diclofenac/misoprostol (Rx)

Brand and Other Names:Arthrotec

Dosing & Uses

AdultPediatric

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

and diclofenac/misoprostol

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            Contraindicated (1)

            • fezolinetant

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

            Serious - Use Alternative (21)

            • 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 (269)

            • 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.

            • atogepant

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

            • 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.

            • 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.

            • 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.

            • isavuconazonium sulfate

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

            • 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.

            • levoketoconazole

              levoketoconazole 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

            • 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.

            • sparsentan

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

              sparsentan will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

            • 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

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

            • 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 (101)

            • 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.

            • ruxolitinib topical

              diclofenac will increase the level or effect of ruxolitinib topical 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 and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events

            Women with childbearing potential

            • Patient should be advised to use effective contraception during treatment
            • 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 uterine 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

            Pregnancy

            Cautions

            Caution in women of childbearing potential (see mfr's package insert for restrictions)

            NSAIDs increase risk of premature closure of the fetal ductus arteriosus at about 30 weeks of gestation and later

            Avoid pregnancy during & for at least 1 month after treatment

            Avoid use of this drug in patients with a recent MI unless benefits are expected to outweigh risk of recurrent CV thrombotic events; if this drug is used in patients with recent MI, monitor patients for signs of cardiac ischemia

            May cause blurred vision, drowsiness, dizziness

            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), or hypertension

            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

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

            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

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

            Therapy has been associated with anaphylactic reactions in patients with and without known hypersensitivity to the individual components of diclofenac sodium and misoprostol and in patients with aspirin-sensitive asthma

            NSAIDs can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal; these serious events may occur without warning; inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of this drug at the first appearance of skin rash or any other sign of hypersensitivity; this medication is contraindicated in patients with previous serious skin reactions to NSAIDs

            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

            Heart failure

            • Fluid retention and edema may occur with therapy; use with caution in patients with heart failure
            • In patients with heart failure, NSAID use have increased risk of MI, hospitalization for heart failure, and death; treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs])
            • Avoid use in patients with severe heart failure unless the benefits are expected to outweigh risk of worsening heart failure; if this drug is used in patients with severe heart failure, monitor patients for signs of worsening heart failure

            Hypertension

            • Use caution in patients with hypertension
            • NSAIDs, can lead to new onset of hypertension or worsening of pre-existing hypertension, either of which may contribute to increased incidence of CV events
            • Patients taking angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs
            • Monitor blood pressure (BP) during initiation of NSAID treatment and throughout course of therapy

            Cardiovascular thrombotic events

            • Patients with known CV disease or risk factors may have higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate; some observational studies have found that the increased risk of serious CV thrombotic events may begin as early as first weeks of treatment; increase in CV thrombotic risk has been observed most consistently at higher doses
            • To minimize potential risk for adverse CV event in NSAID-treated patients, use lowest effective dose for shortest duration possible; physicians and patients should remain alert for development of such events, throughout entire treatment course, even in absence of previous CV symptoms; patients should be informed about symptoms of serious CV events and the steps to take if they occur

            Exacerbation of asthma-related aspirin sensitivity

            • A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs
            • Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, this therapy is contraindicated in patients with this form of aspirin sensitivity
            • When this medication is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma

            Hematologic toxicity

            • Anemia has occurred in NSAID-treated patients; this may be due to occult or gross bloodloss, fluid retention, or an incompletely described effect on erythropoiesis; if a patient treated with this drug has any signs or symptoms of anemia, monitor hemoglobin or hematocrit
            • NSAIDs may increase the risk of bleeding events; co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet drugs (eg, aspirin), and SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase this risk; monitor these patients for signs of bleeding

            Geriatric use

            • Geriatric patients (those 65 years of age and older), compared to younger adult patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions; the risk of diclofenac-associated adverse reactions may be greater in geriatric patients with renal impairment or those taking concomitant ACE inhibitors or ARBs
            • Avoid use in geriatric patients with cardiovascular and/or renal risk factors; if use cannot be avoided, use lowest recommended dosage for shortest duration and monitor for cardiac and renal adverse reactions
            • Monitor renal function in geriatric patients during treatment, especially in patients with concomitant use of ACE inhibitors or ARBs
            • No clinically meaningful differences in the pharmacokinetics of diclofenac and misoprostol were observed in geriatric patients compared to younger adult patients

            Renal toxicity and hyperkalemia

            • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury; renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion
            • In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation
            • Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly; discontinuation of NSAID therapy is usually followed by recovery to pretreatment state
            • No information available from controlled clinical studies regarding use of this drug in patients with advanced renal disease; the renal effects of this medication may hasten the progression of renal dysfunction in patients with pre-existing renal disease
            • Correct volume status in dehydrated or hypovolemic patients prior to initiating therapy; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of this drug
            • Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function; if this drug is used in patients with advanced renal disease, monitor patients for signs of worsening renal function
            • Increases in serum potassium concentration, including hyperkalemia, reported, with use of NSAIDs, even in some patients without renal impairment; in patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state
            • Avoid use of this medication in patients with advanced renal disease; if use cannot be avoided in patients with advanced renal disease, use lowest dosage for shortest duration, monitor patient’s renal function, and monitor for clinical signs of worsening renal function

            Oligohydramnios/neonatal renal impairment

            • Use of NSAIDs, including diclofenac, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment; these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation
            • Oligohydramnios is often, but not always, reversible with treatment discontinuation; complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation; in some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required

            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
            • Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs may occur in 1% patients treated for 3-6 months, and in about 2-4% of patients treated for one year; however, even short-term NSAID therapy is not without risk
            • Strategies to minimize GI risks in NSAID-treated patients
              • Use lowest effective dosage for shortest possible duration
              • Avoid administration of more than one NSAID at a time
              • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
              • If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue therapy until a serious GI adverse event is ruled out
              • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

            Hepatotoxicity

            • Meaningful elevations (ie, more than 3 times the ULN) of alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT], aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) reported; these increases were generally transient, and enzyme levels returned to within the normal range upon discontinuation of therapy misoprostol component does not appear to exacerbate hepatic effects caused by diclofenac sodium component
            • Elevations of ALT or AST reported in patients receiving diclofenac when compared to other NSAIDs; elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis
            • Almost all meaningful elevations in transaminases have been detected before patients became symptomatic; in postmarketing reports, cases of drug-induced hepatotoxicity have been reported in first month, and in some cases, first 2 months of therapy, but can occur at any time during treatment with diclofenac
            • Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure; some of these reported cases resulted in fatalities or liver transplantation
            • Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms
            • Optimum times for making first and subsequent transaminase measurements are not known; based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4-8 weeks after initiating treatment with diclofenac; however, severe hepatic reactions can occur at any time during treatment with diclofenac
            • If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc), therapy should be discontinued immediately
            • To minimize potential risk for adverse liver related event in patients treated with this drug, the lowest effective dose should be used for shortest duration possible
            • Exercise caution when prescribing this drug with concomitant drugs that are known to be potentially hepatotoxic (eg, antibiotics, anti-epileptics)

            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

            Not recommended in women of childbearing potential; if prescribed, patient must be advised of abortifacient property and warned not to give drug to others; advise females to inform their healthcare provider of a known or suspected 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 (misoprostol is not approved for this use)
            • 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.