indication

For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and acute gout. Also for the relief of mild to moderate pain and the treatment of primary dysmenorrhea.

pharmacology

Naproxen is a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Naproxen has analgesic and antipyretic properties. As with other NSAIDs, its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.

mechanism of action

The mechanism of action of naproxen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity.

toxicity

ORAL (LD₅₀): Acute: 248 mg/kg [Rat]. 360 mg/kg [Mouse]. Symptoms of overdose include drowsiness, heartburn, indigestion, nausea, and vomiting.

biotransformation

Naproxen is extensively metabolized to 6-0-desmethyl naproxen and both parent and metabolites do not induce metabolizing enzymes.

absorption

Naproxen itself is rapidly and completely absorbed from the GI tract with an in vivo bioavailability of 95%. Although naproxen itself is well absorbed, the sodium salt form is more rapidly absorbed resulting in higher peak plasma levels for a given dose. Food causes a slight decrease in the rate absorption.

half life

The observed terminal elimination half-life is approximately 15 hours.

drug interactions

Acenocoumarol: The NSAID, naproxen, may increase the anticoagulant effect of acenocoumarol.

Alendronate: Increased risk of gastric toxicity

Anisindione: The NSAID, naproxen, may increase the anticoagulant effect of anisindione.

Colesevelam: Bile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.

Cyclosporine: Monitor for nephrotoxicity

Dicumarol: The NSAID, naproxen, may increase the anticoagulant effect of dicumarol.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Lithium: The NSAID, naproxen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Methotrexate: The NSAID, naproxen, may decrease the renal excretion of methotrexate. Increased risk of methotrexate toxicity.

Telmisartan: Concomitant use of Telmisartan and Naproxen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.

Timolol: The NSAID, Naproxen, may antagonize the antihypertensive effect of Timolol.

Trandolapril: The NSAID, Naproxen, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Naproxen is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Naproxen. Monitor for increased bleeding during concomitant thearpy.

Triflusal: The metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of naproxen to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.

Vilazodone: Increased risk of bleeding with concomitant use of NSAIDs with vilazodone.

Warfarin: The antiplatelet effects of naproxen may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.