diclofenac/misoprostol (Rx)

Brand and Other Names:Arthrotec
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Dosing & Uses

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Dosage Forms & Strengths

diclofenac/misoprostol

tablet

  • 50mg/200mcg
  • 75mg/200mcg

Osteoarthritis

50 mg/200 mcg: 1 tab PO three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

75mg/200mcg: 1 tab PO three times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

If not tolerated, may reduce frequency to twice daily

Three times daily dose of misoprostol is more protective than when given twice daily

Rheumatoid Arthritis

50 mg/200 mcg: 1 tab PO three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

75mg/200mcg: 1 tab PO three or four times daily; not to exceed 200 mcg misoprostol/dose or 800 mcg/day

If not tolerated may reduce frequency to twice daily

Three times daily dose of misoprostol is more protective than when given twice daily

Administration

Swallow tablet whole, do not chew or crush

Do not take with antacids

Safety & efficacy not established

Next:

Interactions

Interaction Checker

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              • aluminum hydroxide/magnesium carbonate

                aluminum hydroxide/magnesium carbonate, misoprostol. unknown mechanism. Avoid or Use Alternate Drug. Antacids reduce the bioavailability of misoprostol acid. Magnesium-containing antacids may potentiate misoprostol-induced diarrhea. If an antacid is needs, use an aluminum- or calcium- containing antacids.

              • aluminum hydroxide/magnesium trisilicate

                aluminum hydroxide/magnesium trisilicate, misoprostol. unknown mechanism. Avoid or Use Alternate Drug. Antacids reduce the bioavailability of misoprostol acid. Magnesium-containing antacids may potentiate misoprostol-induced diarrhea. If an antacid is needs, use an aluminum- or calcium- containing antacids.

              • aminolevulinic acid oral

                aminolevulinic acid oral, diclofenac. 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

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

              • apixaban

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

              • benazepril

                diclofenac, 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

                diclofenac, 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.

              • citric acid/glucono-delta-lactone/magnesium carbonate

                citric acid/glucono-delta-lactone/magnesium carbonate, misoprostol. unknown mechanism. Avoid or Use Alternate Drug. Antacids reduce the bioavailability of misoprostol acid. Magnesium-containing antacids may potentiate misoprostol-induced diarrhea. If an antacid is needs, use an aluminum- or calcium- containing antacids.

              • enalapril

                diclofenac, 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

                diclofenac, 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.

              • ivosidenib

                ivosidenib will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • ketorolac

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

              • ketorolac intranasal

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

              • lisinopril

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

              • lonafarnib

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

              • magnesium gluconate

                magnesium gluconate, misoprostol. unknown mechanism. Avoid or Use Alternate Drug. Antacids reduce the bioavailability of misoprostol acid. Magnesium-containing antacids may potentiate misoprostol-induced diarrhea. If an antacid is needs, use an aluminum- or calcium- containing antacids.

              • methotrexate

                diclofenac 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

                diclofenac, 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

                diclofenac, 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.

              • oxytocin

                misoprostol increases effects of oxytocin by pharmacodynamic synergism. Avoid or Use Alternate Drug. Misoprostol may augment the effects oxytocic agents, especially when given less than 4 hours before initiating oxytocin. .

              • pemetrexed

                diclofenac 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.

              Monitor Closely (267)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

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

              • agrimony

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

              • albuterol

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

              • alfalfa

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

              • alfuzosin

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

              • aliskiren

                diclofenac 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.

              • alpelisib

                alpelisib will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

              • alteplase

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

              • American ginseng

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

              • amiloride

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

              • antithrombin alfa

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

              • antithrombin III

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

              • apalutamide

                apalutamide will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

              • arformoterol

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

              • argatroban

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

              • artesunate

                diclofenac 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

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

              • aspirin

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

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

              • aspirin rectal

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

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

              • aspirin/citric acid/sodium bicarbonate

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

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

              • atazanavir

                atazanavir increases levels of diclofenac by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

              • atenolol

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

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

              • avapritinib

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

              • axitinib

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

              • azficel-T

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

              • azilsartan

                diclofenac, 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.

                diclofenac 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.

                azilsartan decreases effects of diclofenac 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 diclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.

              • benazepril

                benazepril, diclofenac. 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

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

              • betaxolol

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

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

              • betrixaban

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

              • bimatoprost

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

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

              • bivalirudin

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

              • budesonide

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

              • bumetanide

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

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

              • candesartan

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

                diclofenac 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, diclofenac. 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.

              • cannabidiol

                cannabidiol will increase the level or effect of diclofenac by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

              • capecitabine

                capecitabine will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • captopril

                captopril, diclofenac. 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

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

              • carvedilol

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

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

              • celecoxib

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

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

              • celiprolol

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

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • cholestyramine

                cholestyramine decreases levels of diclofenac by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              • choline magnesium trisalicylate

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

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

              • cinnamon

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

              • ciprofloxacin

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

              • clobetasone

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

              • clomipramine

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

              • cordyceps

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

              • cortisone

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

              • cyclopenthiazide

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

              • cyclosporine

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

              • dalteparin

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

              • deferasirox

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

              • deferiprone

                diclofenac will increase the level or effect of deferiprone by decreasing metabolism. Use Caution/Monitor. Coadministration with UGT1A6 inhibitors may increase serum concentration of deferiprone.

              • defibrotide

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

              • deflazacort

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

              • dexamethasone

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

              • diflunisal

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

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

              • digoxin

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

              • dobutamine

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

              • dong quai

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

              • dopexamine

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

              • doxazosin

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

              • drospirenone

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

              • duloxetine

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

              • efavirenz

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

              • eltrombopag

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

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

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

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • eprosartan

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

                diclofenac 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, diclofenac. 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, diclofenac. 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 diclofenac both increase serum potassium. Use Caution/Monitor.

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

              • ethacrynic acid

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

              • etodolac

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

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

              • fenbufen

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

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

              • fennel

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

              • fenoprofen

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

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

              • feverfew

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

              • finerenone

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

              • fish oil triglycerides

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

              • flibanserin

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

              • flucloxacillin

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

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

              • fluconazole

                fluconazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • fludrocortisone

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

              • fluorouracil

                fluorouracil will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • fluoxetine

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

                fluoxetine, diclofenac. 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

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

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

              • fluvoxamine

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

              • formoterol

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

              • forskolin

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

              • fosinopril

                fosinopril, diclofenac. 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

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

              • garlic

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

              • gemfibrozil

                gemfibrozil will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • gemifloxacin

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

              • gentamicin

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

              • ginger

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

              • ginkgo biloba

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

              • green tea

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

              • heparin

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

              • horse chestnut seed

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

              • hydralazine

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

              • hydrochlorothiazide

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

              • hydrocortisone

                diclofenac, 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 diclofenac 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

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

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

              • ibuprofen IV

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

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

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

              • imatinib

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

                imatinib, diclofenac. 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

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

              • indomethacin

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

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

              • irbesartan

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

                diclofenac 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, diclofenac. 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

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

              • ivacaftor

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

              • ketoconazole

                ketoconazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • ketoprofen

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

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

              • ketorolac

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

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

              • ketorolac intranasal

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

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

              • labetalol

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

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

              • latanoprost

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

              • lemborexant

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

              • levalbuterol

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

              • levofloxacin

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

              • levomilnacipran

                levomilnacipran, diclofenac. 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, diclofenac. 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

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

              • lomitapide

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

              • lornoxicam

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

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

              • losartan

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

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

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor, diclofenac. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

              • meclofenamate

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

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

              • mefenamic acid

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

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

              • melatonin

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

              • meloxicam

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

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

              • mesalamine

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

              • metaproterenol

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • metoprolol

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

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

              • midazolam intranasal

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

              • milnacipran

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

              • mipomersen

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

              • mistletoe

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

              • moexipril

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

              • moxisylyte

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

              • mycophenolate

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

              • nabumetone

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

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

              • nadolol

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

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

              • naproxen

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

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

              • nebivolol

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

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

              • nefazodone

                nefazodone, diclofenac. 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

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

              • nicardipine

                nicardipine will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • nitisinone

                nitisinone will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

              • norepinephrine

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

              • olmesartan

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

                diclofenac 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, diclofenac. 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

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

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

              • panax ginseng

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

              • parecoxib

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

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

              • paroxetine

                paroxetine, diclofenac. 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

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

              • pegaspargase

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

              • peginterferon alfa 2b

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

              • penbutolol

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

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

              • perindopril

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

              • phenoxybenzamine

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

              • phentolamine

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

              • phytoestrogens

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

              • pindolol

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

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

              • pirbuterol

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

              • piroxicam

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

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

              • pivmecillinam

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

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • potassium iodide

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

              • pralatrexate

                diclofenac 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

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

              • prazosin

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

              • prednisolone

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

              • prednisone

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

              • probenecid

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

              • propranolol

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

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

              • protamine

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

              • quinapril

                quinapril, diclofenac. 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, diclofenac. 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

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

              • reteplase

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

              • rivaroxaban

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

              • rivastigmine

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

              • rucaparib

                rucaparib will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C9 substrates, if clinically indicated.

              • sacubitril/valsartan

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

                sacubitril/valsartan, diclofenac. 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.

                diclofenac 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)

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

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

              • salmeterol

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

              • salsalate

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

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

              • saw palmetto

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

              • sertraline

                sertraline, diclofenac. 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

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

              • silodosin

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

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

                diclofenac, 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 diclofenac 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 diclofenac 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

                diclofenac, 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 diclofenac both increase serum potassium. Use Caution/Monitor.

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

              • spironolactone

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

              • succinylcholine

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

              • sulfadiazine

                sulfadiazine will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • sulfasalazine

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

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

              • sulindac

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

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

              • tafluprost

                tafluprost, diclofenac. 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).

              • tazemetostat

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

              • telmisartan

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

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

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

              • tenecteplase

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

              • tenofovir DF

                tenofovir DF, diclofenac. 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

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

              • terbutaline

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

              • teriflunomide

                teriflunomide increases levels of diclofenac by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

              • ticagrelor

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

              • ticarcillin

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

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

              • timolol

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

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

              • tinidazole

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

              • tolazamide

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

              • tolbutamide

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

                tolbutamide will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • tolfenamic acid

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

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

              • tolmetin

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

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

              • tolvaptan

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

              • torsemide

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

              • trandolapril

                trandolapril, diclofenac. 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, diclofenac. 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, diclofenac. 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

                diclofenac, 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 diclofenac both increase serum potassium. Modify Therapy/Monitor Closely.

              • valsartan

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

                diclofenac 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, diclofenac. 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, diclofenac. 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, diclofenac. 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

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

              • voriconazole

                voriconazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Do not exceed diclofenac dose of 50 mg BID

              • vortioxetine

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

              • warfarin

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

              • zanubrutinib

                diclofenac, 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

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

              Minor (100)

              • aceclofenac

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

              • acemetacin

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

              • acyclovir

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

              • alendronate

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

              • amikacin

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

              • aminohippurate sodium

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

              • amiodarone

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

              • amobarbital

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

              • anamu

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

              • aspirin

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

              • aspirin rectal

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

              • balsalazide

                diclofenac 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 diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • bosentan

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

              • butabarbital

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

              • butalbital

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

              • carbamazepine

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

              • cefadroxil

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

              • cefamandole

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

              • cefpirome

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

              • celecoxib

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

              • cephalexin

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

              • cimetidine

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

              • colestipol

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

              • creatine

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

              • cyclopenthiazide

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

              • danshen

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

              • devil's claw

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

              • diclofenac topical

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

              • diflunisal

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

              • disulfiram

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

              • eplerenone

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

              • etodolac

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

              • etravirine

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

              • felbamate

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

              • fenbufen

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

              • fenoprofen

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

              • feverfew

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

              • flurbiprofen

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

              • furosemide

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

              • ganciclovir

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

              • gentamicin

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

              • hydrochlorothiazide

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

              • ibuprofen

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

              • imidapril

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

              • indapamide

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

              • indomethacin

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

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • leflunomide

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

              • lornoxicam

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

              • meclofenamate

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

              • mefenamic acid

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

              • meloxicam

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

              • mesalamine

                diclofenac 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 diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              • metolazone

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

              • metronidazole

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

              • miconazole vaginal

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

              • nabumetone

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

              • naproxen

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

              • nateglinide

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

              • neomycin PO

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

              • nilotinib

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

              • noni juice

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

              • ofloxacin

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

              • oxaprozin

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

              • parecoxib

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

              • paromomycin

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

              • pentobarbital

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

              • phenobarbital

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

              • piroxicam

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

              • primidone

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

              • rifampin

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

              • rifapentine

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

              • rose hips

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

              • ruxolitinib

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

              • salicylates (non-asa)

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

              • salsalate

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

              • secobarbital

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

              • streptomycin

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

              • sulfamethoxazole

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

              • sulfasalazine

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

              • sulindac

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

              • ticlopidine

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

              • tobramycin

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

              • tolfenamic acid

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

              • tolmetin

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

              • triamterene

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

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

              • valganciclovir

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

              • valproic acid

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

              • vancomycin

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

              • willow bark

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

              • zafirlukast

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

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              Adverse Effects

              >10%

              Rash including erythematous, rash macular and maculo-papular (18%)

              Pyrexia (15%)

              Urticaria (13%)

              Flushing (13%)

              1-10%

              Hypertension (10%)

              Hyperhydrosis (8%)

              Decreased oxygen saturation (8%)

              Cough (8%)

              Tachypnea (8%)

              Tachycardia (8%)

              Urticaria (8%)

              Anaphylaxis (7%

              Chest discomfort (7%)

              Muscle twitching (7%)

              Erythema (5%)

              Vomiting (5%)

              Rigors (5%)

              Pallor (5%)

              Cyanosis (5%)

              Agitation (5%)

              Tremor (5%)

              Myalgia (5%)

              Flushing (5%)

              Peripheral edema (3%)

              Pruritus (3%)

              Rash, papular (3%)

              Throat tightness (3%)

              <1%

              Fatigue

              Malaise

              Chills

              Edema

              Atrial fibrillation

              Congestive heart failure

              Myocardial infarction

              Phlebitis

              Vasculitis

              Syncope

              Dysphagia

              Enteritis

              Peptic ulcer

              Vaginitis

              Breast pain

              Dysmenorrhea

              Uterine cramping

              Ulcerative stomatitis

              Impotence

              Perineal pain

              Glycosuria

              Alopecia

              Postmarketing reports

              Increased alanine aminotransferase

              Increased alkaline phosphatase

              Increased aspartate aminotransferase

              Increased BUN

              Dehydration

              Glycosuria

              Gout

              Hypercholesterolemia

              Hyperglycemia

              Hyperuricemia

              Hypoglycemia

              Hyponatremia

              Periorbital edema porphyria

              Weight changes

              Fluid retention

              Body as a whole: Death, fever, infection, sepsis

              Cardiovascular system: Arrhythmia, hypotension, increased creatinine phosphokinase, increased lactate dehydrogenase, palpitations, premature ventricular contractions, syncope

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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

              Women with childbearing potential

              • Advise patient or abortificient property and warn not to give to others; not for women of childbearing potential unless patient requires nonsteroidal anti-inflammatory drug (NSAID) therapy and is at high risk of developing gastric or duodenal ulceration or complications from gastric or duodenal ulcers associated with NSAID use
              • Administration to women who are pregnant can cause abortion, premature birth, birth defects, or uttering rupture
              • Uterine rupture reported when misoprostol was administered in pregnant women to induce labor or abortion
              • Risk of uttering rupture increases with advancing gestational ages and with prior uttering surgery, including cesarean delivery; drug should not be administered to women who are pregnant
              • Prescribe to patients of childbearing potential only if the following conditions are met:
              • Has had a negative serum pregnancy test within 2 wk prior to beginning therapy
              • Is capable of complying with effective contraceptive measures
              • Has received both oral and written warnings of hazards of misoprostol, the risk of possible contraception failure, and danger to other women of childbearing potential should the drug be taken by mistake
              • Will begin diclofenac only on second or third day of the next normal menstrual period

              Contraindications

              Hypersensitivity drugs or related products

              Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; active gastrointestinal bleeding

              Patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

              Cautions

              Women of childbearing potential (see mfr's package insert for restrictions)

              Avoid pregnancy during & for at least 1 month after treatment

              May cause blurred vision, drowsiness, dizziness

              Transaminase elevation observed with chronic use

              Hypokalemia may occur when administered with drugs capable of inducing hyperkalemia; risk may increase in diabetics, renal disease, the elderly

              NSAIDs reported to cause serious skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome

              May increase risk of aseptic meningitis especially in patients with mixed connective tissue disorders and systemic lupus erythematous

              Severe bronchospasm may occur in patients with asthma

              Use caution in hepatic impairment, porphyria (avoid if possible), hypertension, renal impairment

              Avoid use of diclofenac/misoprostol with concomitant NSAIDs including COX inhibitors

              Use lowest effective dose in patients with known cardiovascular (CV) disease or risk factors for CV

              Concurrent use of aspirin with NSAIDs in mitigating CV thrombotic events not shown conclusively; increased risk of serious GI adverse reactions likely

              Use caution in patients with hypertension; monitor blood pressure closely during initiation of NSAID treatment and throughout the course of therapy

              Fluid retention and edema may occur with therapy; use with caution in patients with heart failure

              Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of stomach, small intestine, or large intestine, which can be fatal may occur

              Renal papillary necrosis and other renal injury reported with NSAID long-term therapy

              Toxic epidermal necrolysis, reported with NSAID use, especially within first month of therapy; discontinue use at first appearance of skin rash

              Use of NSAIDs may diminish ability to diagnose conditions associated with pain or inflammation

              Anemia reported with NSAID use; monitor

              Use caution in patients with coagulation disorders or receiving anticoagulants; NSAIDs inhibit platelet aggregation

              Not for administration to patients with aspirin-sensitive asthma; use caution in patients with preexisting asthma

              NSAIDs may diminish antihypertensive effect of ACE-inhibitors

              Not recommended in patients with advanced renal disease

              Drug-induced hepatotoxicity reported in first month, and may occur within 1-6 months, but can occur at any time during therapy

              GI bleeding

              • Serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of stomach, small intestine, or large intestine, which can be fatal may occur
              • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors
              • Other factors that increase risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet drugs (such as aspirin), anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status; most postmarketing reports of fatal GI events occurred in elderly or debilitated patients; additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding

              Hepatotoxicity

              • Meaningful elevations (ie, more than 3 times the ULN) of aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) reported
              • Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a complete blood count (CBC) and a chemistry profile periodically

              Drug reaction with eosinophilia and systemic symptoms (DRESS)

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

              Pregnancy

              Drug combination is contraindicated in pregnant women; there are no adequate and well-controlled studies in pregnant women; however, there is information available about the active drug components diclofenac sodium and misoprostol

              Administration of misoprostol to pregnant women can cause abortion, premature birth, birth defects or uterine rupture; congenital anomalies sometimes associated with fetal death have been reported subsequent to unsuccessful use of misoprostol as an abortifacient, but the drug’s teratogenic mechanism has not been demonstrated

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

              There are clinical considerations when misoprostol and diclofenac are used in pregnant women In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when the combination of diclofenac sodium and misoprostol was administered during organogenesis at doses less than the maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure

              Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization

              In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-and post-implantation loss; if a woman becomes pregnant while taking drug combination, discontinue drug and advise the woman of the potential risks to her and to a fetus

              Maternal adverse reactions

              • Misoprostol may produce uterine contractions, uterine bleeding, and expulsion of the products of conception; misoprostol has been used to ripen the cervix, to induce labor, and to treat postpartum hemorrhage, outside of its approved indication
              • A major adverse effect of these uses is hyperstimulation of the uterus; uterine rupture, amniotic fluid embolism, severe bleeding, shock, and maternal death have been reported when misoprostol was administered to pregnant women to induce labor to induce abortion beyond the eighth weeks of pregnancy
              • Higher doses of misoprostol, including the 100 mcg tablet, may increase the risk of complications from uterine hyperstimulation; the drug combination, which contains 200 mcg of misoprostol, is likely to have a greater risk of uterine hyperstimulation than the 100 mcg tablet of misoprostol
              • Abortions caused by misoprostol may be incomplete; cases of amniotic fluid embolism, which resulted in maternal and fetal death, have been reported with use of misoprostol during pregnancy
              • Severe vaginal bleeding, retained placenta, shock, and pelvic pain have also been reported; these women were administered misoprostol vaginally and/or orally over a range of doses; if a woman is or becomes pregnant while taking this drug, the drug should be discontinued and the patient apprised of the potential hazard to the fetus
              • Drug combination is contraindicated in pregnant women

              Fetal toxicity

              • Misoprostol may endanger pregnancy (may cause abortion) and thereby cause harm to the fetus when administered to a pregnant woman; use of misoprostol for the induction of labor in the third trimester was associated with uterine hyperstimulation with resulting changes in the fetal heart rate (fetal bradycardia) and fetal death
              • NSAIDs can cause premature closure of the fetal ductus arteriosus at about 30 weeks gestation and later in pregnancy and at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment
              • If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue treatment and follow up according to clinical practice

              Labor or delivery

              • There are no studies on the effects of drug combination or diclofenac during labor or delivery; in animal studies, NSAIDS, including diclofenac, are known to inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth;
              • In humans, some case reports and studies have associated misoprostol with risk of stillbirth, uterine hyperstimulation, perineal tear, amniotic fluid embolism, severe bleeding, shock, uterine rupture and death
              • The risk of uterine rupture associated with misoprostol use in pregnancy may occur at any gestational age, and increases with advancing gestational ages and with prior uterine surgery, including cesarean delivery; grand multiparity also appears to be a risk factor for uterine rupture

              Infertility

              • Based on mechanism of action, NSAIDs, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women
              • Animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation; small studies in women have also shown a reversible delay in ovulation in women treated with NSAIDs; consider withdrawal of NSAIDs, in women who have difficulties conceiving or who are undergoing investigation of infertility

              Animal data

              • In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when drug combination was administered during organogenesis at doses less than maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure
              • Based on animal data, prostaglandins have been shown to have important role in endometrial vascular permeability, blastocyst implantation, and decidualization; in animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-and post-implantation loss; if a woman becomes pregnant while receiving therapy, discontinue drug and advise woman of potential risks to her and to a fetus
              • In animal studies, NSAIDs are known to inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth

              Lactation

              No lactation studies conducted; however, limited published literature reports that diclofenac and active metabolite of misoprostol are present in breast milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

              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

              Diclofenac: Inhibits cyclooxygenase-1 (COX-1) & -2 (COX-2), thereby inhibiting prostaglandin synthesis; has anti-inflammatory, antipyresis, and analgesic properties

              Misoprostol: Replaces protective prostaglandins consumed by prostaglandin-inhibiting therapies (NSAID-induced ulcers)

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              Formulary

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              Tier Description
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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.