United States of America. The manufacturer of troglitazone (Rezulin: Parke-Davis): a drug used to treat type 2 diabetes mellitus (non-insulin dependent diabetes mellitus, or adult onset diabetes): is issuing a nationwide letter to healthcare professionals notifying them of significant new changes that are being made to the labelling and recommended uses for this product.

These changes are being made because new safety information (i.e., further evidence of serious and sometimes fatal liver injury in patients treated with troglitazone) indicates that its use should be limited to patients not adequately controlled by other therapy and should not be used as initial single agent therapy in the treatment of type 2 diabetes. The labelling changes also include recommendations for more extensive monitoring of liver function in patients using troglitazone. A patient information sheet has been added to the labelling and will be available for distribution to patients by pharmacists with each Rezulin prescription.

The FDA and the company agreed to these changes after careful analyses of the drug’s safety profile, drawing upon clinical trials data, post-marketing surveillance data and the recommendations made by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee during a recent meeting. The new labelling and other measures being taken regarding troglitazone are in keeping with the recommendations made by the panel of outside experts.

The letter from the manufacturer specifically notes that:

• Rezulin is no longer indicated to be used as initial single agent therapy.

• Prospective Rezulin patients need to have liver chemistries tested before starting therapy, then monthly during the first year of therapy (rather than just 10 times previously recommended). After the first year of therapy patients should be tested quarterly (rather than “periodically” as previously recommended).

• Within the next few weeks, the company will prepare a patient information sheet with FDA-approved information about the safe and effective use of Rezulin. This patient information sheet will be available for distribution to patients by pharmacists with each Rezulin prescription.

In addition to changes in labelling noted above, a new indication will be added to the labelling for troglitazone for its use in combination with sulfonylureas and metformin in patients whose diabetes is not adequately controlled by the combined use of only these other diabetes drugs. This indication is based on new clinical data evaluated by the agency.

FDA urges patients to consult with their physicians before making any changes in the use of Rezulin. Any adverse reactions associated with the drug should be reported promptly.

[See also Information Exchange Alert No. 66 dated 6 November 1997 and No. 67 dated 4 December 1997, and Pharmaceuticals Newsletter Nos. 9&10, September&October 1998]

Reference: FDA Talk Paper T99-28, 16 June 1999.