diclofenac (Rx)

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

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

Next:

Interactions

Interaction Checker

and diclofenac

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            Contraindicated (1)

            • fezolinetant

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

            Serious - Use Alternative (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 (269)

            • acebutolol

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

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

            • aceclofenac

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

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

            • acemetacin

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

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

            • agrimony

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

            • albuterol

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

            • alfalfa

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

            • alfuzosin

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

            • aliskiren

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

            • alpelisib

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

            • alteplase

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

            • American ginseng

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

            • amiloride

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

            • antithrombin alfa

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

            • antithrombin III

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

            • apalutamide

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

            • arformoterol

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

            • argatroban

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

            • artesunate

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

            • asenapine

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

            • aspirin

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

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

            • aspirin rectal

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

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

            • aspirin/citric acid/sodium bicarbonate

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

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

            • atazanavir

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

            • atenolol

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

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

            • atogepant

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

            • avapritinib

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

            • axitinib

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

            • azficel-T

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

            • azilsartan

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

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

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

            • bemiparin

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

            • benazepril

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

            • bendroflumethiazide

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

            • betaxolol

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

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

            • betrixaban

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

            • bimatoprost

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

            • bisoprolol

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

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

            • bivalirudin

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

            • budesonide

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

            • bumetanide

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

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

            • candesartan

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

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

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

            • cannabidiol

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

            • capecitabine

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

            • captopril

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

            • carbenoxolone

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

            • carvedilol

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

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

            • celecoxib

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

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

            • celiprolol

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

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

            • chlorothiazide

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

            • chlorpropamide

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

            • chlorthalidone

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

            • cholestyramine

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

            • choline magnesium trisalicylate

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

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

            • cinnamon

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

            • ciprofloxacin

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

            • citalopram

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

            • clomipramine

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

            • clopidogrel

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

            • cordyceps

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

            • cortisone

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

            • cyclopenthiazide

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

            • cyclosporine

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

            • dabigatran

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

            • dalteparin

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

            • deferasirox

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

            • deferiprone

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

            • defibrotide

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

            • deflazacort

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

            • dexamethasone

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

            • diflunisal

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

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

            • digoxin

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

            • dobutamine

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

            • dong quai

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

            • dopexamine

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

            • doxazosin

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

            • drospirenone

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

            • duloxetine

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

            • edoxaban

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

            • efavirenz

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

            • eltrombopag

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

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

            • emtricitabine

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

            • enalapril

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

            • enoxaparin

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

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • epoprostenol

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

            • eprosartan

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

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

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

            • escitalopram

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

            • esmolol

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

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

            • ethacrynic acid

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

            • etodolac

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

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

            • fenbufen

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

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

            • fennel

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

            • fenoprofen

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

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

            • feverfew

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

            • finerenone

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

            • fish oil triglycerides

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

            • flibanserin

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

            • fluconazole

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

            • fludrocortisone

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

            • fluorouracil

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

            • fluoxetine

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

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

            • flurbiprofen

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

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

            • fluvoxamine

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

            • fondaparinux

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

            • formoterol

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

            • forskolin

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

            • fosinopril

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

            • furosemide

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

            • garlic

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

            • gemfibrozil

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

            • gemifloxacin

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

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glimepiride

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

            • glipizide

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

            • glyburide

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

            • green tea

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

            • heparin

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

            • horse chestnut seed

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

            • hydralazine

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

            • hydrochlorothiazide

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

            • hydrocortisone

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

            • ibrutinib

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

            • ibuprofen

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

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

            • ibuprofen IV

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

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

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

            • imatinib

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

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

            • indapamide

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

            • indomethacin

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

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

            • irbesartan

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

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

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

            • isavuconazonium sulfate

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

            • isoproterenol

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

            • ivacaftor

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

            • ketoconazole

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

            • ketoprofen

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

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

            • ketorolac

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

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

            • ketorolac intranasal

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

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

            • labetalol

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

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

            • latanoprost

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

            • latanoprostene bunod ophthalmic

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

            • lemborexant

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

            • levalbuterol

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

            • levofloxacin

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

            • levoketoconazole

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

            • levomilnacipran

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

            • lisinopril

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

            • lithium

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

            • lomitapide

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

            • lornoxicam

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

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

            • losartan

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

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

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

            • lumacaftor/ivacaftor

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

            • meclofenamate

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

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

            • mefenamic acid

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

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

            • melatonin

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

            • meloxicam

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

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

            • mesalamine

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

            • metaproterenol

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

            • methyclothiazide

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

            • methylprednisolone

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

            • metolazone

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

            • metoprolol

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

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

            • midazolam intranasal

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

            • milnacipran

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

            • mipomersen

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

            • mistletoe

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

            • moexipril

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

            • moxifloxacin

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

            • moxisylyte

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

            • mycophenolate

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

            • nabumetone

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

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

            • nadolol

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

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

            • naproxen

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

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

            • nebivolol

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

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

            • nefazodone

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

            • nettle

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

            • nicardipine

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

            • nitisinone

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

            • norepinephrine

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

            • olmesartan

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

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

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

            • oxaprozin

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

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

            • panax ginseng

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

            • parecoxib

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

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

            • paroxetine

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

            • pau d'arco

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

            • pegaspargase

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

            • peginterferon alfa 2b

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

            • penbutolol

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

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

            • perindopril

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

            • phenindione

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

            • phenoxybenzamine

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

            • phentolamine

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

            • phytoestrogens

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

            • pindolol

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

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

            • pirbuterol

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

            • piroxicam

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

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

            • pivmecillinam

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

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

            • potassium acid phosphate

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

            • potassium chloride

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

            • potassium citrate

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

            • potassium iodide

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

            • pralatrexate

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

            • prasugrel

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

            • prazosin

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

            • prednisolone

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

            • prednisone

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

            • probenecid

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

            • propranolol

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

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

            • protamine

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

            • quinapril

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

            • ramipril

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

            • reishi

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

            • reteplase

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

            • rivaroxaban

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

            • rivastigmine

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

            • rucaparib

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

            • sacubitril/valsartan

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

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

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

            • salicylates (non-asa)

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

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

            • salmeterol

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

            • salsalate

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

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

            • saw palmetto

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

            • sertraline

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

            • Siberian ginseng

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

            • silodosin

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

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

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

            • sodium sulfate/?magnesium sulfate/potassium chloride

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

            • sodium sulfate/potassium sulfate/magnesium sulfate

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

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

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

            • sotalol

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

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

            • sparsentan

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

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

            • spironolactone

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

            • succinylcholine

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

            • sulfadiazine

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

            • sulfasalazine

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

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

            • sulindac

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

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

            • tafluprost

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

            • tazemetostat

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

            • telmisartan

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

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

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

            • temocillin

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

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

            • tenecteplase

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

            • tenofovir DF

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

            • terazosin

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

            • terbutaline

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

            • teriflunomide

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

            • ticagrelor

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

            • ticarcillin

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

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

            • timolol

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

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

            • tinidazole

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

            • tolazamide

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

            • tolbutamide

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

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

            • tolfenamic acid

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

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

            • tolmetin

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

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

            • tolvaptan

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

            • torsemide

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

            • trandolapril

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

            • travoprost ophthalmic

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

            • trazodone

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

            • triamcinolone acetonide injectable suspension

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

            • triamterene

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

            • valsartan

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

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

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

            • venlafaxine

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

            • voclosporin

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

            • vorapaxar

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

            • voriconazole

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

            • vortioxetine

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

            • warfarin

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

            • zanubrutinib

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

            • zotepine

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

            Minor (101)

            • aceclofenac

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

            • acemetacin

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

            • acyclovir

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

            • alendronate

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

            • amikacin

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

            • aminohippurate sodium

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

            • amiodarone

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

            • amobarbital

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

            • anamu

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

            • aspirin

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

            • aspirin rectal

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

            • aspirin/citric acid/sodium bicarbonate

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

            • balsalazide

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

            • bendroflumethiazide

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

            • bosentan

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

            • butabarbital

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

            • butalbital

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

            • carbamazepine

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

            • cefadroxil

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

            • cefamandole

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

            • cefpirome

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

            • celecoxib

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

            • cephalexin

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

            • chlorothiazide

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

            • chlorpropamide

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

            • chlorthalidone

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

            • choline magnesium trisalicylate

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

            • cimetidine

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

            • colestipol

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

            • creatine

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

            • cyclopenthiazide

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

            • danshen

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

            • devil's claw

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

            • diclofenac topical

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

            • diflunisal

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

            • disulfiram

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

            • eplerenone

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

            • etodolac

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

            • etravirine

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

            • felbamate

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

            • fenbufen

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

            • fenoprofen

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

            • feverfew

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

            • flurbiprofen

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

            • furosemide

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

            • ganciclovir

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

            • gentamicin

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

            • hydrochlorothiazide

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

            • ibuprofen

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

            • imidapril

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

            • indapamide

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

            • indomethacin

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

            • ketoprofen

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

            • ketorolac

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

            • ketorolac intranasal

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

            • leflunomide

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

            • lornoxicam

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

            • meclofenamate

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

            • mefenamic acid

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

            • meloxicam

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

            • mesalamine

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

            • methyclothiazide

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

            • metolazone

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

            • metronidazole

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

            • miconazole vaginal

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

            • nabumetone

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

            • naproxen

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

            • nateglinide

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

            • neomycin PO

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

            • nilotinib

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

            • noni juice

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

            • ofloxacin

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

            • oxaprozin

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

            • parecoxib

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

            • paromomycin

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

            • pentobarbital

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

            • phenobarbital

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

            • piroxicam

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

            • primidone

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

            • rifampin

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

            • rifapentine

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

            • rose hips

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

            • ruxolitinib

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

            • ruxolitinib topical

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

            • salicylates (non-asa)

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

            • salsalate

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

            • secobarbital

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

            • streptomycin

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

            • sulfamethoxazole

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

            • sulfasalazine

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

            • sulindac

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

            • ticlopidine

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

            • tobramycin

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

            • tolfenamic acid

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

            • tolmetin

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

            • triamterene

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

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

            • valganciclovir

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

            • valproic acid

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

            • vancomycin

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

            • willow bark

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

            • zafirlukast

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

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            Adverse Effects

            >10%

            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
            Pennsaid topical
            -
            20 mg/gram /actuation(2 %) solution
            diclofenac sodium topical
            -
            1.5 % drops
            diclofenac sodium topical
            -
            1 % gel
            diclofenac sodium topical
            -
            20 mg/gram /actuation(2 %) solution
            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
            -
            3 % gel
            diclofenac sodium topical
            -
            20 mg/gram /actuation(2 %) solution
            diclofenac sodium topical
            -
            3 % gel
            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
            -
            1 % gel
            diclofenac sodium topical
            -
            1 % gel
            diclofenac sodium topical
            -
            1 % gel
            diclofenac sodium topical
            -
            3 % gel
            diclofenac sodium topical
            -
            1.5 % drops
            diclofenac oral
            -
            75 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            100 mg tablet
            diclofenac oral
            -
            75 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            100 mg tablet
            diclofenac oral
            -
            25 mg tablet
            diclofenac oral
            -
            75 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            25 mg tablet
            diclofenac oral
            -
            100 mg tablet
            diclofenac oral
            -
            50 mg tablet
            diclofenac oral
            -
            75 mg tablet
            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

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

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            Patient Education
            diclofenac sodium topical

            DICLOFENAC 3% - TOPICAL

            (dye-KLOE-fen-ak)

            COMMON BRAND NAME(S): Solaraze

            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 using this drug but is more likely if you use 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 use this drug right before or after heart bypass surgery (CABG).Stop using diclofenac and get medical help right away if you notice any of these rare but serious side effects: chest/jaw/left arm pain, shortness of breath, unusual sweating, confusion, weakness on one side of the body, trouble speaking, sudden vision changes.Talk to your doctor or pharmacist about the benefits and risks of using this drug.

            USES: See also Warning section.This medication is used to treat a certain skin condition (actinic keratoses). Diclofenac is known as a nonsteroidal anti-inflammatory drug (NSAID).

            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.This medication is for use on the skin only. Wash and dry your hands before applying the medication. Gently apply enough medication to cover the affected skin well as directed by your doctor, usually 2 times daily. This medication is usually applied for 60 to 90 days. Wash your hands after using, unless you are using this medication to treat the hands.The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, use this medication at the lowest effective dose for the shortest possible time. Do not increase your dose or use this drug more often or for longer than prescribed. Discuss the risks and benefits with your doctor or pharmacist.Do not apply the medication in or around the eyes, open skin wounds, or infected/scraped/burned skin. If you do get the medication in those areas, flush with plenty of water.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.Tell your doctor if your condition lasts or gets worse. It may take up to 30 days after finishing the medication for the skin to completely heal.

            SIDE EFFECTS: See also Warning section.Rash, scaling, dry skin, swelling, or itching may occur at the application site. If any of these effects last or get worse, 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 you have any serious side effects, including: signs of kidney problems (such as change in the amount of urine), symptoms of heart failure (such as swelling ankles/feet, unusual tiredness, unusual/sudden weight gain).Other medications similar to this medication may rarely cause serious bleeding from the stomach or intestines. If you notice any of the following rare but very serious side effects, stop using this medication and get medical help right away: stomach/abdominal pain that doesn't go away, black/bloody stools, vomit that looks like coffee grounds.This drug may rarely cause serious (possibly fatal) liver disease. Get medical help right away if you have any symptoms of liver damage, including: nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.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 using 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 (such as benzyl alcohol), 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, aspirin-sensitive asthma (a history of worsening breathing with runny/stuffy nose after taking aspirin or other NSAIDs), liver disease, stomach/intestine problems (such as bleeding, ulcers), heart disease (such as previous heart attack), high blood pressure, stroke, swelling (edema, fluid retention), diabetes, blood disorders (such as anemia), bleeding/clotting problems, growths in the nose (nasal polyps).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 medicine may rarely cause stomach bleeding. Daily use of alcohol and tobacco while using this medicine may increase your risk for stomach bleeding. Limit alcohol and stop smoking. Ask your doctor or pharmacist about how much alcohol you may safely drink.Your condition may get worse when exposed to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Wear protective clothing when outdoors. Ask your doctor if you should use sunscreen along with this medication.Older adults may be at greater risk for stomach/intestinal bleeding, kidney problems, heart attack, and stroke 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.It is unknown if this form of diclofenac passes into breast milk. 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 valsartan, losartan), cidofovir, corticosteroids (such as dexamethasone, prednisone), lithium, methotrexate, "water pills" (diuretics such as furosemide).This medication may increase the risk of bleeding when used 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 ibuprofen, naproxen, 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: This medicine may be harmful if swallowed. 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, change in the amount of urine, slow/shallow breathing.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood pressure, complete blood count, liver/kidney function) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.

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

            STORAGE: Store at room temperature. Do not freeze. 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 December 2022. Copyright(c) 2023 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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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

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