Additional Reports of Liver Damage and Rezulin Lead to Further Revisions in Use Guidelines

Rezulin has since been removed from the market. This article was posted before Rezulin was removed from the market.

BOSTON — December 4, 1997 — The U.S. Food and Drug Administration this week 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.

Under these latest revisions, the second set to occur in under two months, people taking Rezulin should have liver function testing before beginning the drug, and monthly for the first six months they are on the drug. After the first six months, they should receive liver testing 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.

On November 3, the FDA and the drug's manufacturer first announced changes in the prescribing information for Rezulin, including a new warning and recommendations for monitoring liver function after one month and then at least every three months during the first year a patient takes the drug. In making these changes, the 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, the 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. As a result of these additional findings, the FDA and the manufacturer have increased the frequency of recommended liver function testing.

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.

Rezulin is used in combination with insulin or sulfonylureas in patients with type 2 diabetes (adult-onset diabetes) whose blood glucose levels are not adequately controlled by these other therapies alone.

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 the 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.

Physicians at Joslin currently will continue to prescribe the medication in appropriate cases because the drug is highly effective in lowering blood sugars for some patients. For many of these people, other drugs, including insulin, are either not appropriate or have not achieved the desired levels of glucose control. Joslin physicians will adhere to the manufacturer and FDA recommendations for regular monitoring of liver enzymes and screening for symptoms typical of liver problems.