diflunisal (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 500mg

Pain

500-1000 mg PO first dose, THEN

250-500 mg PO q8-12hr; not to exceed 1.5 g/day

Osteoarthritis

500-1000 mg PO daily divided q12hr

Maximum dose: 1500 mg/day

Rheumatoid Arthritis

500-1000 mg PO daily divided q12hr

Maximum dose: 1500 mg/day

Renal Impairment

Initiate at lower dose, monitor for ADRs

CrCl<50 mL/min: 50% of regular dose

Hepatic Impairment

Initiate at lower dose, monitor for ADRs

Administration

Take with food or 8-12 oz water to avoid GI effects

Other Indications & Uses

Off-label: Vascular headache

<12 years old: Safety & efficacy not established

Pain

500-1000 mg PO first dose, THEN

250-500 mg PO q8-12hr; not to exceed 1.5 g/day

Osteoarthritis

500-1000 mg PO daily divided q12hr

Maximum dose: 1500 mg/day

Rheumatoid Arthritis

500-1000 mg PO daily divided q12hr

Maximum dose: 1500 mg/day

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Interactions

Interaction Checker

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              Serious - Use Alternative (21)

              • aminolevulinic acid oral

                aminolevulinic acid oral, diflunisal. 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

                diflunisal, 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.

              • baricitinib

                diflunisal will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.

              • benazepril

                diflunisal, 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

                diflunisal, 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

                diflunisal, 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

                diflunisal, 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

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

              • ketorolac intranasal

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

              • lisinopril

                diflunisal, 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.

              • measles, mumps, rubella and varicella vaccine, live

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

              • methotrexate

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

              • methyl aminolevulinate

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

              • moexipril

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

              • pemetrexed

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

              • perindopril

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

              • quinapril

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

              • ramipril

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

              • tacrolimus

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

              • trandolapril

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

              • varicella virus vaccine live

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

              Monitor Closely (238)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

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

              • acetazolamide

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

                acetazolamide, diflunisal. Mechanism: passive renal tubular reabsorption due to increased pH. Use Caution/Monitor. Salicylate levels increased at moderate doses; risk of CNS toxicity. Salicylate levels decreased at large doses (d/t increased renal excretion of unchanged salicylic acid).

              • agrimony

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

              • albuterol

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

              • alfalfa

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

              • alfuzosin

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

              • aliskiren

                diflunisal 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

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

              • American ginseng

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

              • amiloride

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

              • antithrombin alfa

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

                diflunisal increases effects of antithrombin alfa by plasma protein binding competition. Use Caution/Monitor.

              • antithrombin III

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

                diflunisal increases effects of antithrombin III by plasma protein binding competition. Use Caution/Monitor.

              • arformoterol

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

              • argatroban

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

                diflunisal increases effects of argatroban by plasma protein binding competition. Use Caution/Monitor.

              • artesunate

                diflunisal will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.

              • asenapine

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

              • aspirin

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

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

              • aspirin rectal

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

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

              • aspirin/citric acid/sodium bicarbonate

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

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

              • atenolol

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

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

              • azilsartan

                diflunisal, 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.

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

              • bemiparin

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

                diflunisal increases effects of bemiparin by plasma protein binding competition. Use Caution/Monitor.

              • benazepril

                benazepril, diflunisal. 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

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

              • betaxolol

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

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

              • betrixaban

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

              • bimatoprost

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

              • bisoprolol

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

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

              • bivalirudin

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

                diflunisal increases effects of bivalirudin by plasma protein binding competition. Use Caution/Monitor.

              • brinzolamide

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

              • budesonide

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

              • bumetanide

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

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

              • candesartan

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

                diflunisal 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, diflunisal. 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, diflunisal. 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.

              • carbenoxolone

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

              • carvedilol

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

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

              • celecoxib

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

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

              • celiprolol

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

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

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

              • cinnamon

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

              • ciprofloxacin

                diflunisal, 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, diflunisal. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

              • clobetasone

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

              • clomipramine

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

              • cordyceps

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

              • cortisone

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

              • cyclopenthiazide

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

              • cyclosporine

                diflunisal, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Potential for dangerous interaction. Use with caution and monitor closely.

              • dabigatran

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

                diflunisal increases effects of dabigatran by plasma protein binding competition. Use Caution/Monitor.

              • dalteparin

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

                diflunisal increases effects of dalteparin by plasma protein binding competition. Use Caution/Monitor.

              • deferasirox

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

              • defibrotide

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

              • deflazacort

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

              • dexamethasone

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

              • diclofenac

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

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

              • digoxin

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

              • dobutamine

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

              • dong quai

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

              • dopexamine

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

              • doxazosin

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

              • drospirenone

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

              • duloxetine

                duloxetine, diflunisal. 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, diflunisal. 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.

              • eltrombopag

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

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF, diflunisal. 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, diflunisal. 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, diflunisal. 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 diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.

                diflunisal increases effects of enoxaparin by plasma protein binding competition. Use Caution/Monitor.

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • eprosartan

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

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

              • esmolol

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

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

              • ethacrynic acid

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

              • etodolac

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

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

              • fenbufen

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

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

              • fennel

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

              • fenoprofen

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

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

              • feverfew

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

              • fish oil triglycerides

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

              • fludrocortisone

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

              • fluoxetine

                fluoxetine, diflunisal. 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

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

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

              • fluvoxamine

                fluvoxamine, diflunisal. 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 diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.

                diflunisal increases effects of fondaparinux by plasma protein binding competition. Use Caution/Monitor.

              • formoterol

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

              • forskolin

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

              • fosinopril

                fosinopril, diflunisal. 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

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

              • garlic

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

              • gemifloxacin

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

              • gentamicin

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

              • ginger

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

              • ginkgo biloba

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

              • green tea

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

              • griseofulvin

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

              • heparin

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

                diflunisal increases effects of heparin by plasma protein binding competition. Use Caution/Monitor.

              • horse chestnut seed

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

              • hyaluronidase

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

              • hydralazine

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

              • hydrochlorothiazide

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

              • hydrocortisone

                diflunisal, 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 diflunisal by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

              • ibuprofen

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

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

              • ibuprofen IV

                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.

              • imatinib

                imatinib, diflunisal. 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.

              • indapamide

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

              • indomethacin

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

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

              • irbesartan

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

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

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

              • isoproterenol

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

              • ketoprofen

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

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

              • ketorolac

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

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

              • ketorolac intranasal

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

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

              • labetalol

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

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

              • latanoprost

                latanoprost, diflunisal. 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, diflunisal. 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).

              • levalbuterol

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

              • levofloxacin

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

              • levomilnacipran

                levomilnacipran, diflunisal. 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.

              • lisinopril

                lisinopril, diflunisal. 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

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

              • lornoxicam

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

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

              • losartan

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

                diflunisal 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, diflunisal. 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.

              • meclofenamate

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

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

              • mefenamic acid

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

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

              • melatonin

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

              • meloxicam

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

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

              • mesalamine

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

              • metaproterenol

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

              • methazolamide

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • metoprolol

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

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

              • milnacipran

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

              • mistletoe

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

              • moexipril

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

              • moxisylyte

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

              • mycophenolate

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

              • nabumetone

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

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

              • nadolol

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

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

              • naproxen

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

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

              • nebivolol

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

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

              • nefazodone

                nefazodone, diflunisal. 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

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

              • norepinephrine

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

              • olmesartan

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

                diflunisal 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, diflunisal. 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.

              • oxaprozin

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

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

              • panax ginseng

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

              • parecoxib

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

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

              • paroxetine

                paroxetine, diflunisal. 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

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

              • pegaspargase

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

              • penbutolol

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

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

              • perindopril

                perindopril, diflunisal. 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 diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.

                diflunisal increases effects of phenindione by plasma protein binding competition. Use Caution/Monitor.

              • phenoxybenzamine

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

              • phentolamine

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

              • phytoestrogens

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

              • pindolol

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

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

              • pirbuterol

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

              • piroxicam

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

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

              • pivmecillinam

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

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • potassium iodide

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

              • pralatrexate

                diflunisal 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

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

              • prazosin

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

              • prednisolone

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

              • prednisone

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

              • probenecid

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

                diflunisal decreases effects of probenecid by unknown mechanism. Use Caution/Monitor.

              • propranolol

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

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

              • protamine

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

                diflunisal increases effects of protamine by plasma protein binding competition. Use Caution/Monitor.

              • quinapril

                quinapril, diflunisal. 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, diflunisal. 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

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

              • reteplase

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

              • rivastigmine

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

              • sacubitril/valsartan

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

                sacubitril/valsartan, diflunisal. 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.

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

              • salicylates (non-asa)

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

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

              • salmeterol

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

              • salsalate

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

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

              • saw palmetto

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

              • sertraline

                sertraline, diflunisal. 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

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

              • silodosin

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

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

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

              • sodium sulfate/potassium sulfate/magnesium sulfate

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

              • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

                diflunisal, sodium sulfate/potassium sulfate/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.

              • sotalol

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

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

              • spironolactone

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

              • succinylcholine

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

              • sulfasalazine

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

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

              • sulindac

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

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

              • tafluprost

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

              • telmisartan

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

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

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

              • tenecteplase

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

              • tenofovir DF

                tenofovir DF, diflunisal. 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

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

              • terbutaline

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

              • ticarcillin

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

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

              • timolol

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

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

              • tobramycin inhaled

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

              • tolazamide

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

              • tolbutamide

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

              • tolfenamic acid

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

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

              • tolmetin

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

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

              • tolvaptan

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

              • torsemide

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

              • trandolapril

                trandolapril, diflunisal. 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, diflunisal. 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, diflunisal. 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

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

              • triamterene

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

              • valsartan

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

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

              • voclosporin

                voclosporin, diflunisal. 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

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

              • vortioxetine

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

              • warfarin

                warfarin and diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.

                diflunisal increases effects of warfarin by plasma protein binding competition. Use Caution/Monitor.

              • zanubrutinib

                diflunisal, 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

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

              Minor (111)

              • aceclofenac

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

              • acemetacin

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

              • acyclovir

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

              • alendronate

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

              • aluminum hydroxide

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

              • amikacin

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

              • aminohippurate sodium

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

              • anamu

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

              • ascorbic acid

                diflunisal decreases levels of ascorbic acid by increasing renal clearance. Minor/Significance Unknown.

              • aspirin

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

              • aspirin rectal

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

              • aspirin/citric acid/sodium bicarbonate

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

              • balsalazide

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

              • bendroflumethiazide

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

              • budesonide

                budesonide decreases levels of diflunisal by increasing renal clearance. Minor/Significance Unknown.

              • bumetanide

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

              • calcium carbonate

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

              • cefadroxil

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

              • cefamandole

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

              • cefpirome

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

              • celecoxib

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

              • cephalexin

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

              • chlorothiazide

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

              • chlorpropamide

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

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

              • cortisone

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

              • creatine

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

              • cyanocobalamin

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

              • cyclopenthiazide

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

              • danshen

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

              • deflazacort

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

              • devil's claw

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

              • dexamethasone

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

              • diclofenac

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

              • diclofenac topical

                diclofenac topical, diflunisal. 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.

              • entecavir

                diflunisal, entecavir. Either increases levels of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

              • eplerenone

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

              • ethanol

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

              • etodolac

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

              • fenbufen

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

              • fenoprofen

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

              • feverfew

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

              • fludrocortisone

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

              • flurbiprofen

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

              • folic acid

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

              • furosemide

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

              • ganciclovir

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

              • gentamicin

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

              • hydrochlorothiazide

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

              • hydrocortisone

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

              • ibuprofen

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

              • imidapril

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

              • indapamide

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

              • indomethacin

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

              • insulin aspart

                diflunisal increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin detemir

                diflunisal increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin glargine

                diflunisal increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin glulisine

                diflunisal increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin lispro

                diflunisal increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin NPH

                diflunisal increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • insulin regular human

                diflunisal increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown. Large dose of salicylate.

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • L-methylfolate

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

              • lornoxicam

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

              • meclofenamate

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

              • mefenamic acid

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

              • meloxicam

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

              • mesalamine

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • nabumetone

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

              • naproxen

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

              • neomycin PO

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

              • noni juice

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

              • ofloxacin

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

              • oxaprozin

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

              • parecoxib

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

              • paromomycin

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

              • piroxicam

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

              • prednisolone

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

              • prednisone

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

              • rose hips

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

                diflunisal decreases levels of rose hips by increasing renal clearance. Minor/Significance Unknown.

                rose hips increases levels of diflunisal by decreasing renal clearance. Minor/Significance Unknown.

              • salicylates (non-asa)

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

              • salsalate

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

              • sodium bicarbonate

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

              • sodium citrate/citric acid

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

              • streptomycin

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

              • sulfadiazine

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

              • sulfamethoxazole

                diflunisal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

              • sulfasalazine

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

              • sulfisoxazole

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

              • sulindac

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

              • teniposide

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

              • tobramycin

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

              • tolazamide

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

              • tolbutamide

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

              • tolfenamic acid

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

              • tolmetin

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

              • triamcinolone acetonide injectable suspension

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

              • triamterene

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

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

              • valganciclovir

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

              • vancomycin

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

              • verapamil

                verapamil increases effects of diflunisal by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

              • willow bark

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

                willow bark increases effects of diflunisal by pharmacodynamic synergism. Minor/Significance Unknown. Willow bark contains salicylic acid, which may have additive effects/toxicity with salicylate drugs.

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              Adverse Effects

              >10%

              Increased liver function test (up to 15%)

              1-10%

              Body fluid retention

              Rash

              Abdominal pain

              Constipation

              Diarrhea

              Flatulence

              Indigestion

              Nausea

              Dizziness

              Headache

              Insomnia

              Tinnitus

              <1%

              Edema (<1%)

              Hypertension

              Myocardial infarction

              Vasculitis (<1%)

              Erythema multiforme (<1%)

              Scaling eczema, Stevens-Johnson syndrome (<1%)

              Toxic epidermal necrolysis (<1%)

              Gastrointestinal hemorrhage (<1%)

              Gastrointestinal perforation (<1%)

              Inflammatory disorder of digestive tract

              Agranulocytosis (<1%)

              Anemia (<1%)

              Thrombocytopenia (<1%)

              Hepatitis (<1%)

              Jaundice (<1%)

              Anaphylactoid reaction (<1%)

              Immune hypersensitivity reaction (<1%)

              Cerebrovascular accident

              Impaired renal function disorder (<1%)

              Interstitial nephritis (<1%)

              Renal failure (<1%)

              Bronchospasm

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              Warnings

              Black Box Warnings

              Cardiovascular Risk

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

              Gastrointestinal Risk

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

              Contraindications

              Absolute: hypersensitivity to diflunisal, ASA allergy, history of aspirin triad, CABG

              Relative: bleeding disorders, duodenal/gastric/peptic ulcer, renal impairment, stomatitis, ulcerative colitis, upper GI dz, late pregnancy (risk of premature closure of ductus arteriosus)

              Cautions

              Use caution in bronchospasm, cardiac disease, CHF, hepatic/renal impairment, HTN, SLE, fluid retention, >65 years

              Potential risk of cardiovascular damage

              Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs

              Risk of serious skin reactions

              Heart Failure (HF) risk

              • NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
              • NSAIDS should be avoided or withdrawn whenever possible
              • AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
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              Pregnancy & Lactation

              Pregnancy Category: C (avoid in late pregnancy; may cause premature closure of ductus arteriosus)

              The Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and in approximately 2.6% of controls. (CMAJ, September 6, 2011; DOI:10.1503/cmaj.110454)

              Lactation: enters breast milk/not recommended

              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

              Inhibits cyclooxygenase-1 (COX-1) & -2 (COX-2), thereby inhibiting prostaglandin synthesis

              Pharmcokinetics

              Bioavailability: 80-100%

              Peak Plasma Time: within 2-3 hr

              Protein Bound: at least 98-99%

              Vd: 0.11 L/kg

              Metabolism: Liver (to glucuronide conjugates, not to salicylic acid)

              Metabolites: salicylurate, salicyl phenolic glucuronide, salicyl acyl glucuronide, 2,5-dihydroxybenzoic acid (gentisic acid), 2,3-dihydroxybenzoic acid, 2,3,5-trihydroxybenzoic acid, gentisuric acid (active)

              Enzymes inhibited: Prostaglandin synthesis (insignificant)

              Half-life: 8-12 hr

              Excretion: Urine ~90%; feces <5%

              Renal Clearance: 80-100% in 24-72 hr

              Dialyzable: Yes

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              diflunisal oral
              -
              500 mg tablet
              diflunisal oral
              -
              500 mg tablet

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              Patient Education
              diflunisal oral

              DIFLUNISAL - ORAL

              (dye-FLEW-niss-all)

              COMMON BRAND NAME(S): Dolobid

              WARNING: This drug may rarely cause serious (rarely fatal) bleeding from the stomach or intestines. This side effect can occur without warning at any time during treatment with diflunisal. The elderly are at increased risk for serious stomach/intestinal bleeding.Nonsteroidal anti-inflammatory drugs (including diflunisal) may rarely increase the risk for a heart attack or stroke. This effect can happen at any time while taking this drug but is more likely if you take it for a long time. The risk may be greater if you have heart disease or increased risk for heart disease (for example, due to smoking, family history of heart disease, or conditions such as high blood pressure or diabetes). Do not take this drug right before or after heart bypass surgery (CABG). Talk with your doctor or pharmacist about the risks and benefits of treatment with this medication.Stop taking diflunisal and seek immediate medical attention if you notice any of the following rare but very serious side effects: black stools, persistent stomach/abdominal pain, vomit that looks like coffee grounds, chest pain, shortness of breath, weakness on one side of the body, sudden vision changes, trouble speaking.

              USES: Diflunisal is used to relieve mild to moderate pain from various conditions. It also reduces pain, swelling, and joint stiffness caused by arthritis. Reducing these symptoms helps you do more of your normal daily activities. This medication is known as a nonsteroidal anti-inflammatory drug (NSAID).

              HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using diflunisal and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.Take this medication by mouth with a full glass of water (8 ounces or 240 milliliters) unless your doctor directs you otherwise. Do not lie down for at least 10 minutes after taking this drug. Take this medication with food/milk or right after meals to prevent stomach upset.Swallow this medication whole. Do not crush or chew the tablets. Doing so may increase side effects.Dosage is based on your medical condition and response to therapy. Do not take more than 1,500 milligrams per day. To minimize side effect risks (e.g., stomach bleeding), use this medication at the lowest effective dose for the shortest possible length of time. Do not increase your dose or take it more often than prescribed. For ongoing conditions such as arthritis, continue taking it as directed by your doctor. Discuss the risks and benefits with your doctor or pharmacist.In certain conditions (e.g., arthritis), it may take up to 2 weeks of regular use before the full benefits of this drug take effect.If you are taking this drug on an "as needed" basis (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has significantly worsened, the medicine may not work as well.Inform your doctor if your condition worsens.

              SIDE EFFECTS: See also Warning section.Upset stomach, heartburn, headache, tiredness, drowsiness, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if any of these unlikely but serious side effects occur: stomach pain, vision changes, hearing changes (e.g., ringing in the ears), mental/mood changes (e.g., confusion, hallucinations), fast/pounding heartbeat, persistent/severe headache, fainting, difficult/painful swallowing, symptoms of heart failure (such as swelling ankles/feet, unusual tiredness, unusual/sudden weight gain).Tell your doctor right away if any of these rare but very serious side effects occur: signs of kidney problems (such as change in the amount of urine), easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), unexplained stiff neck.This drug may rarely cause serious (possibly fatal) liver disease. If you notice any of the following rare but very serious side effects, stop taking diflunisal and tell your doctor right away: yellowing eyes/skin, dark urine, unusual/extreme tiredness, severe stomach/abdominal pain, persistent nausea/vomiting.A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: See also Warning section.Before taking diflunisal, tell your doctor or pharmacist if you are allergic to it; or to aspirin or other salicylates (e.g., choline salicylate), or other NSAIDs (e.g., ibuprofen, naproxen, celecoxib); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma (including a history of worsening breathing after taking aspirin or other NSAIDs), liver disease, poorly controlled diabetes, stomach/intestine/esophagus problems (e.g., bleeding, ulcers), heart disease (e.g., history of heart attack), stroke, high blood pressure, swelling (edema, fluid retention), blood disorders (e.g., anemia), bleeding or clotting problems, growths in the nose (nasal polyps).Kidney problems can sometimes occur with the use of NSAID medications, including diflunisal. Problems are more likely to occur if you are dehydrated, have heart failure or kidney disease, are an older adult, or if you take certain medications (see also Drug Interactions section). Drink plenty of fluids as directed by your doctor to prevent dehydration and tell your doctor right away if you have a change in the amount of urine.Before having surgery, tell your doctor or dentist that you are using this medication.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Talk to your doctor if you are using marijuana (cannabis).This medicine may cause stomach bleeding. Daily use of alcohol and tobacco may increase your risk for stomach bleeding, especially when combined with this medicine. Limit alcohol and stop smoking. Consult your doctor or pharmacist for more information.The elderly may be more sensitive to the side effects of this drug, especially stomach/intestinal bleeding and kidney problems.This medication is not recommended for use in children under 12 years of age. In addition, since diflunisal is related to aspirin, children and teenagers younger than 18 years should not take diflunisal if they have chickenpox, influenza, or any undiagnosed illness without first consulting a doctor about Reye's syndrome, a rare but serious illness.Before using this medication, women of childbearing age should talk with their doctor(s) about the benefits and risks. Tell your doctor if you are pregnant or if you plan to become pregnant. This medication may harm an unborn baby and cause problems with normal labor/delivery. It is not recommended for use in pregnancy from 20 weeks until delivery. If your doctor decides that you need to use this medication between 20 and 30 weeks of pregnancy, you should use the lowest effective dose for the shortest possible time. You should not use this medication after 30 weeks of pregnancy.This drug passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

              DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: aliskiren, ACE inhibitors (such as captopril, lisinopril), angiotensin II receptor blockers (such as losartan, valsartan), antacids (regular use), cidofovir, corticosteroids (e.g., prednisone), digoxin, live influenza vaccine, lithium, methotrexate, pemetrexed, probenecid, "water pills" (diuretics such as furosemide, hydrochlorothiazide, triamterene).This medication may increase the risk of bleeding when taken with other drugs that also may cause bleeding. Examples include anti-platelet drugs such as clopidogrel, "blood thinners" such as dabigatran/enoxaparin/warfarin, among others.Check all prescription and nonprescription medicine labels carefully since many contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, indomethacin, ketorolac or naproxen) which if taken together with diflunisal may increase your risk for side effects. Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually 81-162 milligrams a day), should be continued. Consult your doctor or pharmacist for more details.This medication can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include severe stomach pain, vomit that looks like coffee grounds, extreme drowsiness, fast breathing, confusion, loss of consciousness.

              NOTES: Do not share this medication with others.Laboratory and/or medical tests (e.g., complete blood count, liver and kidney function tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.Non-drug treatment for arthritis that is approved by your doctor (e.g., weight loss if needed, strengthening and conditioning exercises) may help improve your flexibility, range of motion, and joint function. Consult your doctor for specific instructions.

              MISSED DOSE: If you are prescribed this drug on a regular schedule (not just "as needed") and you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

              Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

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

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.