indication

Used to relieve the inflammation, swelling, stiffness, and joint pain associated with rheumatoid arthritis and osteoarthritis.

pharmacology

Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain.

mechanism of action

Anti-inflammatory effects of Oxaprozin are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Oxaprozin is a non-selective NSAID, with a cell assay system showing lower COX-2 selectivity implying higher COX-1 selectivity.

toxicity

Oral, mouse: LD₅₀ = 1210 mg/kg; Oral, rabbit: LD₅₀ = 172 mg/kg; Oral, rat: LD₅₀ = 4470 mg/kg

biotransformation

Hepatic. Ester and ether glucuronide are the major conjugated metabolites of oxaprozin, and do not have significant pharmacologic activity.

absorption

Oxaprozin is 95% absorbed after oral administration. Food may reduce the rate of absorption of oxaprozin, but the extent of absorption is unchanged. Antacids do not significantly affect the extent and rate of oxaprozin absorption.

half life

54.9 hours

route of elimination

Oxaprozin is expected to be excreted in human milk based on its physical-chemical properties; however, the amount of oxaprozin excreted in breast milk has not been evaluated. Approximately 95% of oxaprozin is metabolized by the liver. Approximately 5% of the oxaprozin dose is excreted unchanged in the urine. Sixty-five percent (65%) of the dose is excreted in the urine and 35% in the feces as metabolite. Biliary excretion of unchanged oxaprozin is a minor pathway. Several oxaprozin metabolites have been identified in human urine or feces.

drug interactions

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

Alendronate: Increased risk of gastric toxicity

Anisindione: The NSAID, oxaprozin, may increase the anticoagulant effect of anisinodione.

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, oxaprozin, may increase the anticoagulant effect of dicumarol.

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

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

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

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

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

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

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