bupivacaine/meloxicam (Rx)

Brand and Other Names:Zynrelef
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Dosing & Uses

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Dosage Forms & Strengths

Bupivacaine/meloxicam

extended-release solution for soft-tissue or periarticular instillation

  • 60mg/1.8mg as 2.3-mL single-dose vial
  • 200mg/6mg as 7-mL single-dose vial
  • 300mg/9mg as 10.5-mL single-dose vial
  • 400mg/12mg as 14-mL single-dose vial
  • Concentration: (29.25mg/0.88mg)/mL
  • Kit contains: 5 vented vial spikes, 10 Luer lock applicators, 10 sterile 3-mL Luer lock syringes, 8 sterile 12-mL Luer lock syringes

Postoperative Analgesia

Indicated as a single dose for postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy, or total knee arthroplasty

Bunionectomy

  • Up to 2.3 mL (bupivacaine 60 mg/meloxicam 1.8 mg); apply to proximal and distal ends (ie, beyond the boney repair) of the wound

Open inguinal herniorrhaphy

  • Up to 10.5 mL (bupivacaine 300 mg/meloxicam 9 mg); apply above and below the fascial repair

Total knee arthroplasty

  • Up to 14 mL (bupivacaine 400 mg/meloxicam 12 mg); apply directly to posterior capsule, the anteromedial tissues and periosteum, and the anterolateral tissues and periosteum after cementation of the components

Dosage Modifications

Renal impairment

  • Mild-to-moderate: Consider reducing dose
  • Severe: Not studied and not recommended
  • Hemodialysis: Meloxicam is not dialyzable; do not exceed maximum recommended meloxicam dose or use with other meloxicam-containing products

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment required
  • Severe: Only use if benefits outweigh the risks; monitor for signs of worsening liver function

Poor CYP2C9 metabolizers

  • Consider dose reduction in patients who are known or suspected poor CYP2C9 metabolizers

Dosing Considerations

Avoid additional use of other local anesthetics within 96 hr following administration

Limitations of use

  • Safety and efficacy not established in highly vascular surgeries (eg, intrathoracic, large multilevel spinal, and head and neck procedures)

Safety and efficacy not established

Consider dose reduction, particularly in those with reduced renal or hepatic function

Next:

Interactions

Interaction Checker

and bupivacaine/meloxicam

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            Contraindicated (1)

            • sodium polystyrene sulfonate

              meloxicam increases toxicity of sodium polystyrene sulfonate by Other (see comment). Contraindicated. Comment: Cases of intestinal necrosis (possibly fatal) described with concomitant sorbitol and sodium polystyrene sulfonate; due to sorbitol in meloxicam oral suspension, coadministration is not recommended.

            Serious - Use Alternative (18)

            • aminolevulinic acid oral

              aminolevulinic acid oral, meloxicam. 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

              meloxicam, 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

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

            • benazepril

              meloxicam, 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.

            • bupivacaine implant

              bupivacaine, bupivacaine implant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid additional local anesthetic administration within 96 hr following bupivacaine implantation. If use of additional local anesthetics is unavoidable based on clinical need, monitor for neurologic and cardiovascular effects related to local anesthetic systemic toxicity.

              bupivacaine, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

            • captopril

              meloxicam, 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

              meloxicam, 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

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

            • ketorolac

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

            • ketorolac intranasal

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

            • lisinopril

              meloxicam, 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.

            • methotrexate

              meloxicam 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

              meloxicam, 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

              meloxicam, 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

              meloxicam 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

              meloxicam, 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.

            • ponesimod

              ponesimod, bupivacaine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.

            • quinapril

              meloxicam, 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.

            Monitor Closely (241)

            • acebutolol

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

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

            • aceclofenac

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

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

            • acemetacin

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

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

            • agrimony

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

            • albuterol

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

            • alfalfa

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

            • alfuzosin

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

            • aliskiren

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

            • alteplase

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

            • American ginseng

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

            • amiloride

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

            • antithrombin alfa

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

            • antithrombin III

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

            • arformoterol

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

            • argatroban

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

            • asenapine

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

            • aspirin

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

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

            • aspirin rectal

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

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

            • aspirin/citric acid/sodium bicarbonate

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

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

            • atenolol

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

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

            • azficel-T

              azficel-T, meloxicam. Other (see comment). Use Caution/Monitor. Comment: Patients taking anticoagulants may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of anticoagulants is not recommended. Decisions regarding continued use or cessation of anticoagulants should be made by a physician.

            • azilsartan

              meloxicam, 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.

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

            • bemiparin

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

            • benazepril

              benazepril, meloxicam. 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.

              bupivacaine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

            • bendroflumethiazide

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

            • bupivacaine liposome

              bupivacaine will increase the level or effect of bupivacaine liposome by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Bupivacaine HCl, when injected immediately before bupivacaine liposome, may impact the pharmacokinetic and/or physicochemical properties when the mg dose of bupivacaine HCl solution exceeds 50% of the bupivacaine liposome dose

            • betaxolol

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

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

            • betrixaban

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

            • bimatoprost

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

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

            • bivalirudin

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

            • budesonide

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

            • bumetanide

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

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

            • candesartan

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

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

            • captopril

              bupivacaine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

              captopril, meloxicam. 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

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

            • dofetilide

              bupivacaine, dofetilide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive cardiac effects.

            • carvedilol

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

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

            • celecoxib

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

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

            • celiprolol

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

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

            • chlorothiazide

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

            • chlorpropamide

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

            • chlorthalidone

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

            • cholestyramine

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

            • choline magnesium trisalicylate

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

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

            • cinnamon

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

            • ciprofloxacin

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

            • clobetasone

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

            • clomipramine

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

            • cordyceps

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

            • cortisone

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

            • cyclopenthiazide

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

            • cyclosporine

              meloxicam, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.

            • dabigatran

              dabigatran and meloxicam 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 meloxicam both increase anticoagulation. Modify Therapy/Monitor Closely.

            • deferasirox

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

            • defibrotide

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

            • deflazacort

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

            • dexamethasone

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

            • diclofenac

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

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

            • diflunisal

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

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

            • digoxin

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

            • dobutamine

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

            • dong quai

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

            • dopexamine

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

            • doxazosin

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

            • drospirenone

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

            • duloxetine

              duloxetine, meloxicam. 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, meloxicam. 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 meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • eltrombopag

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • epoprostenol

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

            • eprosartan

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

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

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

            • ethacrynic acid

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

            • etodolac

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

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

            • fennel

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

            • fenoprofen

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

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

            • feverfew

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

            • fish oil triglycerides

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

            • fludrocortisone

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

            • fluoxetine

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

              fluoxetine, meloxicam. 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

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

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

            • fluvoxamine

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

            • fondaparinux

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

            • formoterol

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

            • forskolin

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

            • fosinopril

              fosinopril, meloxicam. 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

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

            • garlic

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

            • gemifloxacin

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

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glimepiride

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

            • glipizide

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

            • glyburide

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

            • green tea

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

            • heparin

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

            • horse chestnut seed

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

            • hydralazine

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

            • hydrochlorothiazide

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

            • hydrocortisone

              meloxicam, 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 meloxicam 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

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

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

            • ibuprofen IV

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

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

            • imatinib

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

              imatinib, meloxicam. 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

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

            • indomethacin

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

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

            • irbesartan

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

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

            • isoproterenol

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

            • ketoprofen

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

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

            • ketorolac

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

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

            • ketorolac intranasal

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

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

            • labetalol

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

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

            • latanoprost

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

            • levalbuterol

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

            • levofloxacin

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

            • levomilnacipran

              levomilnacipran, meloxicam. 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, meloxicam. 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

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

            • lornoxicam

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

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

            • losartan

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

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

            • meclofenamate

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

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

            • mefenamic acid

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

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

            • mesalamine

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

            • metaproterenol

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

            • methyclothiazide

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

            • methylprednisolone

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

            • metolazone

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

            • metoprolol

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

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

            • milnacipran

              milnacipran, meloxicam. 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, meloxicam. 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

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

            • moexipril

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

            • moxisylyte

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

            • mycophenolate

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

            • nabumetone

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

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

            • nadolol

              nadolol, bupivacaine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Use extreme caution during concomitant use of bupivacaine and antihypertensive agents.

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

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

            • naproxen

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

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

            • nevirapine

              nevirapine will decrease the level or effect of bupivacaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nebivolol

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

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

            • nefazodone

              nefazodone, meloxicam. 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

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

            • nevirapine

              nevirapine will decrease the level or effect of meloxicam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • norepinephrine

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

            • olmesartan

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

              meloxicam 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, meloxicam. 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

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

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

            • panax ginseng

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

            • parecoxib

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

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

            • paroxetine

              paroxetine, meloxicam. 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

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

            • pegaspargase

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

            • penbutolol

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

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

            • perindopril

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

            • phenoxybenzamine

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

            • phentolamine

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

            • phytoestrogens

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

            • pindolol

              pindolol, bupivacaine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Use extreme caution during concomitant use of bupivacaine and antihypertensive agents.

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

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

            • pirbuterol

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

            • propranolol

              propranolol, bupivacaine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Use extreme caution during concomitant use of bupivacaine and antihypertensive agents.

            • piroxicam

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

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

            • pivmecillinam

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

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

            • potassium acid phosphate

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

            • potassium chloride

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

            • potassium citrate

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

            • potassium iodide

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

            • pralatrexate

              meloxicam 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

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

            • prazosin

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

            • prednisolone

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

            • prednisone

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

            • probenecid

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

            • propranolol

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

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

            • protamine

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

            • quinapril

              quinapril, meloxicam. 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, meloxicam. 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

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

            • reteplase

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

            • rivaroxaban

              rivaroxaban, meloxicam. 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 meloxicam by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

            • sacubitril/valsartan

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

              sacubitril/valsartan, meloxicam. 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.

              meloxicam 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)

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

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

            • salmeterol

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

            • salsalate

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

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

            • saw palmetto

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

            • sertraline

              sertraline, meloxicam. 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

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

            • silodosin

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

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              meloxicam, 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 meloxicam 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 meloxicam 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

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

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

            • spironolactone

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

            • succinylcholine

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

            • sulfasalazine

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

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

            • sulindac

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

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

            • tafluprost

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

            • telmisartan

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

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

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

            • tenecteplase

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

            • tenofovir DF

              tenofovir DF, meloxicam. 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

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

            • terbutaline

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

            • ticagrelor

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

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

            • timolol

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

              timolol, bupivacaine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Use extreme caution during concomitant use of bupivacaine and antihypertensive agents.

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

            • tolazamide

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

            • tolbutamide

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

            • tolfenamic acid

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

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

            • tolmetin

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

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

            • tolvaptan

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

            • torsemide

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

            • trandolapril

              trandolapril, meloxicam. 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, meloxicam. 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, meloxicam. 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

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

            • valsartan

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

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

            • vitamin K1 (phytonadione)

              meloxicam increases and vitamin K1 (phytonadione) decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • voclosporin

              voclosporin, meloxicam. 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

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

            • vortioxetine

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

            • warfarin

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

            • zanubrutinib

              meloxicam, 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

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

            Minor (51)

            • aceclofenac

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

            • acemetacin

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

            • acyclovir

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

            • alendronate

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

            • amikacin

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

            • aminohippurate sodium

              meloxicam 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 meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • amobarbital

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

            • anamu

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

            • aspirin

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

            • aspirin rectal

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

            • balsalazide

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

            • bosentan

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

            • butabarbital

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

            • butalbital

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

            • carbamazepine

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

            • cefadroxil

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

            • cefamandole

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

            • cefixime

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

            • cefpirome

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

            • ceftibuten

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

            • celecoxib

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

            • cephalexin

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

            • chlorothiazide

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

            • chlorpropamide

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

            • choline magnesium trisalicylate

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

            • colestipol

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

            • creatine

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

            • cyclopenthiazide

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

            • danshen

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

            • devil's claw

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

            • diclofenac

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

            • diclofenac topical

              diclofenac topical, meloxicam. 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

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

            • disulfiram

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

            • eplerenone

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

            • etodolac

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

            • etravirine

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

            • felbamate

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

            • fenoprofen

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

            • feverfew

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

            • fluconazole

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

            • flurbiprofen

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

            • furosemide

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

            • ganciclovir

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

            • gentamicin

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

            • hyaluronidase

              hyaluronidase, bupivacaine. Other (see comment). Minor/Significance Unknown. Comment: Hyaluronidase hastens the onset of local analgesia and reduces swelling, but increases systemic absorption of anesthetic. This decreases the duration of action and increases incidence of systemic reaction.

            • hydrochlorothiazide

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

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            Adverse Effects

            >10%

            Bunionectomy

            • Dizziness (22%)
            • Incision site edema (17%)
            • Headache (14%)
            • Incision site erythema (13%)
            • Herniorrhaphy H4
            • Headache (13%)

            Total knee arthroplasty

            • Nausea (50%)
            • Vomiting (26%)
            • Constipation (24%)
            • Hypertension (19%)
            • Pyrexia (14%)

            1-10%

            Bunionectomy

            • Bradycardia (8%)
            • Impaired healing (6%)
            • Muscle twitching (6%)
            • Incision site cellulitis (4%)
            • Wound dehiscence (4%)
            • Incision site infection (3%)

            Herniorrhaphy

            • Bradycardia (9%)
            • Dysgeusia (9%)
            • Skin odor abnormal (8%)

            Total knee arthroplasty

            • Leukocytosis (7%)
            • Pruritus (7%)
            • Headache (7%)
            • Headache (7%)
            • Anemia (5%)
            • Hyperhidrosis (5%)
            • Hypotension (5%)
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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
            • The risk of these events following single-dose local application of bupivacaine/meloxicam is uncertain
            • Contraindicated in setting of coronary artery bypass graft (CABG) surgery

            Gastrointestinal risk

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

            Contraindications

            Known hypersensitivity (eg, anaphylactic reactions, serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components

            History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; severe, sometimes fatal, anaphylactic reactions to NSAIDs reported

            Patients undergoing obstetrical paracervical block anesthesia; use of bupivacaine in this technique has resulted in fetal bradycardia and death

            Patients undergoing coronary artery bypass graft (CABG) surgery

            Cautions

            Hepatotoxicity

            • Amide-type local anesthetics (eg, bupivacaine) are metabolized by the liver; use cautiously with hepatic impairment
            • Increased ALT/AST ≥3x ULN reported (rarely) with NSAID use; rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure, reported
            • Inform patients of warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms); if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash), promptly evaluate the patient

            Bupivacaine

            • Prevent dose-related toxicity by assuring proper dose and correct technique
            • Chondrolysis reported with intra-articular infusion of local anesthetics

            Meloxicam

            • Anaphylaxis and aspirin-sensitive asthma
              • May cause anaphylactic reactions in patients with and without known hypersensitivity to meloxicam and in patients with aspirin-sensitive asthma
              • A subpopulation of patients with asthma may have aspirin-sensitive asthma including severe, potentially fatal bronchospasm; these patients also may may have intolerance to other NSAIDs
              • These patients may also be intolerant to other NSAIDs; when used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for exacerbation of asthma symptoms
            • Cardiovascular events
              • Cardiovascular thrombotic events reported with NSAID use
              • Avoid use post myocardial infarction unless benefits outweigh risk; contraindicated in first 10-14 days following CABG
              • Avoid use with severe heart failure unless benefits outweigh risk of worsening heart failure
              • Fluid retention and edema observed in some patients taking NSAIDs
            • Hypertension
              • NSAIDs may impair response to loop and thiazide diuretics; monitor blood pressure
              • May lead to new-onset hypertension or exacerbate existing hypertension
            • GI bleeding, ulceration, and perforation
              • Anemia reported in NSAID-treated patients; this may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis
              • Monitor hemoglobin or hematocrit if signs or symptoms of anemia occur
            • Renal toxicity and hyperkalemia
              • Long-term administration of NSAIDs has resulted in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury
              • Increases in serum potassium concentration, including hyperkalemia, reported with NSAIDs, even in some patients without renal impairment
              • NSAIDs may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation; patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly; these effects are reversible upon discontinuation of the NSAID
              • Meloxicam may hasten progression of renal dysfunction in patients with preexisting renal disease; because some meloxicam metabolites are excreted by the kidney, monitor patients for signs of worsening renal function; correct volume status in dehydrated or hypovolemic patients prior to initiating therapy
            • Skin reactions
              • NSAIDs can cause serious adverse reactions (eg, exfoliative dermatitis, Stevens-Johnson Syndrome [SJS], toxic epidermal necrolysis [TEN], eosinophilia and systemic symptoms [DRESS] syndrome), which can be fatal
              • These serious events may occur without warning; inform patients about signs and symptoms of serious skin reactions
              • 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 is variable in its presentation, other organ systems not noted here may be involved; early manifestations of hypersensitivity, such as fever or lymphadenopathy may be present even though rash is not evident; if such signs or symptoms are present, evaluate the patient immediately and treat as clinically indicated
            • Methemoglobinemia
              • Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition; if local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia recommended
              • Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood; methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death
              • Discontinue any oxidizing agents; depending on severity of signs and symptoms, patients may respond to supportive care, ie, oxygen therapy, hydration; a more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen
            • Masking of inflammation and fever
              • May reduce utility of diagnostic signs in detecting infection by reducing inflammation and fever
            • Fetal toxicity
              • NSAIDs may cause premature closure of fetal ductus arteriosus, oligohydramnios, and neonatal renal impairment

            Drug interaction overview

            • Other local anesthetics
              • If unable to avoid coadministration, monitor for neurologic and cardiovascular adverse effects
              • Toxic effects of local anesthetics are additive; avoid additional local anesthetic within 96 hr after bupivacaine/meloxicam administration
            • Drug-associated methemoglobinemia
              • Avoid coadministration of bupivacaine with other drugs that increase risk of methemoglobinemia
              • Examples of such drugs include nitrates/nitrites (eg, nitric oxide, nitroglycerin, nitroprusside, nitrous oxide); other local anesthetic; certain antineoplastic agents (eg, cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase); certain antibiotics (eg, dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides); antimalarials (eg, chloroquine, primaquine); anticonvulsants (eg, phenobarbital, phenytoin, sodium valproate); and other drugs (eg, acetaminophen, metoclopramide, quinine, sulfasalazine)
            • Drugs interfering with hemostasis
              • Monitor if coadministered
              • Coadministration of NSAIDs with anticoagulants (eg, warfarin), antiplatelet agents (eg, aspirin), or drugs that inhibit serotonin (eg, SSRIs, SNRIs) may increases risk of bleeding
            • Aspirin
              • Monitor for signs and symptoms of GI bleeding
              • Coadministration of NSAIDs and aspirin associated with increased incidence of GI adverse effects compared with when an NSAID is used alone
            • ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers
              • Monitor blood pressure, volume, renal function
              • NSAIDs may decrease antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers
              • Coadministration of NSAIDs with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure, particularly in patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment
            • Effect of NSAIDS on selected drugs
              • Monitor serum levels (if applicable) and adverse effects
              • Digoxin: Coadministration may increase digoxin serum levels
              • Lithium: Coadministration may increase plasma lithium levels
              • Methotrexate: Coadministration may increase risk for methotrexate toxicity (eg, neutropenia, thrombocytopenia, renal dysfunction)
              • Cyclosporine: Coadministration may increase cyclosporine-associated nephrotoxicity
              • Pemetrexed: Coadministration may increase risk of pemetrexed-associated myelosuppression, renal, and GI toxicity
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            Pregnancy & Lactation

            Pregnancy

            Data are unavailable on use of bupivacaine/meloxicam in pregnant females to evaluate drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, data are available on the individual components

            Bupivacaine

            • There are no studies conducted with pregnant females
            • Animal studies
              • Embryofetal deaths were observed with SC administration of bupivacaine to rabbits during organogenesis at a dose equivalent to 1.6 times the maximum recommended human dose (MRHD) of 266 mg; SC administration of bupivacaine to rats from implantation through weaning produced decreased pup survival at a dose equivalent to 1.5 times the MRHD
              • Advise pregnant females of the potential risks to a fetus

            Meloxicam

            • Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive
            • Fetal toxicity
              • Avoid use of NSAIDs in pregnant women at about 30 weeks' gestation and later; NSAIDs increase risk of premature closure of fetal ductus arteriosus at approximately this gestational age
              • Use of NSAIDs at about 20 weeks' gestation or later in pregnancy may also cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
              • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation
              • Oligohydramnios is often, but not always, reversible with treatment discontinuation; complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation
              • In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required
              • If NSAID treatment is necessary between about 20 and 30 weeks' gestation, limit use to the lowest effective dose and shortest duration possible
              • Consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours; discontinue drug if oligohydramnios occurs and follow up according to clinical practice
            • Animal studies
              • 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 meloxicam, resulted in increased preimplantation and postimplantation loss

            Infertility

            • Females
              • Based on the mechanism of action, prostaglandin-mediated NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women
              • Animal studies have shown prostaglandin synthesis inhibitors may disrupt prostaglandin-mediated follicular rupture required for ovulation
              • Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation
              • Consider withdrawal/avoidance of NSAIDs in women who have difficulties conceiving or who are undergoing infertility investigation
            • Males
              • Male rats given meloxicam PO for 35 days had decreased sperm count and motility, and histopathological evidence of testicular degeneration at 0.8 times the MRHD based on BSA comparison

            Lactation

            Data are unavailable on whether drug is present in human milk, or on the effects on breastfed infants, or on milk production

            Animal data

            • Meloxicam is present in milk of lactating rats at concentrations higher than those in plasma
            • Bupivacaine and meloxicam detected in milk of lactating pigs, but only bupivacaine was detected in plasma of piglets

            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

            Bupivacaine: Local amide anesthetic; blocks generation and conduction of nerve impulses presumably by increasing the electrical excitation threshold in the nerve, by slowing nerve impulse propagation, and by reducing the rate of action potential rise

            Meloxicam: Member of oxicam class; inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2

            Absorption

            Peak plasma time

            • Bunionectomy
              • Bupivacaine: 3 hr
              • Meloxicam: 18 hr
            • Herniorrhaphy
              • Bupivacaine: 18 hr
              • Meloxicam: 54 hr
            • Total knee arthroplasty
              • Bupivacaine: 21 hr
              • Meloxicam: 36 hr

            Peak plasma concentration

            • Systemic plasma levels of bupivacaine or meloxicam following application do not correlate with local efficacy
            • Bunionectomy
              • Bupivacaine: 54 ng/mL
              • Meloxicam: 26 ng/mL
            • Herniorrhaphy
              • Bupivacaine: 271 ng/mL
              • Meloxicam: 225 ng/mL
            • Total knee arthroplasty
              • Bupivacaine: 695 ng/mL
              • Meloxicam: 275 ng/mL

            AUC

            • Bunionectomy
              • Bupivacaine: 1,718 hng/mL
              • Meloxicam: 2,079 hng/mL
            • Herniorrhaphy
              • Bupivacaine: 15,524 hng/mL
              • Meloxicam: Not reported
            • Total knee arthroplasty
              • Bupivacaine: 38,173 hng/mL
              • Meloxicam: 19,525 hng/mL

            Distribution

            After bupivacaine and meloxicam have been released and are absorbed systemically, their distribution is expected to be as other bupivacaine formulations or meloxicam oral formulation

            Bupivacaine

            • Depending on route of administration, distribution to some extent to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain

            Meloxicam

            • Protein bound: 99.4%; primarily to albumin
            • Vd: ~10 L

            Metabolism

            Bupivacaine

            • Metabolized primarily by the liver via conjugation with glucuronic acid
            • Metabolites: ~5% converted to the major metabolite, pipecolylxylidine

            Meloxicam

            • Metabolized in liver by CYP2C9 (major) and CYP3A4 (minor)
            • Metabolites (inactive): 5'-Carboxy meloxicam, 5'-hydroxymethyl meloxicam

            Elimination

            Half-life

            • Bupivacaine: 14-15 hr
            • Meloxicam: 22-25 hr

            Excretion

            • Bupivacaine: Mainly excreted by kidneys; 6% unchanged in urine
            • Meloxicam: Predominately excreted as metabolites equally between urine and feces

            Pharmacogenomics

            CYP2C9 activity reduced in individuals with genetic variants (eg, CYP2C9*2 and CYP2C9*3 polymorphisms)

            Limited data found meloxicam

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            Administration

            Incompatibilities

            Bupivacaine/meloxicam is a nonaqueous solution; do not mix with water, saline, or other local anesthetics as the product will become more viscous and difficult to administer

            Topical antiseptic, such as povidone iodine (eg, Betadine); allow antiseptic to dry before local anesthetic administered into site

            When administered in recommended doses and concentrations, does not ordinarily produce irritation or tissue damage

            Compatibilities

            Compatible with all components in the kit, including syringes, Luer lock applicators, vented vial spike, and syringe tip caps

            Surgical mesh materials, including polypropylene (Prolene), Gore-tex, and polyester

            Silicone membranes

            Bone cement

            Metal alloys used in surgical implants

            Soft Tissue or Periarticular Instillation

            Follow instructions in kit and only use supplied syringes and applicators

            Apply solution without a needle into the surgical site following final irrigation and suctioning, and prior to suturing of each layer, when multiple tissue layers are involved

            When bupivacaine/meloxicam comes in contact with moisture in tissues, it becomes more viscous, allowing it to stay in place

            Does not degrade sutures; when using monofilament sutures, ≥3 knots recommended; contact with bupivacaine/meloxicam may cause a single knot to loosen or untie

            DO NOT administer by following routes: Epidural, intrathecal, intravascular or intra-articular, regional nerve blocks, preincisional or preprocedural locoregional anesthetic techniques

            Only apply to tissue layers below the skin incision and not directly onto subdermal layer or the skin

            Use only amount necessary to coat the tissues, such that bupivacaine/meloxicam does not leak from surgical wound after closure

            Potential risk of severe, life-threatening neurological or cardiac toxicity associated with bupivacaine; administer in setting where trained personnel and equipment are available

            Storage

            Store kit in carton at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Protect from moisture and light

            If vial removed from kit, store at controlled room temperature and protect from light

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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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.