esomeprazole/naproxen (Rx)

Brand and Other Names:Vimovo

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

esomeprazole/naproxen

tablet

  • 20mg/375mg
  • 20mg/500mg

Rheumatoid Arthritis

1 tablet PO twice daily at least 30 min before meal

Osteoarthritis

1 tablet PO twice daily at least 30 min before meal

Ankylosing Spondylitis

1 tablet PO twice daily at least 30 min before meal

Dosage Modification

If a dose of omeprazole needs to be < 0 mg/day consider alternate treatment

Severe renal impairment (CrCl <30 mL/min): Use not recommended

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and esomeprazole/naproxen

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            Contraindicated (4)

            • erlotinib

              esomeprazole decreases levels of erlotinib by Other (see comment). Contraindicated. Comment: Concomitant use of proton pump inhibitors with erlotinib should be avoided if possible. Drugs that alter pH of upper GI tract may alter the solubility of erlotinib and reduce its bioavailability. .

            • mavacamten

              esomeprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • nelfinavir

              esomeprazole decreases levels of nelfinavir by unspecified interaction mechanism. Contraindicated. Coadministration may lead to loss of nelfinavir virologic response and development of resistance; mechanism may be CYP2C19 inhibition of nelfinavir conversion to active M8 metabolite, and also PPIs decreasing gastric pH resulting in decreased nelfinavir absorption.

            • rilpivirine

              esomeprazole decreases levels of rilpivirine by increasing gastric pH. Applies only to oral form of both agents. Contraindicated. Concurrent use may cause treatment failure and/or the development of rilpivirine or NNRTI resistance owing to decreased levels.

            Serious - Use Alternative (56)

            • abametapir

              abametapir will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • acalabrutinib

              esomeprazole decreases levels of acalabrutinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Acalabrutinib solubility decreases with increasing gastric pH. Due to the long-lasting effect of PPIs, separation of doses may not eliminate the interaction.

            • aminolevulinic acid oral

              aminolevulinic acid oral, naproxen. 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

              naproxen, 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.

            • apalutamide

              apalutamide will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

              apalutamide will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • apixaban

              naproxen and apixaban both decrease anticoagulation. Avoid or Use Alternate Drug.

            • atazanavir

              esomeprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • benazepril

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

            • captopril

              naproxen, 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.

            • carbamazepine

              carbamazepine will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

            • ceritinib

              esomeprazole will decrease the level or effect of ceritinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • cilostazol

              esomeprazole increases toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Decrease cilostazol dose by 50%; 3,4-dehydrocilostazol, an active metabolite, increased by 69% as a result of omeprazole inhibition of CYP2C19.

            • clopidogrel

              esomeprazole decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs that inhibit CYP2C19. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. .

            • dacomitinib

              esomeprazole will increase the level or effect of dacomitinib by unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use with a PPI decreases dacomitinib concentrations, which may reduce dacomitinib efficacy. Avoid use of PPIs with dacomitinib. As an alternative to PPIs, use locally-acting antacids or an H2-receptor antagonist. Administer at least 6 hours before or 10 hours after taking an H2-receptor antagonist.

            • dasatinib

              esomeprazole will decrease the level or effect of dasatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • digoxin

              esomeprazole will increase the level or effect of digoxin by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • enalapril

              naproxen, 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.

            • enzalutamide

              enzalutamide will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluvoxamine

              fluvoxamine will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

            • fosinopril

              naproxen, 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.

            • ibuprofen

              ibuprofen will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • ibuprofen IV

              ibuprofen IV will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. therapeutic duplication; increased risk of gastric ulceration

              ibuprofen IV and naproxen both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen IV and naproxen both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • idelalisib

              idelalisib will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indinavir

              esomeprazole will decrease the level or effect of indinavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • infigratinib

              esomeprazole will decrease the level or effect of infigratinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • isoniazid

              isoniazid will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

            • itraconazole

              esomeprazole will decrease the level or effect of itraconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • ketoconazole

              esomeprazole will decrease the level or effect of ketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • ketorolac

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

            • ketorolac intranasal

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

            • levoketoconazole

              esomeprazole will decrease the level or effect of levoketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • lisinopril

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

            • lonafarnib

              lonafarnib will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Lonafarnib may increase the AUC and peak concentration of CYP2C19 substrates. If coadministration unavoidable, monitor for adverse reactions and reduce the CYP2C19 substrate dose in accordance with its approved product labeling.

            • mesalamine

              esomeprazole decreases effects of mesalamine by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Applies only to sustained release dosage form.

            • methotrexate

              naproxen 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

              naproxen, 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

              naproxen, 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.

            • neratinib

              esomeprazole will decrease the level or effect of neratinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • nilotinib

              esomeprazole will decrease the level or effect of nilotinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Nilotinib has a pH-dependent solubility and solubility is decreased at higher pH; separating doses may not eliminate this effect because of PPI extended duration of action

            • nisoldipine

              esomeprazole will increase the level or effect of nisoldipine by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • pazopanib

              esomeprazole will decrease the level or effect of pazopanib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Avoid coadministration of pazopanib with drugs that raise gastric pH; consider short-acting antacids in place of PPIs and H2 antagonists; separate antacid and pazopanib dosing by several hours

            • pemetrexed

              naproxen 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

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

            • pexidartinib

              esomeprazole will decrease the level or effect of pexidartinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Avoid coadministration of proton pump inhibitors (PPIs) with pexidartinib. Use H2-receptor antagonists or antacids if needed. When using alternatives to PPIs, administer pexidartinib 2 hr before or after taking locally-acting antacids OR administer pexidartinib at least 2 hr before or 10 hr after taking an H2-receptor antagonist.

            • phenobarbital

              phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • quinapril

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

            • ramipril

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

            • secobarbital

              secobarbital will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • secretin

              esomeprazole, secretin. Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant use of PPIs may cause a hyperresponse in gastrin secretion in response to stimulation testing with secretin, falsely suggesting gastrinoma. The time it takes for serum gastrin concentrations to return to baseline following discontinuation of PPIs is specific to the individual PPI. Temporarily stop esomeprazole treatment at least 14 days before assessing to allow gastrin levels to return to baseline.

            • sofosbuvir/velpatasvir

              esomeprazole will decrease the level or effect of sofosbuvir/velpatasvir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Velpatasvir solubility decreases as gastric pH increases (practically insoluble at pH >5). Coadministration of sofosbuvir/velpatasvir with omeprazole or other PPIs is not recommended. If considered medically necessary, give sofosbuvir/velpatasvir with food 4 hr before omeprazole 20 mg. Use with other PPIs has not been studied.

            • sotorasib

              esomeprazole will decrease the level or effect of sotorasib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

            • sparsentan

              esomeprazole decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Proton pump inhibitors may decrease sparsentan exposure which may reduce efficacy of sparsentan.

            • tacrolimus

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

            • trandolapril

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

            • tucatinib

              tucatinib will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            Monitor Closely (305)

            • acebutolol

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

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

            • aceclofenac

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

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

            • acemetacin

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

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

            • agrimony

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

            • albuterol

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

            • alfalfa

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

            • alfuzosin

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

            • aliskiren

              naproxen 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

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

            • American ginseng

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

            • amiloride

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

            • amitriptyline

              esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • ampicillin

              esomeprazole will decrease the level or effect of ampicillin by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • antithrombin alfa

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

            • antithrombin III

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

            • arformoterol

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

            • argatroban

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

            • armodafinil

              armodafinil will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • asenapine

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

            • aspirin

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

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

            • aspirin rectal

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

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

            • aspirin/citric acid/sodium bicarbonate

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

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

            • atenolol

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

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

            • axitinib

              esomeprazole will increase the level or effect of axitinib by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • azilsartan

              naproxen, 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.

              naproxen 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.

            • belumosudil

              esomeprazole will decrease the level or effect of belumosudil by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with proton pump inhibitors.

            • belzutifan

              belzutifan will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • bemiparin

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

            • benazepril

              benazepril, naproxen. 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.

            • bendamustine

              esomeprazole decreases levels of bendamustine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Consentration of active metabolites may be increased.

            • bendroflumethiazide

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

            • betaxolol

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

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

            • betrixaban

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

            • bimatoprost

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

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

            • bivalirudin

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

            • bortezomib

              bortezomib will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of esomeprazole by increasing metabolism. Use Caution/Monitor.

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

            • bosutinib

              esomeprazole will decrease the level or effect of bosutinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Bosutinib displays pH dependent solubility

            • budesonide

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

              esomeprazole decreases effects of budesonide by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Enteric-coated budesonide dissolves at pH >5.5. Also, dissolution of extended-release budesonide tablets is pH dependent. Coadministration with drugs that increase gastric pH may cause these budesonide products to prematurely dissolve, and possibly affect release properties and absorption of the drug in the duodenum.

            • bumetanide

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

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

            • butabarbital

              butabarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • candesartan

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

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

            • cannabidiol

              esomeprazole will increase the level or effect of cannabidiol by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP2C19 inhibitor.

              cannabidiol will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

            • captopril

              captopril, naproxen. 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.

            • carbamazepine

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

            • carbenoxolone

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

            • carbonyl iron

              esomeprazole will decrease the level or effect of carbonyl iron by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • carvedilol

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

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

            • cefpodoxime

              esomeprazole will decrease the level or effect of cefpodoxime by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • cefuroxime

              esomeprazole will decrease the level or effect of cefuroxime by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • celecoxib

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

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

            • celiprolol

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

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

            • cenobamate

              cenobamate will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              cenobamate will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.

            • chlorothiazide

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

            • chlorpropamide

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

            • chlorthalidone

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

            • choline magnesium trisalicylate

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

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

            • cinnamon

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

            • ciprofloxacin

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

            • citalopram

              esomeprazole will increase the level or effect of citalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Citalopram 20 mg/day is the maximum recommended dose for patients taking CYP2C19 inhibitors because of the risk of QT prolongation.

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

            • clobazam

              esomeprazole will increase the level or effect of clobazam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Dosage adjustment may be required; CYP2C19 inhibitors may result in increased exposure to N-desmethylclobazam (active metabolite).

            • clomipramine

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

            • clozapine

              esomeprazole will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cobicistat

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

            • cordyceps

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

            • cortisone

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

            • crizotinib

              esomeprazole decreases levels of crizotinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that elevate the gastric pH may decrease the solubility of crizotinib and subsequently reduce its bioavailability. However, no formal studies have been conducted. .

            • crofelemer

              crofelemer increases levels of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclopenthiazide

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

            • cyclosporine

              cyclosporine, esomeprazole. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: When used for prolonged periods of time PPIs may cause hypomagnesemia and the risk is further increased when used concomitantly with drugs that also have the same effects.

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

            • dabigatran

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

            • dabrafenib

              esomeprazole will decrease the level or effect of dabrafenib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Drugs that alter upper GI tract pH (eg, PPIs, H2-blockers, antacids) may decrease dabrafenib solubility and reduce its bioavailability

              dabrafenib will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Use alternative if available

            • dalteparin

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

            • deferasirox

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

            • defibrotide

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

            • deflazacort

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

            • dexamethasone

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

            • dextroamphetamine

              esomeprazole, dextroamphetamine. Other (see comment). Use Caution/Monitor. Comment: Reduced gastric acidity caused by proton pump inhibitors decreases time to Tmax for amphetamine and dextroamphetamine. AUC was unaffected. .

            • diazepam intranasal

              esomeprazole will increase the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • dichlorphenamide

              dichlorphenamide and naproxen both decrease serum potassium. Use Caution/Monitor.

              dichlorphenamide and esomeprazole both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

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

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

            • digoxin

              esomeprazole increases toxicity of digoxin by Other (see comment). Use Caution/Monitor. Comment: Prolonged use of PPIs may cause hypomagnesemia and increase risk for digoxin toxicity.

            • diflunisal

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

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

            • digoxin

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

            • dobutamine

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

            • dong quai

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

            • dopexamine

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

            • doxazosin

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

            • drospirenone

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

            • duloxetine

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

              esomeprazole will decrease the level or effect of duloxetine by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • edoxaban

              edoxaban, naproxen. 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 decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.

              elagolix will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eltrombopag

              esomeprazole will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, naproxen. 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.

            • escitalopram

              esomeprazole will increase the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • emtricitabine

              emtricitabine, naproxen. 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, naproxen. 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 naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • epoprostenol

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

            • eprosartan

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

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • esmolol

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

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

            • ethacrynic acid

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

            • etodolac

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

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

            • etravirine

              esomeprazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              etravirine will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              fedratinib will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

            • fennel

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

            • fenoprofen

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

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

            • ferric gluconate

              esomeprazole will decrease the level or effect of ferric gluconate by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ferric maltol

              esomeprazole will decrease the level or effect of ferric maltol by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ferrous fumarate

              esomeprazole will decrease the level or effect of ferrous fumarate by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ferrous gluconate

              esomeprazole will decrease the level or effect of ferrous gluconate by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ferrous sulfate

              esomeprazole will decrease the level or effect of ferrous sulfate by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • feverfew

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

            • fexinidazole

              fexinidazole will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of naproxen 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.

            • fluconazole

              fluconazole will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • fludrocortisone

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

            • fluoxetine

              fluoxetine, naproxen. 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 naproxen both increase anticoagulation. Use Caution/Monitor.

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

            • fluvoxamine

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

            • fondaparinux

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

            • formoterol

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

            • forskolin

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

            • fosamprenavir

              esomeprazole will decrease the level or effect of fosamprenavir by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • fosinopril

              fosinopril, naproxen. 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.

            • fosphenytoin

              esomeprazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • furosemide

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

            • garlic

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

            • gefitinib

              esomeprazole decreases levels of gefitinib by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Avoid coadministration of gefitinib with PPIs if possible. If treatment with a PPI is required, separate gefitinib and PPI doses by 12 hr.

            • gemifloxacin

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

            • gentamicin

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

            • ginger

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

            • ginkgo biloba

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

            • glimepiride

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

            • glipizide

              esomeprazole will increase the level or effect of glipizide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

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

            • glyburide

              esomeprazole will increase the level or effect of glyburide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

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

            • green tea

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

            • iloperidone

              iloperidone increases levels of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • heparin

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

            • horse chestnut seed

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

            • hydralazine

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

            • hydrochlorothiazide

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

            • hydrocortisone

              naproxen, 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 naproxen 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.

            • imatinib

              imatinib, naproxen. 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.

            • imipramine

              esomeprazole will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • indapamide

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

            • indomethacin

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

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

            • irbesartan

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

              naproxen 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, naproxen. 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.

            • iron dextran complex

              esomeprazole will decrease the level or effect of iron dextran complex by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • iron sucrose

              esomeprazole will decrease the level or effect of iron sucrose by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • isoproterenol

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

            • istradefylline

              istradefylline will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ketoprofen

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

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

            • ketorolac

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

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

            • ketorolac intranasal

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

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

            • labetalol

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

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

            • latanoprost

              latanoprost, naproxen. 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, naproxen. 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).

            • ledipasvir/sofosbuvir

              esomeprazole decreases levels of ledipasvir/sofosbuvir by Other (see comment). Use Caution/Monitor. Comment: Ledipasvir solubility decreases as pH increases; drugs that increase gastric pH are expected to decrease levels of ledipasvir; proton-pump inhibitor doses comparable to omeprazole <20 mg can be administered simultaneously with ledipasvir/sofosbuvir under fasted conditions.

            • lenacapavir

              lenacapavir will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • letermovir

              letermovir increases levels of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levalbuterol

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

            • levofloxacin

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

            • levomilnacipran

              levomilnacipran, naproxen. 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, naproxen. 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

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

            • lornoxicam

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

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

            • losartan

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

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

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, esomeprazole. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

              lumacaftor/ivacaftor will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lumacaftor/ivacaftor is a strong CYP3A4 inhibitor and also has the potential to induce CYP2C19 and both induce and inhibitor P-gp.

            • meclofenamate

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

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

            • mefenamic acid

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

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

            • melatonin

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

            • meloxicam

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

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

            • mesalamine

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

            • metaproterenol

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

            • methotrexate

              esomeprazole increases levels of methotrexate by decreasing renal clearance. Use Caution/Monitor. Increased risk of toxicity with higher doses.

            • methyclothiazide

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

            • methylphenidate

              esomeprazole decreases effects of methylphenidate by enhancing GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Since the characteristics of methylphenidate extended release capsules (Ritalin LA) are pH dependent, coadministration of antacids or acid suppressants could alter the release of methylphenidate. Consider separating the administration of the antacid and the methylphenidate extended-release capsules may be avoided.

            • methylprednisolone

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

            • metolazone

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

            • metoprolol

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

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

            • milnacipran

              milnacipran, naproxen. 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, naproxen. 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

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

            • mitotane

              mitotane decreases levels of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • moexipril

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

            • moxisylyte

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

            • mycophenolate

              esomeprazole will decrease the level or effect of mycophenolate by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor. Potential interaction applies to mycophenolate mofetil. Enteric coated mycophenolate sodium formulation is less sensitive to this interaction. Clinical significance unclear.

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

            • nabumetone

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

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

            • pentobarbital

              pentobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • nadolol

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

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

            • nebivolol

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

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

            • nefazodone

              nefazodone, naproxen. 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

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

            • norepinephrine

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

            • olmesartan

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

              naproxen 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, naproxen. 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.

            • ospemifene

              naproxen, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

            • oxaprozin

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

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

            • panax ginseng

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

            • parecoxib

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

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

            • paroxetine

              paroxetine, naproxen. 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

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

            • pegaspargase

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

            • peginterferon alfa 2b

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

            • penbutolol

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

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

            • perindopril

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

            • phenobarbital

              phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • phenoxybenzamine

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

            • phentolamine

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

            • phenytoin

              esomeprazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • phytoestrogens

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

            • pindolol

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

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

            • pirbuterol

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

            • piroxicam

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

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

            • pivmecillinam

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

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

            • polysaccharide iron

              esomeprazole will decrease the level or effect of polysaccharide iron by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • posaconazole

              esomeprazole will decrease the level or effect of posaconazole by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

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

            • potassium acid phosphate

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

            • potassium chloride

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

            • potassium citrate

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

            • potassium iodide

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

            • pralatrexate

              naproxen 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

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

            • prazosin

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

            • prednisolone

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

            • prednisone

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

            • primidone

              primidone will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • probenecid

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

            • propranolol

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

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

            • protamine

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

            • quinapril

              quinapril, naproxen. 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, naproxen. 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

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

            • reteplase

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

            • rifampin

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

              rifampin will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • riociguat

              esomeprazole will decrease the level or effect of riociguat by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • ritonavir

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

            • rivaroxaban

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

            • rose hips

              esomeprazole will decrease the level or effect of rose hips by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • sacubitril/valsartan

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

              sacubitril/valsartan, naproxen. 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.

              naproxen 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)

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

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

            • salmeterol

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

            • salsalate

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

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

            • saw palmetto

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

            • secobarbital

              secobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • sertraline

              sertraline, naproxen. 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

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

            • silodosin

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

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              naproxen, 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 naproxen 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 naproxen 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

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

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

            • sparsentan

              sparsentan will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates.

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

            • St John's Wort

              St John's Wort will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              St John's Wort will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • spironolactone

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

            • stiripentol

              stiripentol will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • succinylcholine

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

            • sulfasalazine

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

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

            • sulindac

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

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

            • tacrolimus

              esomeprazole will increase the level or effect of tacrolimus by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Concomitant administration may increase tacrolimus whole blood concentrations, particularly in intermediate or poor metabolizers of CYP2C19

            • tafluprost

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

            • tazemetostat

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

            • telmisartan

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

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

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

            • tenecteplase

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

            • tenofovir DF

              tenofovir DF, naproxen. 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

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

            • terbutaline

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

            • ticarcillin

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

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

            • timolol

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

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

            • tobramycin inhaled

              tobramycin inhaled and naproxen both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolazamide

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

            • tolbutamide

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

              esomeprazole will increase the level or effect of tolbutamide by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

            • tolfenamic acid

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

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

            • triclabendazole

              triclabendazole will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

            • tolmetin

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

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

            • tolvaptan

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

            • torsemide

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

            • trandolapril

              trandolapril, naproxen. 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, naproxen. 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, naproxen. 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

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

            • valsartan

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

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

            • vismodegib

              esomeprazole will decrease the level or effect of vismodegib by Other (see comment). Use Caution/Monitor. Drugs that increase gastric pH alter vismodegib solubility and therefore reduce bioavailability; effect on efficacy unknown

            • vitamin K1 (phytonadione)

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

            • voclosporin

              voclosporin, naproxen. 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

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

            • voriconazole

              voriconazole will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • vortioxetine

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

            Minor (116)

            • aceclofenac

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

            • acemetacin

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

            • acetazolamide

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

            • acyclovir

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

            • alendronate

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

            • alosetron

              esomeprazole will decrease the level or effect of alosetron by increasing metabolism. Minor/Significance Unknown.

            • alprazolam

              esomeprazole increases levels of alprazolam by decreasing metabolism. Minor/Significance Unknown.

            • ambrisentan

              esomeprazole will increase the level or effect of ambrisentan by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • amikacin

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

            • aminohippurate sodium

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

            • anamu

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

            • anastrozole

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

            • aspirin

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

            • aspirin rectal

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

            • balsalazide

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

            • bismuth subsalicylate

              esomeprazole increases levels of bismuth subsalicylate by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • blessed thistle

              blessed thistle decreases effects of esomeprazole by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction.

            • bosentan

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

            • capecitabine

              esomeprazole decreases effects of capecitabine by unknown mechanism. Minor/Significance Unknown. Retrospective data suggest elevated gastric pH caused by PPI use may impair capecitabine tablet dissolution and/or reduce absorption. However, a randomized crossover study found esomeprazole did not affect capecitabine systemic exposure.

            • cefadroxil

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

            • cefamandole

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

            • cefpirome

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

            • ceftibuten

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

            • celecoxib

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

            • cephalexin

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

            • chlordiazepoxide

              esomeprazole will increase the level or effect of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

            • chlorothiazide

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

            • chlorpropamide

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

            • choline magnesium trisalicylate

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

            • clomipramine

              esomeprazole will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • clonazepam

              esomeprazole will increase the level or effect of clonazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • creatine

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

            • cyanocobalamin

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

            • cyclopenthiazide

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

            • cyclophosphamide

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

            • danshen

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

            • darifenacin

              darifenacin will decrease the level or effect of esomeprazole by Other (see comment). Minor/Significance Unknown. Effectiveness of proton pump inhibitors may be decreased theoretically if administered with other antisecretory agents

            • devil's claw

              devil's claw decreases effects of esomeprazole by pharmacodynamic antagonism. Minor/Significance Unknown.

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

            • dexamethasone

              dexamethasone will decrease the level or effect of esomeprazole by increasing metabolism. Minor/Significance Unknown.

            • diclofenac

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

            • diazepam

              esomeprazole will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • diclofenac topical

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

            • dronedarone

              dronedarone will increase the level or effect of esomeprazole by decreasing metabolism. Minor/Significance Unknown.

            • efavirenz

              efavirenz will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, esomeprazole. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Based on drug interaction studies conducted with the components of Stribild, no clinically significant drug interactions have been either observed or are expected when coadministered with PPIs.

            • eplerenone

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

            • eslicarbazepine acetate

              eslicarbazepine acetate decreases levels of esomeprazole by increasing metabolism. Minor/Significance Unknown. Monitor for GI symptoms; net increased or decreased effect on PPI action unclear due to opposing CYP450 actions.

            • estazolam

              esomeprazole will increase the level or effect of estazolam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • etodolac

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

            • fenoprofen

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

            • ferric carboxymaltose

              esomeprazole will decrease the level or effect of ferric carboxymaltose by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.

            • feverfew

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

            • fluoxetine

              fluoxetine will increase the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • flurazepam

              esomeprazole increases levels of flurazepam by decreasing metabolism. Minor/Significance Unknown.

            • flurbiprofen

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

            • fluvastatin

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

            • furosemide

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

            • ganciclovir

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

            • gentamicin

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

            • hydrochlorothiazide

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

            • imidapril

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

            • indapamide

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

            • indomethacin

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

            • itraconazole

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

            • ketoprofen

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

            • ketorolac

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

            • ketorolac intranasal

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

            • larotrectinib

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

            • levoketoconazole

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

            • levothyroxine

              esomeprazole decreases levels of levothyroxine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

            • liothyronine

              esomeprazole decreases levels of liothyronine by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

            • liotrix

              esomeprazole decreases levels of liotrix by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

            • lisdexamfetamine

              esomeprazole, lisdexamfetamine. Other (see comment). Minor/Significance Unknown. Comment: Reduced gastric acidity caused by proton pump inhibitors decreases time to Tmax for amphetamine and dextroamphetamine. AUC was unaffected. .

            • lorazepam

              esomeprazole increases levels of lorazepam by decreasing metabolism. Minor/Significance Unknown.

            • lornoxicam

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

            • meclofenamate

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

            • mefenamic acid

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

            • meloxicam

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

            • mesalamine

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

            • methamphetamine

              esomeprazole decreases levels of methamphetamine by Other (see comment). Minor/Significance Unknown. Comment: Time to maximum concentration (Tmax) of amphetamine is decreased compared to when administered alone; monitor patients for changes in clinical effect and adjust therapy based on clinical response.

            • methyclothiazide

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

            • metolazone

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

            • midazolam

              esomeprazole increases levels of midazolam by decreasing metabolism. Minor/Significance Unknown.

            • nabumetone

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

            • neomycin PO

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

            • nitazoxanide

              nitazoxanide, naproxen. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

            • noni juice

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

            • ofloxacin

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

            • oxaprozin

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

            • parecoxib

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

            • paromomycin

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

            • phytoestrogens

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

            • piroxicam

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

            • ponatinib

              esomeprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.

            • ribociclib

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

            • rose hips

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

            • salicylates (non-asa)

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

            • salsalate

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

            • streptomycin

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

            • sulfasalazine

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

            • sulindac

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

            • theophylline

              esomeprazole increases toxicity of theophylline by Other (see comment). Minor/Significance Unknown. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • thyroid desiccated

              esomeprazole decreases levels of thyroid desiccated by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown. Conflicting evidence regarding this interaction exists.

            • tobramycin

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

            • tolfenamic acid

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

            • tolmetin

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

            • triamterene

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

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

            • triazolam

              esomeprazole increases levels of triazolam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • valganciclovir

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

            • vancomycin

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

            • voriconazole

              esomeprazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • willow bark

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

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            Adverse Effects

            >10%

            Gastric erosion (19%); compared with 38% for equal naproxen dose without PPI

            Dyspepsia (18%); compared with 27% for equal naproxen dose without PPI

            Gastritis (17%)

            1-10%

            Diarrhea (6%)

            Abdominal pain (6%)

            Nausea (5%)

            Hiatal hernia (4%)

            Abdominal distension (4%)

            Flatulence (4%)

            Esophagitis (4%)

            Constipation (3%)

            Headache (3%)

            Dysgeusia (2%)

            Erosive duodenitis (2%)

            Hemorrhagic gastritis (1%)

            <1%

            GERD

            Duodenal ulcer

            Erosive esophagitis

            Postmarketing reports

            Gait disturbance

            Abdominal distension

            Gastroesophageal reflux

            Hematochezia

            Contusion

            Fall

            Joint swelling

            Muscle spasms

            Renal tubular necrosis

            Naproxen

            • Body as a Whole: Angioneurotic edema, menstrual disorders
            • Cardiovascular: Congestive heart failure, vasculitis, pulmonary edema
            • Gastrointestinal: Inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, and obstruction of the upper or lower gastrointestinal tract, esophagitis, stomatitis, hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
            • Hepatobiliary: Hepatitis (some cases have been fatal)
            • Hemic and Lymphatic: Eosinophilia, hemolytic anemia, aplastic anemia
            • Metabolic and Nutritional: Hyperglycemia, hypoglycemia
            • Nervous System: Depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions
            • Respiratory: Eosinophilic pneumonitis
            • Dermatologic: Alopecia, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa.
            • Special Senses: Hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema
            • Urogenital: Glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine
            • Reproduction (female): Infertility

            Esomeprazole

            • Blood and Lymphatic: Agranulocytosis
            • Eye: Blurred vision
            • Gastrointestinal: Pancreatitis, microscopic colitis, fundic gland polyps
            • Hepatobiliary: Hepatic failure, hepatitis with or without jaundice
            • Immune System: Anaphylactic reaction/shock
            • Infections and Infestations: GI candidiasis, Clostridium difficile associated diarrhea
            • Metabolism and Nutritional Disorders: Hypomagnesemia, hypocalcemia, hyponatremia, and/or hypokalemia
            • Musculoskeletal and Connective Tissue: Muscular weakness, myalgia, bone fracture
            • Nervous System: Hepatic encephalopathy
            • Psychiatric: Aggression, agitation, hallucination
            • Renal and Urinary: Interstitial nephritis
            • Reproductive System and Breast: Gynecomastia
            • Respiratory, Thoracic, and Mediastinal: Bronchospasm
            • Skin and Subcutaneous Tissue: Alopecia, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP)
            • Nutrition: Cyanocobalamin (vitamin B-12) deficiency
            • Acute tubulointerstitial nephritis
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            Warnings

            Black Box Warnings

            Cardiovascular Risk

            • 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 risk factors for or existing cardiovascular disease may be at greater risk
            • NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI and stroke)

            Gastrointestinal Risk

            • NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
            • GI adverse events may occur at any time during use and without warning symptoms
            • Elderly patients are at greater risk for serious GI events

            Contraindications

            Hypersensitivity, including angioedema and anaphylactic reaction/shock has been reported with esomeprazole

            Asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs

            NSAIDs are contraindicated in late-stage pregnancy (risk for closure of ductus arteriosus)

            NSAIDs are contraindicated for perioperative pain in setting of CABG surgery

            Perioperative pain in the setting of coronary artery bypass graft surgery

            Concomitant administration with rilpivirine-containing products

            Cautions

            Anaphylactic reactions reported; seek emergency help if anaphylactic reaction occurs

            NSAIDs increase risk for hypertension (or worsening hypertension) and CHF; therapy can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to increased incidence of CV events; patients taking angiotensin-converting enzyme (ACE) inhibitors, thiazides diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs; monitor blood pressure (BP) during initiation of NSAID treatment and throughout course of therapy

            Fluid retention and edema have been observed in some patients treated with NSAIDs; use of naproxen may blunt CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers; avoid use in patients with severe heart failure unless benefits expected to outweigh risk of worsening heart failure; if this medication is used in patients with severe heart failure, monitor patients for signs and symptoms of worsening heart failure

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

            Inhibits platelet aggregation

            PPIs may increase risk of osteoporosis-related fractures

            Relief of symptoms does not eliminate the possibility of a gastric malignancy; consider additional follow-up and diagnostic testing in adult patients who have suboptimal response or early symptomatic relapse after completing treatment with a PPI

            PPIs possibly associated with increased incidence of Clostridium difficile-associated diarrhea (CDAD); consider diagnosis of CDAD for patients taking PPIs with diarrhea that does not improve

            Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) reported with PPIs; avoid using for longer than medically indicated; discontinue if signs or symptoms consistent with CLE or SLE are observed and refer patient to specialist; most patients improve with discontinuation of PPI alone in 4-12 weeks; serological testing (e.g. ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations

            PPIs decreased gastric acidity increases serum chromogranin A (CgA) levels and may cause false-positive diagnostic results for neuroendocrine tumors; temporarily discontinue PPIs before assessing CgA levels

            Acute interstitial nephritis reported in patients taking PPIs; may occur at any point during PPI therapy and is generally attributed to idiopathic hypersensitivity reaction; discontinue therapy if acute interstitial nephritis develops

            Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B12) caused by hypo-or achlorhydria; rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy reported

            Patients with advanced renal disease should be adequately hydrated

            If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, discontinue treatment and monitor patient

            May elevate and/or prolong serum concentrations of methotrexate and/or its metabolite when administered concomitantly with PPIs, possibly leading to toxicity; consider a temporary withdrawal of PPI therapy with high-dose methotrexate administration

            Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including, may delay or prevent rupture of ovarian follicles that may lead to reversible infertility in some women; consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing investigation of infertility

            PPI therapy is associated with increased risk of fundic gland polyp; risk increases with long-term use >1 year; patient may be asymptomatic; problem usually identified incidentally on endoscopy; use shortest duration of therapy appropriate to condition being treated

            Acute tubulointerstitial nephritis (TIN) reported in patients taking PPIs; may occur at any point during PPI therapy; patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia); in reported case series, some patients were diagnosed on biopsy and in absence of extra-renal manifestations (eg, fever, rash or arthralgia); discontinue therapy and evaluate patients with suspected acute TIN

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

            Anemia has occurred in NSAID-treated patients; this may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis; if a patient treated has any signs or symptoms of anemia, monitor hemoglobin or hematocrit

            Therapy may increase risk of bleeding events; co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (eg, aspirin), and serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase risk; monitor these patients for signs of bleeding

            The pharmacological activity of this medication in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections

            Cardiovascular thrombotic events

            • NSAIDs increase risk for thrombotic events (eg, MI, stroke); consistent evidence does not exist that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events; concurrent use of aspirin and an NSAID, such as naproxen, increases risk of serious gastrointestinal (GI) events
            • Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDS; the relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease; however, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate; some observational studies found that this increased risk of serious CV thrombotic events began as early as first weeks of treatment; the increase in CV thrombotic risk has been observed most consistently at higher doses
            • To minimize potential risk for adverse CV event in NSAID-treated patients, use lowest effective dose for shortest duration possible; physicians and patients should remain alert for development of such events, throughout entire treatment course, even in absence of previous CV symptoms; patients should be informed about symptoms of serious CV events and steps to take if they occur
            • Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in first week of treatment; although the absolute rate of death declined somewhat after first-year post-MI, increased relative risk of death in NSAID users persisted over at least next four years after follow-up
            • Avoid use in patients with a recent MI unless benefits are expected to outweigh risk of recurrent CV thrombotic events; if this drug is used in patients with a recent MI, monitor patients for signs of cardiac ischemia

            Gastrointestinal bleeding, ulceration, and perforation

            • NSAIDs, including naproxen, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal; these serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs; only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic; however, even short-term NSAID therapy is not without risk
            • Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors; other factors that increase risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status
            • Most postmarketing reports of fatal GI events are in elderly or debilitated patients; additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding; NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated
            • Strategies to minimize GI risks in NSAID-treated patients
              • Use lowest effective dosage for shortest possible duration.
              • Avoid administration of more than one NSAID at a time
              • Avoid use in patients at higher risk unless benefits are expected to outweigh increased risk of bleeding; for such as patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs
              • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
              • If serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue therapy until serious GI adverse event is ruled out
              • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

            Hepatotoxicity

            • Elevations of ALT or AST (three or more times upper limit of normal [ULN]) reported; in addition, rare, and sometimes fatal, cases of severe hepatic injury, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure reported
            • Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including naproxen
            • 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, etc.), discontinue this drug immediately, and perform clinical evaluation of patient
            • This drug should be avoided in patients with severe hepatic impairment

            Renal toxicity and hyperkalemia

            • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury; renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation
            • Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure,liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly; discontinuation of NSAID therapy was usually followed by recovery to the pretreatment state
            • .No information is available from controlled clinical studies regarding use of this medication in patients with advanced renal disease; the renal effects of therapy may hasten the progressionof renal dysfunction in patients with pre-existing renal disease
            • Correct volume status in dehydrated or hypovolemic patients prior to initiating therapy; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration,or hypovolemia during use of this medication
            • Avoid use of this medication in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal failure; if this medication is used in patients with advanced renal disease, monitor patients for signs of worsening renal function
            • Hyperkalemia
              • Increases in serum potassium concentration, including hyperkalemia, reported with use of NSAIDs, even in some patients without renal impairment; in patients with normal renalfunction, these effects have been attributed to a hyporeninemic-hypoaldosteronism state

            Hypomagnesemia and mineral metabolism

            • Hypomagnesemia may occur with prolonged use (ie, >1 year); adverse effects may result and include tetany, arrhythmias, or seizures; hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients
            • In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI; in 25% of cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued
            • For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically
            • Consider monitoring magnesium and calcium levels prior to initiation of therapy and periodically while on treatment in patients with a preexisting risk of hypocalcemia (eg, hypoparathyroidism)
            • Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing therapy

            Skin and skin reactions

            • NSAIDs can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal
            • PPIs can cause severe cutaneous adverse reactions, SJS, TEN, and acute generalized exanthematous pustulosis (AGEP); these serious events may occur without warning
            • Inform patients about signs and symptoms of serious skin reactions and discontinue therapy at first appearance of skin rash or any other sign of hypersensitivity; this medication is contraindicated in patients with previous serious skin reactions to NSAIDs

            Drug reaction with eosinophilia and systemic symptoms (DRESS)

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

            Pregnancy

            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 weeks and 30 weeks gestation, limit use to lowest effective dose and shortest duration possible; consider ultrasound monitoring of amniotic fluid if treatment is needed in a pregnant woman; discontinue therapy if oligohydramnios occurs and follow up according to clinical practice

            There are no studies on effects of therapy during labor or delivery; in animal studies, NSAIDs, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase incidence of stillbirth

            Esomeprazole

            • There are no human data for esomeprazole; however, available epidemiologic data for omeprazole (esomeprazole is the S-isomer of omeprazole) fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use
            • In animal studies with administration of oral esomeprazole magnesium in rats, changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole
            • When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age

            Infertility

            • Based on mechanism of action, the use of prostaglandin-mediated NSAIDs may delay or prevent rupture of ovarian follicles that may lead to reversible infertility in some women
            • Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation; published animal studies have shown that administration of prostaglandin synthesis inhibitors have the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
            • Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing investigation of infertility

            Lactation

            Limited data from published literature report that naproxen anion has been found in milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma; esomeprazole is the S-isomer of omeprazole and limited data from published literature suggest omeprazole may be present in human milk; there is no information on effects of naproxen or omeprazole on breastfed infant or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition

            Lactation: Naproxen is distributed in breast milk, not recommended

            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

            Naproxen: NSAID that inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis; has antipyretic and analgesic effects

            Esomeprazole: S-isomer of omeprazole, a proton pump inhibitor; inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells

            Naproxen

            Half-Life: 13-15 hr

            Bioavailability: 95%

            Duration: 4-7 hr

            Onset: 1 hr

            Distribution: 0.16 L/kg

            Peak Serum Time: 1.5-3 hr; high fat meal prolongs Tmax by 10 hr

            Peak Plasma Concentration: 62-96 mcg/mL Vd: 0.16 L/kg

            Protein Bound: >99% albumin

            Metabolism: hepatic via CYP2C9, CYP1A2; also undergoes hepatic conjugation

            Clearance: 0.13 L/min/kg

            Excretion: feces < 3%, urine 95%

            Esomeprazole

            Half-Life: 1.2-1.5 hr

            Bioavailability: 90%, food decreases AUC by 33-53%

            Duration: 17 hr gastric acid inhibition at steady state

            Onset: 1-2 hr

            Peak Plasma Time: 1-1.6 hr

            Vd: 16 L

            Protein Bound: 97%

            Clearance: 9-16 L/hr

            Excretion: Feces 20%, urine 80%

            Metabolism

            • Extensively by hepatic P450 enzyme: major metabolic pathway is via CYP2C19, the rest is via CYP3A4
            • Slow metabolizers (3% of Caucasians and African-Americans) are deficient in CPY2C19 enzyme system, plasma concentration can be higher than those with the enzyme present
            • CYP2C19 inhibitor
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            Administration

            Oral Administration

            Tablet consists of immediate-release esomeprazole layer and enteric-coated naproxen core

            Swallow whole; do not chew, crush, dissolve, or split

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            Images

            No images available for this drug.
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            Patient Handout

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

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.