Warnings from new Rezulin package liner

Rezulin (troglitazone) tablets

WARNINGS

  • Hepatotoxicity.

    Severe idiosyncratic hepatocellular injury has been reported during marketed use. The hepatic injury is usually reversible, but very rare cases of hepatic failure, leading to death or liver transplant, have been reported.

    During all clinical studies in North America, a total of 48 of 2,510 (1.9%) Rezulin-treated patients and three of 475 (0.6%) placebo-treated patients had alanine transaminase levels greater than three times the upper limit of normal. Nineteen patients (0.8%) had ALT over 8x ULN; five patients (0.2%) had ALT values over 30x ULN. Twenty of the Rezulin-treated and one of the placebo-treated patients were withdrawn from treatment. Two of the 20 Rezulin-treated patients developed reversible jaundice; one of these patients had a liver biopsy, which was consistent with an idiosyncratic drug reaction. An additional Rezulin-treated patient had a liver biopsy, which was also consistent with idiosyncratic drug reaction.

    Serum ALT levels should be checked at the start of therapy, at least monthly for the first year of Rezulin therapy, and at least quarterly thereafter. Rezulin therapy should not be initiated if the patient has a history of liver disease, clinical evidence of acute liver disease, alcohol abuse, or increased serum ALT levels (ALT> 1.5 times the upper limit of normal). (See CONTRAINDICATIONS.) Liver function tests should also be obtained for patients at the first symptoms suggestive of hepatic dysfunction, fatigue, anorexia, nausea, vomiting, abdominal pain, dark urine, or jaundice. If serum transaminase levels are moderately increased (ALT> 1.5 to 2 times the upper limit of normal), liver function tests should be repeated immediately and then weekly until the levels return to normal. If at any time a patient has jaundice or ALT rises above three times the upper limit of normal, Rezulin should be discontinued.

    INDICATIONS AND USAGE

    Rezulin is indicated to improve glycemic control in patients with Type 2 diabetes mellitus as an adjunct to diet and exercise in combination with (not substituted for):

  • a sulfonylurea drug for patients who are not adequately controlled with a sulfonylurea alone;

  • a sulfonylurea drug together with metformin for patients who are not adequately controlled with the combination of a sulfonylurea and metformin;

  • Insulin in patients who are not adequately controlled with insulin alone. Rezulin is not indicated as initial therapy in patients with Type 2 diabetes.

    CONTRAINDICATIONS

    Rezulin is contraindicated in patients with known hypersensitivity or allergy to Rezulin or any of its components. Rezulin therapy should not be initiated if the patient has a history of liver disease, or exhibits clinical evidence of active liver disease, cirrhosis, hepatitis, history of alcohol abuse, or increased serum transaminase levels (ALT> 1.5 times the upper limit of normal).