Arava

Hoechst Marion Roussel's Arava(r) (leflunomide) has been approved by the Food and Drug Administration to treat adult rheumatoid arthritis. A novel immunomodulatory agent, Arava works by inhibiting dihydroorotate dehydrogenase, a critical step in activating autoimmune lymphocytes. Thus, Arava blocks a pathway in the autoimmune response, and as a result, retards damage to the joints. It gives clinicians an advantage by providing alternative antirheumatic therapy when other remittive agents, such as gold compounds, sulfasalazine, steroids and methotrexate, must be discontinued because of poor efficacy or intolerable side effects.

Onset of action is approximately four weeks. Clinical effectiveness is similar to or greater than that reported with methotrexate, sulfasalazine, injectable gold and cyclosporin A. Since the recent trend in treatment of rheumatoid arthritis has been to initiate disease-modifying drugs upon diagnosis, it is crucial for patients to receive treatment in the first one to three years of their disease.

Commonly reported adverse events were rash, GI distress, elevation of liver function tests and reversible alopecia. Arava is contraindicated in patients with liver disease, hepatitis B or C and pregnant women. Special labeling for women of childbearing age states that pregnancy must be avoided during therapy or prior to the completion of drug elimination procedure after Arava treatment. Elimination of Arava can be induced by administering 8 grams of cholestyramine three times a day for 11 days.

Additive side effects may occur with hepatotoxic substances. A combination of Arava and methotrexate may produce a twofold to threefold elevation of liver enzymes. Although NSAIDs were shown to increase levels of Arava, clinical significance of this interaction remains to be seen. Caution should be used in patients receiving rifampin, as Arava levels increase dramatically with multiple doses of rifampin.

Because of its long half-life, it is recommended that patients receive a loading dose of one 100 mg tablet per day for three days. A daily dosing of 20 mg should suffice for maintenance therapy. However, if side effects are not well tolerated, the dose may be decreased to 10 mg daily.

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