diclofenac (Rx)

Brand and Other Names:Cataflam, Voltaren-XR, more...Dyloject, Cambia, Zipsor, Zorvolex
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

diclofenac potassium

packet

  • 50mg/single-dose packet (generic, Cambia)
  • Delivers 50-mg dose when mixed in water

tablet

  • 50mg (generic)

capsule

  • 25mg (Zipsor)

diclofenac sodium

tablet, delayed release

  • 25mg (generic)
  • 50mg (generic)
  • 75mg (generic)

tablet, extended-release

  • 100mg (generic)

capsule

  • 18mg (Zorvolex)
  • 35mg (Zorvolex)

Rheumatoid Arthritis

Diclofenac potassium: 50 mg PO q8-12hr

Diclofenac sodium: 50 mg PO q8hr or 75 mg PO q12hr

Extended release: 100 mg PO once daily; may be increased to 100 mg PO q12hr

Osteoarthritis

Diclofenac potassium: 50 mg PO q8-12hr

Diclofenac sodium: 50 mg PO q8hr or 75 mg PO q12hr

Extended release: 100 mg PO once daily; may be increased to 100 mg PO q12hr

Zorvolex: 35 mg PO TID

Ankylosing Spondylitis

Diclofenac sodium: 25 mg PO 4 or 5 times daily

Diclofenac potassium: 50 mg PO q12hr

Dysmenorrhea

Immediate-release: 100 mg PO once, then 50 mg PO q8hr PRN

Acute Pain

Indicated for treatment of mild to moderate acute pain in adults

Immediate-release tablets: 100 mg PO once, then 50 mg PO q8hr PRN

Extended-release tablets

  • Zipsor: 25 mg PO QID PRN
  • Zorvolex: 18 mg or 35 mg PO TID

Use the lowest effective dose for the shortest duration consistent with individual patient treatment goal

Acute Migraine

Indicated for acute treatment of migraine attacks with or without aura

Cambia: 50 mg (1 packet) in 30-60 mL of water, mixed well and drunk immediately

Not for prophylaxis

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

Dosage Modifications

Renal impairment

  • Patients with renal impairment had AUC values and elimination rates that were comparable to healthy patients

Hepatic impairment

  • Hepatic metabolism accounts for almost 100% of diclofenac elimination
  • There is insufficient information available to support dosing recommendations
  • Start with the lowest dose; if efficacy is not achieved, consider using an alternant

Dosing Considerations

Limitations of use

  • Not indicated for the prophylactic therapy of migraine
  • Safety and effectiveness not established for cluster headache, which is present in an older, predominantly male population

Dosage Forms & Strengths

diclofenac potassium

capsule

  • 25mg (Zipsor)

Acute Pain

Zipsor only

Indicated for relief of mild-to-moderate pain in adult and pediatric patients aged ≥12 years

<12 years: Safety and efficacy not established

≥12 years: 25 mg PO QID PRN

Dosage Modifications

Renal impairment

  • Patients with renal impairment had AUC values and elimination rates that were comparable to healthy patients

Hepatic impairment

  • Hepatic metabolism accounts for almost 100% of diclofenac elimination
  • There is insufficient information available to support dosing recommendations
  • Start with the lowest dose; if efficacy is not achieved, consider using an alternant

Dosing Considerations

Limitations of use

  • Not indicated for the prophylactic therapy of migraine
  • Safety and effectiveness not established for cluster headache, which is present in an older, predominantly male population

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Interactions

Interaction Checker

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              Serious - Use Alternative (23)

              • 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.

              • 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.

              • 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.

              • 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.

              • perindopril

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

              • pexidartinib

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

              • pirfenidone

                diclofenac will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration of pirfenidone and moderate CYP1A2 inhibitors result in moderately increased exposure to pirfenidone; if unable to avoid, decrease dose of moderate CYP1A2 inhibitor

              • quinapril

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

              • ramipril

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

              • tacrolimus

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

              • trandolapril

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

              Monitor Closely (267)

              • acebutolol

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

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

              • aceclofenac

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

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

              • acemetacin

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

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

              • agrimony

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

              • albuterol

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

              • alfalfa

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

              • alfuzosin

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

              • aliskiren

                diclofenac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              • alpelisib

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

              • alteplase

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

              • American ginseng

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

              • amiloride

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

              • antithrombin alfa

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

              • antithrombin III

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

              • apalutamide

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

              • arformoterol

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

              • argatroban

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

              • artesunate

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

              • asenapine

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

              • aspirin

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

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

              • aspirin rectal

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

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

              • aspirin/citric acid/sodium bicarbonate

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

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

              • atazanavir

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

              • atenolol

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

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

              • avapritinib

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

              • axitinib

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

              • azficel-T

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

              • azilsartan

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

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

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

              • bemiparin

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

              • benazepril

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

              • bendroflumethiazide

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

              • betaxolol

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

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

              • betrixaban

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

              • bimatoprost

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

              • bisoprolol

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

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

              • bivalirudin

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

              • budesonide

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

              • bumetanide

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

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

              • candesartan

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

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

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

              • cannabidiol

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

              • capecitabine

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

              • captopril

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

              • carbenoxolone

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

              • carvedilol

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

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

              • celecoxib

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

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

              • celiprolol

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

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • cholestyramine

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

              • choline magnesium trisalicylate

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

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

              • cinnamon

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

              • ciprofloxacin

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

              • citalopram

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

              • clobetasone

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

              • clomipramine

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

              • clopidogrel

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

              • cordyceps

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

              • cortisone

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

              • cyclopenthiazide

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

              • cyclosporine

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

              • dabigatran

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

              • dalteparin

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

              • deferasirox

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

              • deferiprone

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

              • defibrotide

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

              • deflazacort

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

              • dexamethasone

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

              • diflunisal

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

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

              • digoxin

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

              • dobutamine

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

              • dong quai

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

              • dopexamine

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

              • doxazosin

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

              • drospirenone

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

              • duloxetine

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

              • edoxaban

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

              • efavirenz

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

              • eltrombopag

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

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

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

              • emtricitabine

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

              • enalapril

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

              • enoxaparin

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

              • ephedrine

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

              • epinephrine

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

              • epinephrine racemic

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

              • epoprostenol

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

              • eprosartan

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

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

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

              • escitalopram

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

              • esmolol

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

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

              • ethacrynic acid

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

              • etodolac

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

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

              • fenbufen

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

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

              • fennel

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

              • fenoprofen

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

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

              • feverfew

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

              • finerenone

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

              • fish oil triglycerides

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

              • flibanserin

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

              • flucloxacillin

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

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

              • fluconazole

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

              • fludrocortisone

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

              • fluorouracil

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

              • fluoxetine

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

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

              • flurbiprofen

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

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

              • fluvoxamine

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

              • fondaparinux

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

              • formoterol

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

              • forskolin

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

              • fosinopril

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

              • furosemide

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

              • garlic

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

              • gemfibrozil

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

              • gemifloxacin

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

              • gentamicin

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

              • ginger

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

              • ginkgo biloba

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

              • glimepiride

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

              • glipizide

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

              • glyburide

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

              • green tea

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

              • heparin

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

              • horse chestnut seed

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

              • hydralazine

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

              • hydrochlorothiazide

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

              • hydrocortisone

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

              • ibrutinib

                ibrutinib will increase the level or effect of diclofenac by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

              • ibuprofen

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

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

              • ibuprofen IV

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

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

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

              • imatinib

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

                imatinib, diclofenac. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

              • indapamide

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

              • indomethacin

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

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

              • irbesartan

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

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

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

              • isoproterenol

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

              • ivacaftor

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

              • ketoconazole

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

              • ketoprofen

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

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

              • ketorolac

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

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

              • ketorolac intranasal

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

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

              • labetalol

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

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

              • latanoprost

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

              • latanoprostene bunod ophthalmic

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

              • lemborexant

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

              • levalbuterol

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

              • levofloxacin

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

              • levomilnacipran

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

              • lisinopril

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

              • lithium

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

              • lomitapide

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

              • lornoxicam

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

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

              • losartan

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

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

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

              • lumacaftor/ivacaftor

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

              • meclofenamate

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

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

              • mefenamic acid

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

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

              • melatonin

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

              • meloxicam

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

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

              • mesalamine

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

              • metaproterenol

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

              • methyclothiazide

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

              • methylprednisolone

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

              • metolazone

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

              • metoprolol

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

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

              • midazolam intranasal

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

              • milnacipran

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

              • mipomersen

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

              • mistletoe

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

              • moexipril

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

              • moxifloxacin

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

              • moxisylyte

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

              • mycophenolate

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

              • nabumetone

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

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

              • nadolol

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

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

              • naproxen

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

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

              • nebivolol

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

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

              • nefazodone

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

              • nettle

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

              • nicardipine

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

              • nitisinone

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

              • norepinephrine

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

              • olmesartan

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

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

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

              • oxaprozin

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

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

              • panax ginseng

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

              • parecoxib

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

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

              • paroxetine

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

              • pau d'arco

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

              • pegaspargase

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

              • peginterferon alfa 2b

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

              • penbutolol

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

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

              • perindopril

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

              • phenindione

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

              • phenoxybenzamine

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

              • phentolamine

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

              • phytoestrogens

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

              • pindolol

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

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

              • pirbuterol

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

              • piroxicam

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

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

              • pivmecillinam

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

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

              • potassium acid phosphate

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

              • potassium chloride

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

              • potassium citrate

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

              • potassium iodide

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

              • pralatrexate

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

              • prasugrel

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

              • prazosin

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

              • prednisolone

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

              • prednisone

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

              • probenecid

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

              • propranolol

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

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

              • protamine

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

              • quinapril

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

              • ramipril

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

              • reishi

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

              • reteplase

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

              • rivaroxaban

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

              • rivastigmine

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

              • rucaparib

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

              • sacubitril/valsartan

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

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

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

              • salicylates (non-asa)

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

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

              • salmeterol

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

              • salsalate

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

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

              • saw palmetto

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

              • sertraline

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

              • Siberian ginseng

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

              • silodosin

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

              • sodium picosulfate/magnesium oxide/anhydrous citric acid

                diclofenac, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

              • sodium sulfate/?magnesium sulfate/potassium chloride

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

              • sodium sulfate/potassium sulfate/magnesium sulfate

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

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

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

              • sotalol

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

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

              • spironolactone

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

              • succinylcholine

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

              • sulfadiazine

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

              • sulfasalazine

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

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

              • sulindac

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

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

              • tafluprost

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

              • tazemetostat

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

              • telmisartan

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

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

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

              • temocillin

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

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

              • tenecteplase

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

              • tenofovir DF

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

              • terazosin

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

              • terbutaline

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

              • teriflunomide

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

              • ticagrelor

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

              • ticarcillin

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

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

              • timolol

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

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

              • tinidazole

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

              • tolazamide

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

              • tolbutamide

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

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

              • tolfenamic acid

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

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

              • tolmetin

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

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

              • tolvaptan

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

              • torsemide

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

              • trandolapril

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

              • travoprost ophthalmic

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

              • trazodone

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

              • triamcinolone acetonide injectable suspension

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

              • triamterene

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

              • valsartan

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

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

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

              • venlafaxine

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

              • voclosporin

                voclosporin, diclofenac. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

              • vorapaxar

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

              • voriconazole

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

              • vortioxetine

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

              • warfarin

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

              • zanubrutinib

                diclofenac, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

              • zotepine

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

              Minor (100)

              • aceclofenac

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

              • acemetacin

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

              • acyclovir

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

              • alendronate

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

              • amikacin

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

              • aminohippurate sodium

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

              • amiodarone

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

              • amobarbital

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

              • anamu

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

              • aspirin

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

              • aspirin rectal

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

              • aspirin/citric acid/sodium bicarbonate

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

              • balsalazide

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

              • bendroflumethiazide

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

              • bosentan

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

              • butabarbital

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

              • butalbital

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

              • carbamazepine

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

              • cefadroxil

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

              • cefamandole

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

              • cefpirome

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

              • celecoxib

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

              • cephalexin

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

              • chlorothiazide

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

              • chlorpropamide

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

              • chlorthalidone

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

              • choline magnesium trisalicylate

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

              • cimetidine

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

              • colestipol

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

              • creatine

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

              • cyclopenthiazide

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

              • danshen

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

              • devil's claw

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

              • diclofenac topical

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

              • diflunisal

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

              • disulfiram

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

              • eplerenone

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

              • etodolac

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

              • etravirine

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

              • felbamate

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

              • fenbufen

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

              • fenoprofen

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

              • feverfew

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

              • flurbiprofen

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

              • furosemide

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

              • ganciclovir

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

              • gentamicin

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

              • hydrochlorothiazide

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

              • ibuprofen

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

              • imidapril

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

              • indapamide

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

              • indomethacin

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

              • ketoprofen

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

              • ketorolac

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

              • ketorolac intranasal

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

              • leflunomide

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

              • lornoxicam

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

              • meclofenamate

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

              • mefenamic acid

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

              • meloxicam

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

              • mesalamine

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

              • methyclothiazide

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

              • metolazone

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

              • metronidazole

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

              • miconazole vaginal

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

              • nabumetone

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

              • naproxen

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

              • nateglinide

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

              • neomycin PO

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

              • nilotinib

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

              • noni juice

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

              • ofloxacin

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

              • oxaprozin

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

              • parecoxib

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

              • paromomycin

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

              • pentobarbital

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

              • phenobarbital

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

              • piroxicam

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

              • primidone

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

              • rifampin

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

              • rifapentine

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

              • rose hips

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

              • ruxolitinib

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

              • salicylates (non-asa)

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

              • salsalate

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

              • secobarbital

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

              • streptomycin

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

              • sulfamethoxazole

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

              • sulfasalazine

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

              • sulindac

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

              • ticlopidine

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

              • tobramycin

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

              • tolfenamic acid

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

              • tolmetin

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

              • triamterene

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

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

              • valganciclovir

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

              • valproic acid

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

              • vancomycin

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

              • willow bark

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

              • zafirlukast

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

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              Adverse Effects

              >10%

              Zorvolex

              • Edema (33%)
              • Nausea (27%)
              • Headache (13%)

              Zipsor

              • Nausea (16.5%)
              • Headache (12.5%)

              1-10%

              Cambia

              • Nausea (3%)
              • Dizziness (1%)

              Diclofenac potassium tablets

              • Abdominal pain
              • Constipation
              • Diarrhea
              • Dyspepsia
              • Flatulence
              • Gross bleeding/perforation
              • Heartburn
              • Nausea
              • GI ulcers (gastric/duodenal)
              • Vomiting
              • Abnormal renal function
              • Anemia
              • Dizziness
              • Edema
              • Elevated liver enzymes
              • Headaches
              • Increased bleeding time
              • Pruritus
              • Rashes
              • Tinnitus

              Zorvolex

              • Dizziness (10%)
              • Vomiting (9%)
              • Constipation (8%)
              • Pruritus (7%)
              • Flatulence (3%)
              • Pain in extremity (3%)
              • Dyspepsia (2%)

              Zipsor

              • Abdominal pain (7%)
              • Vomiting (5.8%)
              • Dizziness (3.5%)
              • Constipation (3.2%)
              • Somnolence (2.6%)
              • Diarrhea (2.3%)
              • Pruritus (1.4%)
              • Dyspepsia (1.2%)
              • Sweating increased (1.2%)

              <1%

              Cambia

              • Urticaria (0.2%)
              • Flushing (0.2%)

              Postmarketing Reports

              Body as a whole: Fever, infection, sepsis, anaphylactic reactions, appetite changes, death

              Cardiovascular system: Congestive heart failure (CHF), hypertension, tachycardia, syncope, arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

              Digestive system: Dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice, colitis, eructation, liver failure, pancreatitis

              Hemic and lymphatic system: Ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia, agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

              Metabolic and nutritional: Weight changes, hyperglycemia

              Nervous system: Anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo, convulsions, coma, hallucinations, meningitis

              Respiratory system: Asthma, dyspnea, respiratory depression, pneumonia

              Skin and appendages: Alopecia, photosensitivity, sweating increased, angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Steven Johnson syndrome, urticaria

              Special senses: Blurred vision, conjunctivitis, hearing impairment

              Urogenital system: Cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

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              Warnings

              Black Box Warnings

              Cardiovascular risk

              • Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
              • Risk may increase with duration of use
              • Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
              • Use of COX-2 selective NSAID for pain treatment in the first 10­14 days following CABG surgery increased incidence of MI and stroke; use of NSAIDS is contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery

              Gastrointestinal risk

              • NSAIDs can increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
              • May occur at any time during use and without warning symptoms
              • Patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events

              Contraindications

              Hypersensitivity (eg, anaphylaxis, serious skin reactions) to diclofenac or any components of the product

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

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

              Zipsor capsules are contraindicated in patients with history of hypersensitivity to bovine protein

              Cautions

              Use caution in patients with bronchospasm, cardiac disease, CHF, hepatic porphyria, hypertension, fluid retention, severe renal impairment, smoking, systemic lupus erythematosus

              Platelet aggregation and adhesion may be decreased; may prolong bleeding time

              Use caution in blood dyscrasias or bone marrow depression; also with thrombocytopenia, agranulocytosis, and aplastic anemia

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

              Increase risk of hyperkalemia may occur, especially in renal disease, diabetics, the elderly, and concomitant use of agents that may induce hyperkalemia; monitor potassium closely

              May cause dizziness blurred vision and neurologic effects that may impair physical and mental abilities

              Risk of serious skin reactions, including Stevens Johnson syndrome and necrotizing enterocolitis

              Persistent urinary symptoms, including bladder pain and dysuria, hematuria or cystitis may occur after initiating therapy; discontinue therapy with symptom onset and evaluate cause

              May increase risk of aseptic meningitis (rare), especially in patients with systemic lupus erythrmatosus, and mixed connective tissue disorders

              Use caution if patient dehydrated before initiating therapy; rehydrate patient before initiating therapy and monitor renal function closely

              Avoid use of NSAIDs in pregnant women at about ≥30 weeks gestation

              Use of NSAIDs at about ≥20 weeks gestation in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment

              Overuse of acute migraine drugs (eg, ergotamine, triptans, opioids, nonsteroidal anti-inflammatory drugs or combination of these drugs for ≥10 days per month) may lead to exacerbation of headache (medication overuse headache); may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks; detoxification of patients, including withdrawal of overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary

              Different formulations not bioequivalent even if milligram strength the same; do not interchange products

              Withhold for at least 4-6 half-lives prior to surgical or dental procedures

              Drug reaction with eosinophilia and systemic symptoms (DRESS)

              • Drug reaction reported; 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; disorder varies in 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
              • Heart failure risk H4
              • NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
              • NSAIDS should be avoided or withdrawn whenever possible

              Gastrointestinal bleeding, ulceration, perforation

              • Risk factors for GI bleeding, ulceration, and perforation
                • Prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs Other
                • Patients treated with NSAIDs include longer duration of NSAID therapy
                • Coadministration of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRI)
                • Smoking
                • Alcohol use
                • Older age
                • Poor general health status
                • Elderly or debilitated patients
                • Patients with advanced liver disease and/or coagulopathy
              • Strategies to minimize the GI risk in NSAID-treated patients
                • Use the lowest effective dosage for the shortest possible duration
                • Avoid using more than 1 NSAID at a time
                • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding
                • Consider alternants for high-risk patients, as well as those with active GI bleeding
                • Monitor 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, closely monitor for evidence of GI bleeding

              Hepatoxicity

              • Increase in transaminase levels reported within 2 months of therapy; may occur at any time
              • Monitor transaminase levels periodically beginning 4-8 weeks after initiation of therapy
              • Exercise caution when used with drugs that are known to be potentially hepatotoxic (eg, acetaminophen, certain antibiotics, antiepileptics)
              • Caution patients to avoid taking nonprescription acetaminophen-containing products while using diclofenac

              Hypertension

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

              Drug interaction overview

              • Drugs that interfere with hemostasis
                • Monitor for bleeding
                • Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. Use with anticoagulants have an increased risk of serious bleeding
                • Serotonin release by platelets plays an important role in hemostasis
                • Monitor for signs of bleeding in patients concomitantly using anticoagulants (eg, warfarin), antiplatelet agents (eg, aspirin), selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors
              • Salicylates
                • Not generally recommended
                • Diclofenac with other NSAIDs or salicylates (eg, diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy
                • ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers H5
                • Monitor for signs of worsening renal function in high-risk patients (eg, elderly patients, volume depleted, renal impaired patients)
                • NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers
              • Diuretics
                • Monitor patients to assure diuretic efficacy including antihypertensive effects
                • NSAIDs can reduce natriuretic effect of loop and thiazide diuretics
              • Digoxin
                • Monitor serum digoxin level
                • Diclofenac can increase serum concentration and prolong half-life of digoxin
              • Pemetrexed
                • Monitor for myelosuppression, renal, and GI toxicity during coadministration of NSAIDS with pemetrexed in renally impaired patients (CrCl 45-79 mL/min)
                • Avoid NSAIDs with short elimination half-lives (eg, diclofenac, indomethacin) for a period of 2 days before, the day of, and 2 days following administration of pemetrexed
                • Interrupt dosing of NSAIDs with longer half-lives (eg, meloxicam, nabumetone) for at least 5 days before, during, and 2 days following pemetrexed administration
                • Diclofenac may increase the risk of pemetrexed­-associated myelosuppression, renal, and GI toxicity
              • CYP2C9 inhibitors
                • Consider increasing duration of diclofenac doses for subsequent migraine attacks
                • CYP2C9 inhibitors may affect the pharmacokinetics of diclofenac
              • Cyclosporine
                • Monitor for signs of worsening renal function
                • Diclofenac may increase cyclosporine nephrotoxicity
              • Methotrexate
                • Monitor for methotrexate toxicity
                • NSAIDS may increase the risk for methotrexate toxicity (eg, neutropenia, thrombocytopenia, renal dysfunction)
              • Lithium
                • Monitor for signs of lithium toxicity
                • NSAIDs elevated plasma lithium levels and reduced renal lithium clearance
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              Pregnancy & Lactation

              Pregnancy

              There are no studies on effects of drug during labor or delivery

              Premature closure of fetal ductus arteriosus

              • Use of NSAIDs can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
              • Limit dose and duration of use to ~20-30 weeks of gestation; avoid use at about 30 weeks of gestation and later in pregnancy
              • Use of NSAIDs at ≥30 weeks gestation in pregnancy increases risk of premature closure of fetal ductus arteriosus

              Oligohydramnios/neonatal renal impairment

              • Use of NSAIDs at about ≥20 weeks gestation in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment
              • Data from observational studies regarding other potential embryofetal risks of NSAID use in women in first or second trimesters of pregnancy are inconclusive
              • Avoid use of NSAIDs in women at about 30 weeks gestation in pregnancy, because NSAIDs can cause premature closure of fetal ductus arteriosus
              • If an NSAID is necessary at about ≥20 weeks gestation in pregnancy, limit use to lowest dose and shortest duration possible; if treatment extends beyond 48 hr, consider monitoring with ultrasound for oligohydramnios
              • If oligohydramnios occurs, discontinue therapy, and follow up according to clinical practice

              Animal data

              • NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth

              Infertility

              • Females
                • Based on mechanism of action, use of prostaglandin-mediated NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility
                • Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
                • Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing investigation of infertility

              Animal data

              • In published studies, administration of clinically relevant doses of diclofenac to pregnant rats produced adverse effects on brain, kidney, and testicular development
              • Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization
              • Administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre-and post-implantation loss; prostaglandins also have been shown to have an important role in fetal kidney development
              • Prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses

              Lactation

              Data from published literature reports with oral preparations of diclofenac indicate the presence of diclofenac in small amounts human milk

              There are no data on effects on breastfed infant, or on milk production

              Pregnancy Categories

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

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

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

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

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

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

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

              May also inhibit neutrophil aggregation/activation, inhibit chemotaxis, decrease proinflammatory cytokine level, and alter lymphocyte activity

              Absorption

              Absolute bioavailability

              • Diclofenac potassium: 55%

              Peak plasma concentration

              • Cambia: ~0.25 hr
              • Zipsor: 1,087 ng/mL (adults); 699 ng/mL (aged 12-17 years)

              Peak plasma time

              • Diclofenac potassium: 1 hr
              • Zipsor: 0.47 hr (adults); 0.94 hr (aged 12-17 years)

              AUC

              • Zipsor: 597 ng⋅hr/mL(adults); 659 ng·hr/mL (aged 12-17 years)

              Effect of food

              • Capsules: 60% lower peak plasma concentration, 11% lower AUC, and 2.32 hr delayed peak plasma time under fed conditions; effectiveness when taken with food has not been studied
              • High-fat meal
                • Diclofenac potassium: No significant on extent of diclofenac absorption, but reduction in peak plasma levels of ~70% after high-fat meal

              Distribution

              Diclofenac diffuses into and out of the synovial fluid; unknown whether diffusion into the joint plays a role in the effectiveness of diclofenac

              Vd

              • Diclofenac potassium: 1.3 L/kg

              Protein bound

              • Diclofenac potassium: >99%

              Metabolism

              Metabolites: 4’- hydroxy-, 5-hydroxy-, 3’-hydroxy-, 4’,5-dihydroxy- and 3’-hydroxy-4’-methoxy diclofenac

              Formation of 4’- hydroxy- diclofenac is primarily mediated by CYP2C9

              Diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion

              Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism

              CYP3A4 is responsible for formation of minor metabolites, 5-hydroxy and 3’-hydroxy- diclofenac

              Elimination

              Half-life

              • Unchanged diclofenac: ~2 hr
              • Mean: 1.9 hr
              • Zipsor: 1.07 hr (adults); 1.81 (aged 12-17 years)

              Excretion

              • As unchanged diclofenac and metabolites
              • Urine (~65%); bile (~35%)
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              Administration

              Oral preparation

              Cambia

              • Empty the contents of 1 packet into a cup containing 1-2 ounces or 2-4 tablespoons (30-60 mL) of water, mix well and drink immediately
              • Do not use liquids other than water

              Oral Administration

              • Different formulations of diclofenac not necessarily bioequivalent even if milligram strength is the same
              • Zorvolex, Cataflam, and Cambia

                • May be taken with food to decrease GI distress
                • However, food may reduce effectiveness
                • Effectiveness when taken with food has not been studied

              Storage

              Diclofenac potassium immediate-release tablets: Store at 20-25ºC (68-77ºF); dispense in a tight container

              Zipsor: Store at 20-25ºC (68-77ºF); dispense in a tight container; protect from moisture

              Cambia: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

              Zorvolex

              • Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
              • Store in original container and keep bottle tightly closed to protect from moisture
              • Dispense in a tight container if package is subdivided
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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac ophthalmic (eye)
              -
              0.1 % drops
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              1 % gel
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              3 % gel
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              3 % gel
              diclofenac sodium topical
              -
              1 % gel
              diclofenac sodium topical
              -
              3 % gel
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              1 % gel
              diclofenac sodium topical
              -
              3 % gel
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              1 % gel
              diclofenac sodium topical
              -
              1 % gel
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              1.5 % drops
              diclofenac sodium topical
              -
              3 % gel
              Solaraze topical
              -
              3 % gel
              diclofenac oral
              -
              50 mg tablet
              diclofenac oral
              -
              50 mg tablet
              diclofenac oral
              -
              75 mg tablet
              diclofenac oral
              -
              100 mg tablet
              diclofenac oral
              -
              50 mg tablet
              diclofenac oral
              -
              100 mg tablet
              diclofenac oral
              -
              50 mg tablet
              diclofenac oral
              -
              25 mg tablet
              diclofenac oral
              -
              75 mg tablet
              diclofenac oral
              -
              75 mg tablet
              diclofenac oral
              -
              75 mg tablet
              diclofenac oral
              -
              100 mg tablet
              diclofenac oral
              -
              75 mg tablet
              diclofenac oral
              -
              100 mg tablet
              diclofenac oral
              -
              50 mg tablet
              diclofenac oral
              -
              25 mg tablet
              diclofenac oral
              -
              50 mg tablet
              Pennsaid topical
              -
              20 mg/gram /actuation(2 %) solution

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

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              Patient Education
              diclofenac oral

              DICLOFENAC SODIUM SUSTAINED-ACTION TABLET - ORAL

              (dye-KLOE-fen-ack SOE-dee-um)

              COMMON BRAND NAME(S): Voltaren-XR

              WARNING: Nonsteroidal anti-inflammatory drugs (including diclofenac) may rarely increase the risk for a heart attack or stroke. This effect can happen at any time while taking this drug but is more likely if you take it for a long time. The risk may be greater in older adults or if you have heart disease or increased risk for heart disease (for example, due to smoking, family history of heart disease, or conditions such as high blood pressure or diabetes). Do not take this drug right before or after heart bypass surgery (CABG).Also, this drug may rarely cause serious (rarely fatal) bleeding from the stomach or intestines. This effect can occur without warning symptoms at any time while taking this drug. Older adults may be at higher risk for this effect. (See also Precautions and Drug Interactions sections.)Stop taking diclofenac and get medical help right away if you notice any of the following rare but serious side effects: bloody or black/tarry stools, persistent stomach/abdominal pain, vomit that looks like coffee grounds, chest/jaw/left arm pain, shortness of breath, unusual sweating, weakness on one side of the body, sudden vision changes, trouble speaking.Talk with your doctor or pharmacist about the risks and benefits of treatment with this medication.

              USES: Diclofenac is used to relieve pain, swelling (inflammation), and joint stiffness caused by arthritis. Reducing these symptoms helps you do more of your normal daily activities. This medication is known as a nonsteroidal anti-inflammatory drug (NSAID). This long-acting medication is not intended to relieve sudden severe pain because it starts working slowly.If you are treating a chronic condition such as arthritis, ask your doctor about non-drug treatments and/or using other medications to treat your pain. See also Warning section.

              HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using diclofenac and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with a full glass of water (8 ounces / 240 milliliters) unless your doctor directs you otherwise, usually once daily. Do not lie down for at least 10 minutes after taking this drug. To prevent stomach upset, take this medication with food, milk, or an antacid.Do not crush or chew this medication. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.There are different brands and forms of this medication available. Because different brands deliver different amounts of medication, do not switch brands of diclofenac without your doctor's permission and directions.The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To minimize side effect risks (such as stomach bleeding), use this medication at the lowest effective dose for the shortest possible length of time. Do not increase your dose or take it more often than prescribed. Discuss the risks and benefits with your doctor or pharmacist.Take this medication regularly in order to get the most benefit from it. Remember to take it at the same time each day. It may take up to 2 weeks of regular use before the full benefits of this drug take effect.Tell your doctor if your condition worsens.

              SIDE EFFECTS: See also Warning section.Upset stomach, nausea, heartburn, diarrhea, constipation, gas, headache, drowsiness, and dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.Tell your doctor right away if any of these unlikely but serious side effects occur: hearing changes (such as ringing in the ears), mental/mood changes, difficult/painful swallowing, symptoms of heart failure (such as swelling ankles/feet, unusual tiredness, unusual/sudden weight gain).Get medical help right away if any of these rare but very serious side effects occur: signs of kidney problems (such as change in the amount of urine), unexplained stiff neck.This drug may rarely cause serious (possibly fatal) liver disease. Get medical help right away if you have any symptoms of liver damage, including: dark urine, persistent nausea/vomiting/loss of appetite, stomach/abdominal pain, yellowing eyes or skin.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: See also Warning section.Before taking diclofenac, tell your doctor or pharmacist if you are allergic to it; or to aspirin or other NSAIDs (such as ibuprofen, naproxen, celecoxib); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma (including a history of worsening breathing after taking aspirin or other NSAIDs), bleeding or clotting problems, growths in the nose (nasal polyps), heart disease (such as previous heart attack), high blood pressure, liver disease, stomach/intestinal/esophagus problems (such as bleeding, ulcers, recurring heartburn), stroke.Kidney problems can sometimes occur with the use of NSAID medications, including diclofenac. Problems are more likely to occur if you are dehydrated, have heart failure or kidney disease, are an older adult, or if you take certain medications (see also Drug Interactions section). Drink plenty of fluids as directed by your doctor to prevent dehydration and tell your doctor right away if you have a change in the amount of urine.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Talk to your doctor if you are using marijuana (cannabis).This medicine may cause stomach bleeding. Daily use of alcohol and tobacco, especially when combined with this medicine, may increase your risk for stomach bleeding. Limit alcohol and stop smoking. Consult your doctor or pharmacist for more information.This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.Older adults may be at greater risk for stomach/intestinal bleeding, kidney problems, heart attack, stroke, and worsening heart problems while using this drug.Before using this medication, women of childbearing age should talk with their doctor(s) about the benefits and risks. Tell your doctor if you are pregnant or if you plan to become pregnant. This medication may harm an unborn baby and cause problems with normal labor/delivery. It is not recommended for use in pregnancy from 20 weeks until delivery. If your doctor decides that you need to use this medication between 20 and 30 weeks of pregnancy, you should use the lowest effective dose for the shortest possible time. You should not use this medication after 30 weeks of pregnancy.This drug passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

              DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: aliskiren, ACE inhibitors (such as captopril, lisinopril), angiotensin II receptor blockers (such as losartan, valsartan), cidofovir, lithium, methotrexate, corticosteroids (such as prednisone), "water pills" (diuretics such as furosemide).This medication may increase the risk of bleeding when taken with other drugs that also may cause bleeding. Examples include anti-platelet drugs such as clopidogrel, "blood thinners" such as dabigatran/enoxaparin/warfarin, among others.Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (aspirin, NSAIDs such as celecoxib, ibuprofen, or ketorolac). These drugs are similar to diclofenac and may increase your risk of side effects if taken together. However, if your doctor has directed you to take low-dose aspirin to prevent heart attack or stroke (usually 81-162 milligrams a day), you should continue taking the aspirin unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

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

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

              MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

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

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

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

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              Formulary

              FormularyPatient Discounts

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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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.