Avandia - Warnings & Precautions

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Hepatic Effects:

Another drug of the thiazolidinedione class, troglitazone, was associated with idiosyncratic hepatotoxicity, and very rare cases of liver failure, liver transplants, and death were reported during clinical use. In pre-approval controlled clinical trials in patients with type 2 diabetes, troglitazone was more frequently associated with clinically significant elevations in liver enzymes (ALT> 3X upper limit of normal) compared to placebo. Very rare cases of reversible jaundice were also reported.

In pre-approval clinical studies in 4,598 patients treated with AVANDIA, encompassing approximately 3,600 patient years of exposure, there was no signal of drug-induced hepatotoxicity or elevation of ALT levels. In the pre-approval controlled trials, 0.2% of patients treated with AVANDIA had elevations in ALT >3X the upper limit of normal compared to 0.2% on placebo and 0.5% on active comparators. The ALT elevations in patients treated with AVANDIA were reversible and were not clearly causally related to therapy with AVANDIA.

In postmarketing experience with AVANDIA, reports of hepatitis and of hepatic enzyme elevations to 3 or more times the upper limit of normal have been received. Very rarely, these reports have involved hepatic failure with and without fatal outcome, although causality has not been established. Rosiglitazone is structurally related to troglitazone, a thiazolidinedione no longer marketed in the United States, which was associated with idiosyncratic hepatotoxicity and rare cases of liver failure, liver transplants, and death during clinical use. Pending the availability of the results of additional large, long-term controlled clinical trials and additional postmarketing safety data, it is recommended that patients treated with AVANDIA undergo periodic monitoring of liver enzymes.

Liver enzymes should be checked prior to the initiation of therapy with AVANDIA in all patients.

Therapy with AVANDIA should not be initiated in patients with increased baseline liver enzyme levels (ALT> 2.5X upper limit of normal). In patients with normal baseline liver enzymes, following initiation of therapy with AVANDIA, it is recommended that liver enzymes be monitored every 2 months for the first 12 months, and periodically thereafter. Patients with mildly elevated liver enzymes (ALT levels 2.5X upper limit of normal) at baseline or during therapy with AVANDIA should be evaluated to determine the cause of the liver enzyme elevation.