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Probenecid: Caution is advised when probenecid is administered concurrently since probenecid increases naproxen plasma concentrations and increases the half-life considerably.
Methotrexate: Decreased elimination of methotrexate. Caution is advised when methotrexate is administered concurrently because of possible enhancement of its toxicity.
Anti-hypertensives: Reduced anti-hypertensive effect. Naproxen and other NSAID drugs can reduce the effect of beta-blockers, ACE inhibitors, and ARBs. Concomitant use of NSAIDs with ACE inhibitors or angiotensin-II receptor antagonists may increase the risk of renal impairment, especially in patients with pre-existing poor renal function.
Cyclosporin: Concurrent use of cyclosporin with an NSAID may increase the risk of renal failure.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs. The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.
Lithium: Decreased elimination of lithium. Inhibition of renal lithium clearance leading to increase in plasma lithium concentration has been reported.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Corticosteroids: Increased risk of GI bleeding or gastrointestinal ulceration.
Anticoagulants: It is considered unsafe to take NSAIDs in combination with anticoagulants such as warfarin or heparin unless under direct medical supervision, as NSAIDs may enhance the effects of anticoagulants. Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined. Due to the plasma protein binding of naproxen, patients simultaneously receiving anticoagulants should be observed for signs of overdosage of these drugs.
Quinolone antibiotics: NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Sulfonamides and hydantoins: Naproxen is highly bound to plasma albumin; thus, it has a theoretical potential for interaction with other albumin-bound drugs such as coumarin-type anticoagulants, sulfonylureas, hydantoins, other NSAIDs and aspirin. Concurrent administration of hydantoin, sulfonamide or sulfonylurea with naproxen should be observed for dose adjustments if required. Caution is advised for concomitant administration of glimepiride or glipizide since interaction has been seen with other non-steroidal agents of this class.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): There is an increased risk of gastrointestinal bleeding when anti-platelet agents and SSRIs are combined with NSAIDs.
