acetaminophen IV/ibuprofen IV (Rx)

Brand and Other Names:Combogesic IV

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

acetaminophen/ibuprofen

injectable solution

  • (1,000mg/300mg)/10mL (ie, [10mg/3mg]/mL) single-dose vial

Pain

Indicated for mild-to-moderate pain and for management of moderate-to-severe pain as an adjunct to opioid analgesics in adults, where an IV route of administration is considered clinically necessary

Dosage based on actual body weight

  • ≥50 kg
    • 1,000 mg/300 mg (100 mL [1 vial]) IV q6hr prn
    • Not to exceed total daily dose of 4,000 mg acetaminophen and 1,200 mg ibuprofen
  • <50 kg
    • 15 mg/kg acetaminophen and 4.5 mg/kg ibuprofen IV q6hr prn
    • Not to exceed single dose of 750 mg acetaminophen and 225 ibuprofen
    • Not to exceed total daily dose of 3,000 mg acetaminophen and 900 mg ibuprofen

Dosage Modifications

Renal impairment

  • Any severity: Not recommended

Hepatic impairment

  • Mild-to-moderate: Not recommended
  • Severe impairment of severe active liver disease: Contraindicated

Dosing Considerations

Limitation of use: Indicated for short-term use (ie, ≤5 days)

Use lowest effective dosage for shortest duration consistent with individual patient treatment goals

Do not coadminister with other acetaminophen or ibuprofen containing products

Consider all sources of acetaminophen and ibuprofen when calculating total daily dose

Safety and efficacy not established

Pain

Indicated for mild-to-moderate pain and for management of moderate-to-severe pain as an adjunct to opioid analgesics in adults, where an IV route of administration is considered clinically necessary

Dosage based on actual body weight

  • ≥50 kg
    • 1,000 mg/300 mg (100 mL [1 vial]) IV q6hr prn
    • Not to exceed total daily dose of 4,000 mg acetaminophen and 1,200 mg ibuprofen
  • <50 kg
    • 15 mg/kg acetaminophen and 4.5 mg/kg ibuprofen IV q6hr prn
    • Not to exceed single dose of 750 mg acetaminophen and 225 ibuprofen
    • Not to exceed total daily dose of 3,000 mg acetaminophen and 900 mg ibuprofen

Dosage Modifications

Renal impairment

  • Any severity: Not recommended

Hepatic impairment

  • Mild-to-moderate: Not recommended
  • Severe impairment of severe active liver disease: Contraindicated

Dosing Considerations

Limitation of use: Indicated for short-term use (ie, ≤5 days)

Use lowest effective dosage for shortest duration consistent with individual patient treatment goals

Do not coadminister with other acetaminophen or ibuprofen containing products

Consider all sources of acetaminophen and ibuprofen when calculating total daily dose

Geriatric use

  • Compared to younger patients, geriatric patients are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions
  • If anticipated benefit for patient outweighs these potential risks, start dosing at lowest end of dosing range, and monitor for adverse effects
  • Ibuprofen and acetaminophen are substantially excreted renally, and risk of adverse effects may be greater in patients with renal impairment
  • Geriatric patients are more likely to have decreased renal function; carefully select dose and monitor renal function
Next:

Interactions

Interaction Checker

and acetaminophen IV/ibuprofen IV

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              Serious - Use Alternative (15)

              • aminolevulinic acid oral

                aminolevulinic acid oral, ibuprofen IV. 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 IV, 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 IV and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

              • aspirin

                ibuprofen IV increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

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

              • aspirin rectal

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

              • fosinopril

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

              • ketorolac intranasal

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

              • lisinopril

                ibuprofen IV, 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 IV 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.

              • meclofenamate

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

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

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

              Monitor Closely (266)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

              • agrimony

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

              • albuterol

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

              • alfalfa

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

              • alfuzosin

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

              • aliskiren

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

              • American ginseng

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

              • amikacin

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

              • amiloride

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

              • antithrombin alfa

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

              • antithrombin III

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

              • arformoterol

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

              • argatroban

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

              • asenapine

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

              • aspirin

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

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

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

              • aspirin rectal

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

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

                aspirin rectal and ibuprofen IV both increase serum potassium. Modify Therapy/Monitor Closely.

              • aspirin/citric acid/sodium bicarbonate

                aspirin/citric acid/sodium bicarbonate will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

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

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

              • atenolol

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

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

              • atogepant

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

              • avapritinib

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

              • axitinib

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

              • azficel-T

                azficel-T, ibuprofen IV. 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 IV, 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 IV 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.

              • benazepril

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

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

              • betaxolol

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

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

              • betrixaban

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

              • bimatoprost

                bimatoprost, ibuprofen IV. 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

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

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

              • bivalirudin

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

              • budesonide

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

              • bumetanide

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

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

              • busulfan

                acetaminophen IV 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

                ibuprofen IV decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

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

              • carvedilol

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

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

              • celecoxib

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

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

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

              • celiprolol

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

              • chlorothiazide

                ibuprofen IV increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

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

              • chlorpropamide

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

              • chlorthalidone

                ibuprofen IV increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

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

              • choline magnesium trisalicylate

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

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

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

              • cinnamon

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

              • ciprofloxacin

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

              • cordyceps

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

              • cortisone

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

              • cyclopenthiazide

                ibuprofen IV increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

              • cyclosporine

                ibuprofen IV increases toxicity of cyclosporine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

              • dabigatran

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

              • deferasirox

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

              • defibrotide

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

              • deflazacort

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

              • dexamethasone

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

              • dichlorphenamide

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

              • diclofenac

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

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

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

              • diflunisal

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

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

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

              • digoxin

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

              • dobutamine

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

              • dong quai

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

              • doxazosin

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

              • dronabinol

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

              • duloxetine

                duloxetine, ibuprofen IV. 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 IV. 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              • eltrombopag

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

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

              • eluxadoline

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

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • eprosartan

                ibuprofen IV decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

                eprosartan, ibuprofen IV. 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 IV. 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

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

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

              • ethacrynic acid

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

              • etodolac

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

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

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

              • exenatide injectable suspension

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

              • felbamate

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

              • fennel

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

              • fenoprofen

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

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

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

              • feverfew

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

              • finerenone

                acetaminophen IV 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 IV 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 IV 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 IV, 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

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

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

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

              • fluvoxamine

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

              • fondaparinux

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

              • formoterol

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

              • forskolin

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

              • fosinopril

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

              • garlic

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

              • gemifloxacin

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

              • gentamicin

                ibuprofen IV increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease excretion of aminoglycosides; data only on premature infants.

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

              • ginger

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

              • ginkgo biloba

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

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

              • green tea

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

              • heparin

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

              • horse chestnut seed

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

              • hydralazine

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

              • hydrochlorothiazide

                ibuprofen IV increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

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

              • hydrocortisone

                ibuprofen IV, 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 IV 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.

              • icosapent

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

              • imatinib

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

                imatinib, ibuprofen IV. 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 decreases levels of acetaminophen IV 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.

              • indapamide

                ibuprofen IV increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

              • isavuconazonium sulfate

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

              • indomethacin

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

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

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

              • irbesartan

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

                irbesartan, ibuprofen IV. 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 IV by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

              • isoproterenol

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

              • ivacaftor

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

              • ketoprofen

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

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

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

              • ketorolac

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

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

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

              • ketorolac intranasal

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

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

              • labetalol

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

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

              • lacosamide

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

              • levalbuterol

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

              • levofloxacin

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

              • levomilnacipran

                levomilnacipran, ibuprofen IV. 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 IV by unknown mechanism. Use Caution/Monitor.

              • lisinopril

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

              • lomitapide

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

              • losartan

                ibuprofen IV decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

                losartan, ibuprofen IV. 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

              • mefenamic acid

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

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

              • melatonin

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

              • meloxicam

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

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

              • mesalamine

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

              • metaproterenol

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

              • methotrexate

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • metoprolol

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

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

              • midazolam intranasal

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

              • tazemetostat

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

              • moexipril

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

              • moxisylyte

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

              • mycophenolate

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

              • nabumetone

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

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

              • nadolol

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

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

              • nafcillin

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

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

              • nebivolol

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

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

              • nefazodone

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

              • norepinephrine

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

              • ofloxacin

                ofloxacin, ibuprofen IV. Other (see comment). Use Caution/Monitor. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

              • olmesartan

                ibuprofen IV decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

                olmesartan, ibuprofen IV. 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.

              • oxacillin

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

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

              • panax ginseng

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

              • paroxetine

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

              • pegaspargase

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

              • peginterferon alfa 2b

                peginterferon alfa 2b decreases levels of ibuprofen IV 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

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

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

              • penicillin G aqueous

                penicillin G aqueous, ibuprofen IV. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

                penicillin G aqueous, ibuprofen IV. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              • penicillin VK

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

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

              • perindopril

                perindopril, ibuprofen IV. 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 IV both increase anticoagulation. Modify Therapy/Monitor Closely.

              • phenoxybenzamine

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

              • phentolamine

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

              • phytoestrogens

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

              • pindolol

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

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

              • pirbuterol

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

              • piroxicam

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

                ibuprofen IV and piroxicam both increase anticoagulation. Use Caution/Monitor. Therapeutic duplication

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

              • pivmecillinam

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • potassium iodide

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

              • pralatrexate

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

              • prazosin

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

              • prednisolone

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

              • prednisone

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

              • probenecid

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

              • propranolol

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

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

              • protamine

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

              • quinapril

                quinapril, ibuprofen IV. 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 IV. 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 IV and reishi both increase anticoagulation. Use Caution/Monitor.

              • reteplase

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

              • rivaroxaban

                rivaroxaban, ibuprofen IV. 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 IV by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

              • sacubitril/valsartan

                ibuprofen IV decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

                sacubitril/valsartan, ibuprofen IV. 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.

              • salicylates (non-asa)

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

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

              • salmeterol

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

              • salsalate

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

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

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

              • saw palmetto

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

              • sertraline

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

              • silodosin

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

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

                ibuprofen IV, 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 IV 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 IV, 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 IV 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

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

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

              • sparsentan

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

              • succinylcholine

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

              • sulfasalazine

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

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

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

              • sulindac

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

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

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

              • tafluprost

                tafluprost, ibuprofen IV. 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

                ibuprofen IV decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

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

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

              • tenecteplase

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

              • tenofovir DF

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

              • terbutaline

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

              • tetracaine

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

              • ticagrelor

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

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

              • ticlopidine

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

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

              • timolol

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

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

              • tinidazole

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

              • tobramycin inhaled

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

              • tolazamide

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

              • tolbutamide

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

              • tolfenamic acid

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

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

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

              • tolmetin

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

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

              • tolvaptan

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

              • torsemide

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

              • trandolapril

                ibuprofen IV decreases effects of trandolapril by pharmacodynamic synergism. Modify Therapy/Monitor Closely. NSAIDs decrease sysnthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertenisve effect.

                trandolapril, ibuprofen IV. 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 IV. 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 IV. 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 IV, 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, ibuprofen IV. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.

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

              • valoctocogene roxaparvovec

                ibuprofen IV 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

                ibuprofen IV decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

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

              • voclosporin

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

              • vortioxetine

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

              • warfarin

                ibuprofen IV, 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 IV increases effects of warfarin by anticoagulation. Use Caution/Monitor. Likely to occur at doses exceedin 1.3-2 g/day for multiple consecutive days.

              • zanubrutinib

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

              Minor (109)

              • aceclofenac

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

              • acemetacin

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

              • acetazolamide

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

              • acyclovir

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

              • adefovir

                ibuprofen IV 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 IV by unspecified interaction mechanism. Minor/Significance Unknown.

              • alendronate

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

              • aminohippurate sodium

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • amobarbital

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

              • anamu

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

              • antithrombin alfa

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

              • antithrombin III

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

              • argatroban

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

              • balsalazide

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

              • bemiparin

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

              • bivalirudin

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

              • bosentan

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

              • butabarbital

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

              • butalbital

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

              • carbamazepine

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

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

              • chlorpropamide

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

              • cholestyramine

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

              • cimetidine

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

              • clonazepam

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

              • colestipol

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

              • creatine

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

              • dalteparin

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

              • danshen

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

              • devil's claw

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

              • diazepam

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

              • diclofenac topical

                diclofenac topical, ibuprofen IV. 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.

              • digoxin

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

              • disulfiram

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

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

              • enoxaparin

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

              • eplerenone

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

              • ethanol

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

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

              • ethosuximide

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

              • etravirine

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

              • felbamate

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

              • feverfew

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

              • fluconazole

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

              • fondaparinux

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

              • fosphenytoin

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

              • furosemide

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

              • gabapentin

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

              • gabapentin enacarbil

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

              • ganciclovir

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

              • green tea

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

              • heparin

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

              • imidapril

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

              • indapamide

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

              • isoniazid

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

              • ketoconazole

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

              • ketorolac intranasal

                ibuprofen IV 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 IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • lamotrigine

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

              • leflunomide

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

              • levetiracetam

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

              • levoketoconazole

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

              • liraglutide

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

              • lorazepam

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

              • mefenamic acid

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

              • meloxicam

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

              • mesalamine

                ibuprofen IV 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 IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • methyclothiazide

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

              • metoclopramide

                metoclopramide increases levels of acetaminophen IV 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 IV by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • metronidazole

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

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

              • miconazole vaginal

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

              • oxcarbazepine

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

              • nabumetone

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • neomycin PO

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • omeprazole

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

              • oxybutynin

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

              • oxybutynin topical

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

              • oxybutynin transdermal

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

              • paromomycin

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • phenindione

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

              • phenobarbital

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

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

              • phenytoin

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

              • piperacillin

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

              • primidone

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

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

              • protamine

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

              • rifampin

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

              • rifabutin

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

              • rifampin

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

              • rifapentine

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

              • rose hips

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

              • rufinamide

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

              • ruxolitinib

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

              • ruxolitinib topical

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

              • secobarbital

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

              • streptomycin

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

              • tiagabine

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

              • tobramycin

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

              • tolmetin

                ibuprofen IV 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 IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

              • treosulfan

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

              • triamterene

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

              • valganciclovir

                ibuprofen IV 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 IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

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

              • vancomycin

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

              • zonisamide

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

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              Adverse Effects

              >10%

              *Indicates incidence less than acetaminophen or ibuprofen alone

              Infusion site pain (17.6%)

              Nausea (16.3%)*

              1-10%

              *Indicates incidence less than acetaminophen or ibuprofen alone

              Constipation (7.2%)

              Dizziness (7.2%)*

              Infusion site extravasation (6.5%)

              Vomiting (6.2%)*

              Headache (5.5%)*

              Somnolence (3.9%)*

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              Black Box Warnings

              Black Box Warnings

              Medication errors

              • Take care when prescribing, preparing, and administering to avoid dosing errors which could result in accidental overdose and death

              Hepatotoxicity

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

              Cardiovascular risk

              • Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), can increase risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal
              • This risk may occur early in treatment and may increase with duration of use
              • Contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery

              Gastrointestinal (GI) risk

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

              Contraindications

              Hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to acetaminophen, ibuprofen, other NSAIDs or to any other components of this product

              Patients with 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

              Severe hepatic impairment or severe active liver disease

              Cautions

              Risk of medications errors

              • Take care when prescribing, preparing, and administering to avoid dosing errors which could result in accidental overdose and death
              • Ensure that
                • Dose in milligrams (mg) and milliliters (mL) is not confused
                • Dosing is based on weight for patients <50 kg
                • Infusion pumps are properly programmed
                • Total daily dose of acetaminophen from all sources does not exceed maximum daily limits

              Hepatotoxicity

              • Acetaminophen
                • Contains acetaminophen, which has been associated with cases of acute liver failure, at times resulting in liver transplant and death
                • Most cases of liver injury are associated with use of acetaminophen at doses exceeding 4,000 mg/day, and often involve >1 acetaminophen-containing product
                • Risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen
              • Ibuprofen
                • Contains ibuprofen, a NSAID
                • Elevations of ALT or AST (3 x ULN) reported in ~1% of NSAID-treated patients in clinical trials
                • Rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure reported
                • Elevations of ALT or AST (<3 x ULN) may occur in up to 15% of patients treated with NSAIDs, including ibuprofen
              • Clinical recommendations
                • Contraindicated in patients with severe hepatic impairment or severe active liver disease
                • Not been studied in patients with impaired hepatic function
                • Use in these patients is not recommended
                • If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash), discontinue immediately, and clinical evaluate patient

              Cardiovascular thrombotic events

              • Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious CV thrombotic events, including MI and stroke, which can be fatal
              • Unclear if risk for CV thrombotic 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, due to their increased baseline rate
              • Some observational studies found that the increased risk of serious CV thrombotic events began as early as the first weeks of treatment
              • Increase CV thrombotic risk observed most consistently at higher doses
              • Minimize risk by using lowest effective dose for shortest duration possible
              • Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms
              • Inform patients regarding risk of serious CV events and steps to take if they occur
              • There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use
              • Concurrent use of aspirin and NSAIDs increases risk of serious GI events
              • Status post coronary artery bypass graft (CABG) surgery
                • 2 large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10- 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke
                • NSAIDs are contraindicated in the setting of CABG
              • Post-MI patients
                • Danish National Registry observational studies have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment
                • In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients
                • Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next 4 years of follow-up
                • Avoid in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events
                • If used in patients with a recent MI, monitor patients for signs of cardiac ischemia

              Gastrointestinal (GI) bleeding, ulceration, and perforation

              NSAIDs cause serious GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal

              These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs

              Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic

              Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in ~1% of patients treated for 3-6 months and in about 2- 4% of patients treated for 1 year

              However, even short-term therapy is not without risk

              • Risk factors
                • Patients with prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a >10-fold increased risk for developing a GI bleed compared to patients without these risk factors
                • Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or SSRIs; smoking; use of alcohol; older age; and poor general health status
                • Most post-marketing reports of fatal GI events occurred in elderly or debilitated patients
                • Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for getting an ulcer or bleeding
              • Strategies to minimize GI risks in NSAID-treated patients
                • Use lowest effective dosage for shortest possible duration
                • Avoid administering >1 NSAID at a time
                • Avoid use in patients at higher risk, unless benefits are expected to outweigh the increased risk of bleeding; for such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs
                • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
                • If serious GI adverse event suspected, promptly initiate evaluation and treatment, and discontinue acetaminophen/ibuprofen IV until a serious GI adverse event is ruled out
                • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients 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 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 when initiating NSAID treatment and throughout therapy

              Heart failure and edema

              • The Coxib and traditional NSAID Trialists’ Collaboration 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 to placebo-treated patients
              • In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death
              • Additionally, fluid retention and edema observed in some patients treated with NSAIDs
              • Use of ibuprofen may blunt CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, ARBs)
              • Avoid the use with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure
              • If used in patients with severe heart failure, monitor for signs of worsening heart failure

              Renal toxicity and hyperkalemia renal toxicity

              • Renal toxicity
                • Use not recommended in patients with renal impairment
                • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury
                • Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion
                • In these patients, 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 are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and elderly individuals
                • Discontinuation of NSAID therapy is usually followed by recovery to pretreatment status
                • No information is available from controlled clinical studies regarding use of acetaminophen/ibuprofen IV in patients with advanced renal disease
                • Renal effects of acetaminophen/ibuprofen IV may hasten progression of renal dysfunction in patients with pre-existing renal disease
                • Correct volume status in dehydrated or hypovolemic patients before initiating
              • Hyperkalemia
                • Increased serum potassium concentration, including hyperkalemia, reported with NSAIDs, even in some patients without renal impairment
                • With normal renal function, these effects are attributed to a hyporeninemic-hypoaldosteronism state

              Hypersensitivity and anaphylactic reactions

              • Acetaminophen
                • Hypersensitivity and anaphylaxis associated with acetaminophen reported
                • Clinical signs included swelling of face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting
                • There have been rare reports of life-threatening anaphylaxis requiring emergency medical attention
                • Discontinue immediately if symptoms associated with allergy or hypersensitivity occur
                • Do not use in patients with acetaminophen allergy
              • Ibuprofen
                • NSAIDS have been associated with anaphylactic reactions in patients with and without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma
                • Discontinue immediately if symptoms associated with allergy or hypersensitivity occur

              Exacerbation of asthma related to aspirin sensitivity

              • A 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 NSAIDs has been reported in such aspirin-sensitive patients, acetaminophen/ibuprofen IV is contraindicated in patients with this form of aspirin sensitivity
              • When used in patients with preexisting asthma (without known aspirin sensitivity), monitor for changes in signs and symptoms of asthma

              Serious skin reactions

              • Acetaminophen or NSAIDs may cause serious skin reactions such as exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal
              • These serious events may occur without warning
              • Inform patients about signs and symptoms of serious skin reactions
              • Discontinue use at first appearance of skin rash or any other sign of hypersensitivity
              • Contraindicated in patients with previous serious skin reactions to acetaminophen or NSAIDs

              Drug rash with eosinophilia and systemic symptoms (DRESS)

              • DRESS reported in patients taking NSAIDs
              • Some of these events have been fatal or life-threatening
              • DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
              • Other manifestations include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis
              • Sometimes symptoms may resemble an acute viral infection
              • Eosinophilia is often present
              • Because this disorder is variable in its presentation, other organ systems not noted here may be involved
              • It is important to note that early manifestations of hypersensitivity (eg, fever, lymphadenopathy) may be present even though rash is not evident
              • If such signs or symptoms are present, discontinue drug and evaluate patient immediately

              Fetal toxicity

              • Premature closure of fetal ductus arteriosus
                • Avoid use of NSAID-containing products 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 ~20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
                • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hr after NSAID initiation
                • Oligohydramnios is often, but not always, reversible with treatment discontinuation
                • Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation
                • In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required
                • If, after careful consideration of alternative treatment options for pain management, NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit use to the lowest effective dose and shortest duration possible
                • Consider ultrasound monitoring of amniotic fluid if treatment extends >48 hr
                • Discontinue if oligohydramnios occurs and follow up according to clinical practice

              Hematologic toxicity

              • Anemia has occurred in NSAID-treated patients
              • This may be due to occult or gross GI blood loss, fluid retention, or an incompletely described effect on erythropoiesis
              • If signs or symptoms of anemia occur, monitor hemoglobin or hematocrit
              • NSAIDs, including the ibuprofen in COMBOGESIC IV, may increase the risk of bleeding events
              • Comorbid conditions (eg, coagulation disorders, use of warfarin or other anticoagulants, antiplatelet agents [eg, aspirin], SSRIs, SNRIs) may increase this risk
              • Monitor for signs of bleeding

              Ophthalmological effects

              • Blurred or diminished vision, scotomata, and/or changes in color vision reported with oral ibuprofen
              • If such symptoms develop, discontinue drugs consult with an ophthalmologist for examination, including central visual fields and color vision testing

              Aseptic meningitis

              • Aseptic meningitis with fever and coma observed with oral ibuprofen
              • Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have underlying chronic disease
              • If signs or symptoms of meningitis develop, consider possibility of its being related to ibuprofen

              Masking of inflammation and fever

              • The pharmacological activity of acetaminophen/ibuprofen in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections

              Laboratory monitoring

              • Serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs
              • Consider monitoring patients on NSAID treatment with a CBC and a chemistry profile as clinically indicated
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              Pregnancy & Lactation

              Pregnancy

              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 gestation and avoid use at ~30 weeks gestation and later in pregnancy

              Clinical considerations

              • Premature closure of fetal ductus arteriosus
                • Avoid use of NSAID-containing products in females at ~30 weeks gestation and later in pregnancy, because NSAIDs can cause premature closure of the fetal ductus arteriosus
              • Oligohydramnios/neonatal renal impairment
                • If, after consideration of alternative treatments for pain management, an NSAID-containing product is necessary at ~20 weeks gestation or later in pregnancy, limit use to lowest effective dose and shortest duration possible
                • If treatment extends beyond 48 hr, consider monitoring with ultrasound for oligohydramnios
                • If oligohydramnios occurs, discontinue acetaminophen/ibuprofen IV and follow up according to clinical practice
              • Labor or delivery
                • There are no studies on effects of acetaminophen/ibuprofen IV during labor or delivery
                • In animal studies, NSAIDS inhibit prostaglandin synthesis, cause delayed parturition, and increase incidence of stillbirth

              Reproductive potential

              • Acetaminophen
                • Based on animal data, acetaminophen may reduce fertility in males and females of reproductive potential
                • Unknown whether these effects on fertility are reversible
              • Ibuprofen
                • Based on the mechanism of action, prostaglandin-mediated NSAID-containing products may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some females
                • Animal studies have shown that administration of prostaglandin synthesis inhibitors may disrupt prostaglandin mediated follicular rupture required for ovulation
                • Small studies in females treated with NSAIDs have also shown a reversible delay in ovulation
                • Consider withdrawal of NSAID-containing products in females having difficulties conceiving or who are undergoing investigation of infertility

              Lactation

              Ibuprofen and acetaminophen are present in human milk

              Limited published literature reports that, orally administered ibuprofen is present in human milk at relative infant doses of 0.06% to 0.6% of the maternal weight-adjusted daily dose

              There are no reports of adverse effects of ibuprofen on the breastfed infant and no effects on milk production

              Limited published studies report that orally administered acetaminophen passes rapidly into human milk with similar levels in the milk and plasma

              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: Nonopioid analgesic that activates the descending serotonergic inhibitory pathways in the CNS

              Ibuprofen: Nonsteroidal anti-inflammatory with analgesic, antipyretic, and anti-inflammation properties; acts by reversibly inhibiting cyclooxygenase-1 and 2 (COX-1 and COX-2) enzymes resulting in decreased prostaglandin precursor formation

              Fixed-dose combination is an effective alternative to opioid-based analgesics and is thought to be synergistic at managing acute and chronic pain

              Absorption

              Peak plasma time: At end of 15-minute IV infusion

              Peak plasma concentration

              • Acetaminophen: 34.3 mcg/mL
              • Ibuprofen: 48.12 mcg/mL

              AUC

              • Acetaminophen: 56.48 mcg⋅h/mL
              • Ibuprofen: 102.82 mcg⋅h/mL

              Distribution

              Protein bound: ~20% (acetaminophen)

              Vd: 0.9 L/kg (acetaminophen)

              Metabolism

              Acetaminophen

              • Primarily metabolized in liver by first-order kinetics and involving 3 principal separate pathways
                • Conjugation with glucuronide
                • Conjugation with sulfate
                • Oxidation via CYP450-dependent, mixed-function oxidase enzyme pathway to form a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates
                • Principal cytochrome P450 isoenzyme involved is CYP2E1, with CYP1A2 and CYP3A4 as additional pathways

              Elimination

              Half-life

              • Acetaminophen: 2-3 hr
              • Ibuprofen: 1.8-2 hr

              Excretion

              • Acetaminophen: <9% unchanged in urine
              • Ibuprofen: 45-79% recovered urine as metabolites
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              Administration

              IV Preparation

              Visually inspect for particulate matter and discoloration before administration

              Solution should appear clear and colorless, and free from visible particles

              Discard if visibly opaque particles, discoloration, or other foreign particulates observed

              Do not mix with diluents or with other medicines

              Contains no antimicrobial preservative; discard any unused solution

              To decrease bung fragmentation or the bung being forced into the vial, use a syringe or IV set with a diameter <0.8 mm for solution sampling and ensure that the bung is pierced at the location specifically designed for needle introduction (where thickness of the bung is lowest)

              IV Administration

              Infuse IV over 15 minutes

              Do not mix or infuse with other medications

              Storage

              Store at 20-25ºC (68-77ºF); excursions permitted between 15-30ºC (59-86∫F)

              Do not refrigerate or freeze

              Store in original carton to protect from light

              Protect from heat

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              Formulary

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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              Code Definition
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.