

              • ketorolac

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

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

              • ketorolac intranasal

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

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

              • labetalol

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

                ibuprofen decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs diminish antihypertensive effects of beta-blockers.

              • lacosamide

                ibuprofen increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP2C9 inhibitors.

              • latanoprost

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

              • lemborexant

                acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

              • lesinurad

                ibuprofen will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

              • levalbuterol

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

              • levofloxacin

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

              • levomilnacipran

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

              • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

                levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.

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

              • lisinopril

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

              • lithium

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

              • lixisenatide (DSC)

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

              • lomitapide

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

              • lornoxicam

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

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

              • losartan

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

                ibuprofen 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, ibuprofen. 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.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

              • meclofenamate

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

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

              • mefenamic acid

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

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

              • melatonin

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

              • meloxicam

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

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

              • mesalamine

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

              • metaproterenol

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • metoprolol

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

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

              • midazolam intranasal

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

              • milnacipran

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

              • mipomersen

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

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

              • mistletoe

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

              • tazemetostat

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

              • moexipril

                moexipril, ibuprofen. 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.

              • moxifloxacin

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

              • moxisylyte

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

              • mycophenolate

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

              • nabumetone

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

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

              • nadolol

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

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

              • nebivolol

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

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

              • nefazodone

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

              • nettle

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

              • norepinephrine

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

              • olmesartan

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

                ibuprofen 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, ibuprofen. 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.

              • ospemifene

                ibuprofen increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

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

              • panax ginseng

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

              • parecoxib

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

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

              • paroxetine

                paroxetine, ibuprofen. 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

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

              • pegaspargase

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

              • peginterferon alfa 2b

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

              • penbutolol

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

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

              • perindopril

                perindopril, ibuprofen. 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.

              • phenindione

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

              • phenoxybenzamine

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

              • phentolamine

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

              • phytoestrogens

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

              • pindolol

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

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

              • pirbuterol

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

              • piroxicam

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

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

              • pivmecillinam

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

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • potassium iodide

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

              • pralatrexate

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

              • prasugrel

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

              • prazosin

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

              • prednisolone

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

              • prednisone

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

              • probenecid

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

              • propranolol

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

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

              • protamine

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

              • quinapril

                quinapril, ibuprofen. 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.

              • ramipril

                ramipril, ibuprofen. 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.

              • reishi

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

              • reteplase

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

              • rivaroxaban

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

              • rivastigmine

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

              • sacubitril/valsartan

                sacubitril/valsartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

                sacubitril/valsartan, ibuprofen. 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.

                ibuprofen 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)

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

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

              • salmeterol

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

              • salsalate

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

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

              • saw palmetto

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

              • sertraline

                sertraline, ibuprofen. 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

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

              • silodosin

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

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

                ibuprofen, 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 ibuprofen 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 chloride/magnesium sulfate/polyethylene glycol

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

              • sodium sulfate/potassium sulfate/magnesium sulfate

                sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of ibuprofen 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.

              • sotalol

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

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

              • sparsentan

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

              • succinylcholine

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

              • sulfasalazine

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

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

              • sulindac

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

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

              • tafluprost

                tafluprost, ibuprofen. 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).

              • telmisartan

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

                ibuprofen 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, ibuprofen. 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.

              • temocillin

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

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

              • tenecteplase

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

              • tenofovir DF

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

              • terazosin

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

              • terbinafine

                ibuprofen will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • terbutaline

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

              • tetracaine

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

              • ticagrelor

                ticagrelor, ibuprofen. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Increased risk of bleeding with use of ticagrelor and chronic NSAID use. .

              • ticarcillin

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

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

              • ticlopidine

                ticlopidine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

                ticlopidine increases toxicity of ibuprofen by anticoagulation. Use Caution/Monitor.

              • timolol

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

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

              • tinidazole

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

              • tobramycin inhaled

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

              • tolazamide

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

              • tolbutamide

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

              • tolfenamic acid

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

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

              • tolmetin

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

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

              • tolvaptan

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

              • torsemide

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

              • trandolapril

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

              • travoprost ophthalmic

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

              • triamcinolone acetonide injectable suspension

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

              • triamterene

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

              • valoctocogene roxaparvovec

                ibuprofen and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.

              • valsartan

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

                ibuprofen 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, ibuprofen. 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.

              • venlafaxine

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

              • vitamin K1 (phytonadione)

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

              • voclosporin

                voclosporin, ibuprofen. 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

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

              • vortioxetine

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

              • warfarin

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

                acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

              • zanubrutinib

                ibuprofen, 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.

              • zotepine

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

              Minor (141)

              • aceclofenac

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

              • acemetacin

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

              • acetazolamide

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

              • acyclovir

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

              • adefovir

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

              • albiglutide

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

              • alendronate

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

              • aminohippurate sodium

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

              • amiodarone

                amiodarone will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • amobarbital

                amobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • anamu

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

              • antithrombin alfa

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

              • antithrombin III

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

              • argatroban

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

              • aspirin

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

              • aspirin rectal

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

              • aspirin/citric acid/sodium bicarbonate

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

              • balsalazide

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

              • bemiparin

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

              • bendroflumethiazide

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

              • bivalirudin

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

              • bosentan

                bosentan will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • butabarbital

                butabarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • butalbital

                butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • carbamazepine

                carbamazepine will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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

              • cefadroxil

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

              • cholestyramine

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

              • cefamandole

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

              • cefdinir

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

              • cefpirome

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

              • ceftibuten

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

              • celecoxib

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

              • cephalexin

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

              • cimetidine

                cimetidine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • clonazepam

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

              • colestipol

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

              • creatine

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

              • cyclopenthiazide

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

              • dalteparin

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

              • danshen

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

              • devil's claw

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

              • diazepam

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

              • diclofenac

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

              • diclofenac topical

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

              • diflunisal

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

              • digoxin

                ibuprofen increases levels of digoxin by decreasing renal clearance. Minor/Significance Unknown.

              • disulfiram

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

                disulfiram will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • enoxaparin

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

              • eplerenone

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

              • ethanol

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

                ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

              • ethosuximide

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

              • etodolac

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

              • etravirine

                etravirine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • felbamate

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

                felbamate will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • fenoprofen

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

              • fondaparinux

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

              • feverfew

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

              • fluconazole

                fluconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • flurbiprofen

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

              • fosphenytoin

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

              • furosemide

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

              • ganciclovir

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

              • gentamicin

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

              • green tea

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

              • heparin

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

              • hydrochlorothiazide

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

              • imidapril

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

              • indapamide

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

              • indomethacin

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

              • isoniazid

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

              • ketoconazole

                ketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • lacosamide

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

              • lamotrigine

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

              • leflunomide

                leflunomide will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • levetiracetam

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

              • levoketoconazole

                levoketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • liraglutide

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

              • lorazepam

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

              • lornoxicam

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

              • meclofenamate

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

              • mefenamic acid

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

              • meloxicam

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

              • mesalamine

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

              • methsuximide

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

              • methyclothiazide

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

              • metoclopramide

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

              • metolazone

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

              • metronidazole

                metronidazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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

              • miconazole vaginal

                miconazole vaginal will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • oxcarbazepine

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

              • nabumetone

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

              • nateglinide

                nateglinide will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • neomycin PO

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

              • nilotinib

                nilotinib will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • noni juice

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

              • ofloxacin

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

              • oxybutynin

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

              • oxybutynin topical

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

              • oxybutynin transdermal

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

              • parecoxib

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

              • paromomycin

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

              • pentobarbital

                pentobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • phenindione

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

              • phenobarbital

                phenobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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

              • phenytoin

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

              • piroxicam

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

              • primidone

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

                primidone will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • protamine

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

              • rifampin

                rifampin will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • rifabutin

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

              • rifampin

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

              • rifapentine

                rifapentine will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • rose hips

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

              • rufinamide

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

              • ruxolitinib

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

              • ruxolitinib topical

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

              • salicylates (non-asa)

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

              • salsalate

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

              • secobarbital

                secobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • streptomycin

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

              • sulfamethoxazole

                sulfamethoxazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • sulfasalazine

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

              • sulindac

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

              • tiagabine

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

              • tobramycin

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

              • tolfenamic acid

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

              • tolmetin

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

              • topiramate

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

              • treosulfan

                treosulfan decreases effects of ibuprofen by Mechanism: unspecified interaction mechanism. Minor/Significance Unknown.

              • triamterene

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

                ibuprofen increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

              • valganciclovir

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

              • valproic acid

                valproic acid will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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

              • vancomycin

                ibuprofen increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

              • zonisamide

                zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

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              Adverse Effects

              >10%

              Nausea (15%)

              1-10%

              Vomiting (7%)

              Headache (5%)

              Dizziness (3%)

              Somnolence (2%)

              Post-procedural hemorrhage (2%)

              Facial swelling (2%)

              Constipation (1%)

              <1%

              Dyspepsia (0.4%)

              Pruritus (0.4%)

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              Warnings

              Black Box Warnings

              Hepatotoxicity

              • Acetaminophen associated acute liver failure, at times resulting in liver transplant and death
              • Most cases of liver injury associated with acetaminophen are at doses >4,000 mg/day, and often involve more than 1 acetaminophen-containing product

              Cardiovascular risk

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

              Gastrointestinal risk

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

              Contraindications

              Known hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to acetaminophen, ibuprofen, other NSAIDs, or to any product excipients

              History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDS

              In the setting of coronary artery bypass graft (CABG) surgery

              Cautions

              Hepatotoxicity risk

              • Not studied in patients with impaired hepatic function and is not recommended
              • Acetaminophen
                • Acetaminophen associated with acute liver failure, at times resulting in liver transplant and death
                • Risk is higher with long-term high dose, or use of >1 acetaminophen-containing product
                • Acetaminophen is available in many dosage forms and products; check label carefully to avoid overdose
                • Limit acetaminophen dose from all sources and routes to <4 g/day in adults
              • Ibuprofen
                • Elevated ALT/AST (≥3 x ULN]) reported in ~1% of NSAID-treated patients in clinical trials, and up to 15% post-marketing
                • Additionally, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported

              Cardiovascular thrombotic events

              • Avoid use in patients with recent MI unless benefits are expected to outweigh risk of recurrent CV thrombotic events; if prescribed in such patients, monitor for signs of cardiac ischemia
              • No consistent evidence that concurrent aspirin mitigates CV risk associated with NSAID use; concurrent aspirin and NSAID increases risk of serious gastrointestinal (GI) events
              • Increased risk of serious cardiovascular (CV) thrombotic events, including MI and stroke associated with COX-2 selective and nonselective NSAIDs
              • Based on available data, it is unclear that risk for CV events is similar for all NSAIDs
              • Relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease
              • However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, owing to their increased baseline rate
              • Minimize potential risk by prescribing lowest effective dose for the shortest duration possible

              GI bleeding, ulceration, and perforation

              • NSAIDs can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal
              • Risk factors include
                • History of peptic ulcer disease and/or GI bleeding with NSAIDs (>10-fold increased risk compared with patients without these risk factors)
                • Longer duration of NSAID therapy
                • Concomitant use of oral corticosteroids, aspirin, anticoagulants, or SSRIs
                • Smoking
                • Use of alcohol
                • Older age
                • Poor general health status
              • Strategies to decrease GI risks with NSAIDs
                • Use lowest effective dosage for shortest possible duration
                • Avoid using more than 1 NSAID at a time
                • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased bleeding risk (consider alternant therapies)
                • Monitor for signs and symptoms of GI ulcerations and bleeding during NSAID therapy
                • If serious GI adverse event suspected, promptly initiate additional evaluation and treatment, and discontinue NSAID until GI adverse ruled out
                • In low-dose aspirin is concomitantly used for cardiac prophylaxis, monitor more closely for evidence of GI bleeding

              Hypertension

              • NSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events
              • Patients taking ACE inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs
              • Monitor BP during initiation and during treatment

              Heart failure and edema

              • Meta-analysis of randomized controlled trials demonstrated ~2-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared with placebo
              • Additionally, fluid retention and edema observed in some patients treated with NSAIDs Ibuprofen may blunt CV effects of several therapeutic agents (eg, diuretics, ACE inhibitors or angiotensin receptor blockers [ARBs])
              • Avoid with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure

              Renal toxicity and hyperkalemia

              • Renal toxicity
                • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury
                • Renal toxicity also reported in patients in whom renal prostaglandins have a compensatory role to maintain renal perfusion; NSAIDs may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation
                • Patients at greatest risk include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and elderly individuals
              • Hyperkalemia
                • Increased serum potassium concentration, including hyperkalemia, reported with NSAIDs, even in some patients without renal impairment
                • In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state

              Anaphylaxis and other hypersensitivity reactions

              • Acetaminophen
                • Post-marketing reports of hypersensitivity and anaphylaxis
                • Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting
              • Ibuprofen
                • Anaphylactic reactions reported in patients with and without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma

              Exacerbation of asthma related to aspirin sensitivity

              • Subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs
              • Because cross-reactivity between aspirin and other NSAIDs reported in such aspirin-sensitive patients, acetaminophen/ibuprofen is contraindicated in patients with this form of aspirin sensitivity

              Serious skin reactions

              • Acetaminophen or NSAIDs may cause serious skin adverse events (eg, exfoliative dermatitis, acute generalized exanthematous pustulosis [AGEP], Stevens-Johnson Syndrome [SJS], and toxic epidermal necrolysis [TEN], which can be fatal
              • These serious reactions may occur without warning
              • Inform patients about signs and symptoms of serious skin reactions and to discontinue acetaminophen/ibuprofen at the first appearance of skin rash or any other sign of hypersensitivity
              • DRESS
                • Drug rash with eosinophilia and systemic symptoms (DRESS) reported with NSAIDs Some of these events have been fatal or life-threatening
                • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
                • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis
                • Additionally, eosinophilia is often present

              Fetal toxicity

              • Premature closure of fetal ductus arteriosus
                • Avoid NSAIDs in pregnant females at ~30 weeks gestation and later
                • NSAID-containing products increase risk of premature closure of the fetal ductus arteriosus at approximately this gestational age
              • Oligohydramnios/neonatal renal impairment
                • Use of NSAID-containing products at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
                • Oligohydramnios is often, but not always, reversible with treatment discontinuation
                • Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation

              Hematologic toxicity

              • Anemia reported in NSAID-treated patients
              • This may be due to occult or gross GI blood loss, fluid retention, or an incompletely described effect upon erythropoiesis
              • Owing to the increased risk of GI bleeding with NSAIDs, anemia further increases this risk

              Ophthalmic effects

              • Blurred and/or diminished vision, scotomata, and/or changes in color vision reported inpatients receiving ibuprofen

              Aseptic meningitis

              • Aseptic meningitis with fever and coma observed on rare occasions in patients on ibuprofen therapy
              • More likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases but, it has been reported in patients who do not have an underlying chronic disease

              Masking inflammation and fever

              • Pharmacological activity of reducing inflammation, and possibly fever, may diminish utility of diagnostic signs in detecting infections

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              Pregnancy & Lactation

              Pregnancy

              Ibuprofen

              • Use of NSAID-containing products can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
              • Because of these risks, limit dose and duration of use between ~20-30 weeks of gestation and avoid use at ~30 weeks of gestation and later in pregnancy

              Acetaminophen

              • Low risk of cryptorchidism in boys if used for several weeks or longer

              Lactation

              Ibuprofen

              • Considered compatible with breastfeeding (LactMed)
              • No lactation studies have been conducted; however, limited published literature reports that following oral administration, ibuprofen is present in human milk at relative infant doses of 0.06-0.6% of the maternal weight-adjusted daily dose

              Acetaminophen

              • Considered compatible with breastfeeding (LactMed)

              Pregnancy Categories

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

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

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

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

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

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Acetaminophen

              • Acts on hypothalamus to produce antipyresis
              • May work peripherally to block pain impulse generation; may also inhibit prostaglandin synthesis in CNS

              Ibuprofen

              • Elicits anti-inflammatory, analgesic, and antipyretic activity
              • Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2
              • May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to its anti-inflammatory activity

              Absorption (Combogesic)

              Peak plasma time: 0.75-1.25 hr

              Peak plasma concentration

              • Acetaminophen: 14.88 mcg/mL
              • Ibuprofen: 25.58 mcg/mL

              AUC

              • Acetaminophen: 47.44 mcg⋅hr/mL
              • Ibuprofen: 95.62 mcg⋅hr/mL

              Effects of food

              • Acetaminophen: Peak plasma concentration delayed by ~30 min and reduced by ~30% (extent of absorption the same)
              • Ibuprofen: Peak plasma time and concentration were not affected by food

              Distribution

              Acetaminophen

              • Protein bound: ~20%
              • Vd: 0.9 L/kg; widely distributed throughout most tissues except fat

              Metabolism

              Ibuprofen: Rapidly metabolized and eliminated in urine

              Acetaminophen

              • Eliminated by formation of glucuronide and sulfate conjugates in a dose-dependent manner
              • Primarily metabolized in liver by
                • Conjugation with glucuronide
                • Conjugation with sulfate
                • Oxidation via CYP450-dependent, mixed-function oxidase enzyme pathway to form reactive intermediate metabolite, which conjugates with glutathione and then further metabolized to form cysteine and mercapturic acid conjugates
                • Principle P450 isoenzymes involved include CYP2E1, with CYP1A2 and CYP3A4 as additional pathways

              Elimination

              Half-life

              • Acetaminophen: 2-3 hr (adults); somewhat shorter in children and somewhat longer in neonates and patients with cirrhosis
              • Ibuprofen: 1.9-2.2 hr

              Excretion

              • Acetaminophen: <9% excreted unchanged in urine
              • Ibuprofen: Urine 45-79% (metabolite), ~1% (free), and ~14% (conjugated)
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              Administration

              Oral Administration

              Take with food or milk if GI distress occurs

              Storage

              Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86º); avoid excessive heat >40ºC (104ºF)

              Protect from moisture and light

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              Patient Handout

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              Formulary

              FormularyPatient Discounts

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.