terbinafine-hydrochloride and Arava Interactions

Interactions between terbinafine-hydrochloride(terbinafine) and Arava (leflunomide)

terbinafine and leflunomide (Moderate Drug-Drug)

MONITOR: The concomitant or sequential use (without the recommended leflunomide washout period or procedure) of other agents known to induce hepatotoxicity may potentiate the risk of liver injury associated with leflunomide. Elevated liver transaminases, hepatitis, jaundice/cholestasis, hepatic failure, and acute hepatic necrosis have been reported with leflunomide. Liver enzyme elevations were generally mild (2-fold ULN or less) and resolved while continuing treatment. Marked elevations (greater than 3-fold ULN) occurred infrequently and reversed with dose reduction or discontinuation of treatment. However, fatalities associated with severe liver injury have also been reported rarely. Most cases occurred within six months of therapy and in a setting of multiple risk factors including preexisting liver disease and concomitant use of other hepatotoxins.

MANAGEMENT: The use of leflunomide in combination with other potentially hepatotoxic agents (e.g., alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; endothelin receptor antagonists; interferons; nucleoside reverse transcriptase inhibitors; thiazolidinediones; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, HMG-CoA reductase inhibitors, and niacin; herbal products such as kava and echinacea) should be approached with caution. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Baseline and regular monitoring of hepatic function is recommended. If evidence of serious hepatotoxicity occurs (i.e., ALT elevation greater than 3-fold ULN or persistent elevations between 2- and 3-fold ULN despite dose reduction), treatment with leflunomide should be stopped, and cholestyramine or charcoal administered to accelerate elimination of leflunomide's active metabolite from plasma.