T97-61 Marian Segal: 301-827-6242 December 1, 1997 Consumer Hotline: 800-532-4440 PATIENT TESTING AND LABELING STRENGTHENED FOR REZULIN The U.S. Food and Drug Administration today announced that patients taking the diabetes drug Rezulin (troglitazone) should be monitored more frequently for signs of injury to the liver. In addition, warning information about potential liver toxicity will be more prominently featured in the drug's labeling. These actions, taken with the full cooperation of the drug's manufacturer, re-emphasize for health care providers and patients the importance of monitoring patients taking Rezulin to ensure that it is used in the safest manner. Rezulin is used in combination with insulin or sulfonylurea in patients with type II diabetes (adult-onset diabetes mellitus) whose blood glucose levels are not adequately controlled by these other therapies alone. On November 3, FDA and the drug's manufacturer announced changes in the prescribing information for Rezulin, including a new warning and recommendations for monitoring liver function. In making these changes, FDA was aware of approximately 35 post-marketing reports of liver injury among U.S. and Japanese patients taking Rezulin, including liver failure leading to one liver transplant and one death. At that time, FDA asked for reports on additional adverse events associated with the use of Rezulin, and the agency has now received a total of approximately 150 adverse event reports, including three deaths from liver failure linked to the use of Rezulin in Japan. Approximately 600,000 patients in the U.S. and 200,000 in Japan have been treated with this drug. The deaths in Japan occurred in patients treated before the stronger label warning and recommendation for liver enzyme testing took effect there. FDA has concluded that liver enzyme levels should be measured in patients taking Rezulin at the start of therapy, every month for the first six months of treatment, every other month for the next six months, and periodically thereafter. In addition, liver function tests should be performed on any patient on Rezulin who develops symptoms of liver dysfunction, such as nausea, vomiting, fatigue, loss of appetite, or dark urine and jaundice. The product's current labeling advises that patients with significant elevation of these liver enzymes stop taking the drug. Previously, liver enzyme testing was recommended during the first two months of therapy and then every three months. The increased monitoring of patients taking Rezulin is designed to detect those few patients in whom use of the drug can lead to serious liver damage. Warner-Lambert, the manufacturer of the drug, will send a letter within the next week to U.S. health care professionals to inform them of these changes. While Rezulin was being studied in patients before FDA approval, approximately two percent of all patients were found to develop elevation of liver enzymes in the blood. These elevations, which serve as markers of potential liver injury, were mostly mild, unassociated with symptoms, and usually resolved when the drug was discontinued. Although FDA will carefully monitor and evaluate reports of liver problems associated with Rezulin, at present the agency continues to find the benefits outweigh the risks for treating appropriately selected and monitored type-2 diabetes patients with Rezulin. Type 2 diabetes is a serious, life-threatening disease that affects 18 million Americans. It is a leading cause of coronary heart disease, blindness, kidney failure, and limb amputation. Adequate control of blood sugar appears to be the most important means of preventing these complications. ####