indication

For the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults.

pharmacology

Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity.

mechanism of action

The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase-2 (COX-2). Lumiracoxib does not inhibit COX-1 at therapeutic concentrations.

toxicity

Single oral doses in mice and rats resulted in mortality and/or moribundity at doses of 600 mg/kg and 500 mg/kg, respectively. Single intraperitoneal doses in mice and rats results in mortality/moribundity at 750 mg/kg and 1000 mg/kg, respectively. The maximum non-lethal single oral and intraperitoneal dose in mouse was 300 mg/kg and 250 mg/kg, respectively. In the rat it was 150 mg/kg and 250 mg/kg, respectively.

biotransformation

Hepatic oxidation and hydroxylation via CYP2C9. Three major metabolites have been identified in plasma: 4'-hydroxy-lumiracoxib, 5-carboxy-lumiracoxib, and 4'-hydroxy-5-carboxy-lumiracoxib.

absorption

Rapidly absorbed following oral administration, with an absolute oral bioavailablity of 74%.

half life

Terminal half-life is approximately 4 hours.

drug interactions

Acenocoumarol: Lumiracoxib may increase the anticoagulant effect of acenocoumarol.

Anisindione: Lumiracoxib may increase the anticoagulant effect of anisindione.

Dicumarol: Lumiracoxib may increase the anticoagulant effect of dicumarol.

Lithium: The COX-2 inhibitor increases serum levels of lithium

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

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

Tolbutamide: Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Lumiracoxib. Consider alternate therapy or monitor for changes in Lumiracoxib therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.

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

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

Warfarin: Lumiracoxib may increase the anticoagulant effect of warfarin.