Lanh Green

Lactic Acidosis in Patients with Diabetes Treated with Metformin

To the Editor: From May 1995, when metformin was introduced in the United States, through June 30, 1996, the Food and Drug Administration (FDA) received reports of lactic acidosis in 66 patients tr...

Troglitazone-induced liver failure: a case study☆

BACKGROUND Troglitazone was removed from the U.S. market because its use was associated with an increased risk of liver failure. We evaluated the clinical features of all cases reported to the Food and Drug Administration and estimated the duration and magnitude of the risk of liver failure associated with continued use of the drug. METHODS Data from cases of liver failure associated with troglitazone use were abstracted and analyzed. The extent of troglitazone use was determined from national marketing data, and the duration of use was estimated with data from a large, multistate, health care company. Survival analysis was performed to estimate monthly incidence rates and the cumulative risk of liver failure. RESULTS Ninety-four cases of liver failure (89 acute, 5 chronic) were reported. Of the acute cases, 58 (67%) were women and only 11 (13%) recovered without liver transplantation. Progression from normal hepatic functioning to irreversible liver injury occurred within 1 month in 19 patients who were indistinguishable clinically from the 70 patients who had an unknown time course to irreversibility, except for the post hoc observation that prior cholecystectomy was less common in those with rapid onset. The incidence of liver failure was elevated from the first through at least the 26th month of troglitazone use. Accounting for case underreporting, the number needed to harm from troglitazone use was between 600 to 1500 patients at 26 months. CONCLUSION The progression to irreversible liver injury probably occurred within a 1-month interval in most patients, casting doubt on the value of monthly monitoring of serum aminotransferase levels as a means of preventing troglitazone-induced acute liver failure. The cumulative risk of hepatic failure increased with continued use.

Gynecomastia and Breast Cancer during Finasteride Therapy

To the Editor: From June 1992, when finasteride (Proscar) was approved for the treatment of prostatic hyperplasia, to February 1995, the Food and Drug Administration (FDA) received reports of gynec...

Serious adverse events in norplant users reported to the food and drug administration's medwatch spontaneous reporting system

Objective To describe serious adverse events in Norplant users from reports submitted to the Food and Drug Administrations (FDA) MedWatch Spontaneous Reporting System. Methods Reports of certain serious adverse events in Norplant users in the United States from February 1991 to December 1993 were reviewed and analyzed. Results From the introduction of Norplant in the United States in February 1991 to December 1993, the FDA received reports of 24 women hospitalized for infections at the insertion site, 14 hospitalized or disabled because of difficulties removing the capsules, 14 hospitalized for stroke, three for thrombotic thrombocytopenia purpura, six for thrombocytopenia, and 39 for pseudotumor cerebri. The comparison of reported rates with expected rates and the relationship of some of these disorders with oral contraceptives raises the suspicion of a causal association with Norplant. Conclusions The FDA has received reports of hospitalization or disability for infections, capsule removal difficulties, stroke, thrombotic thrombocytopenia purpura, thrombocytopenia, and pseudotumor cerebri in Norplant users. Health care professionals need to be trained in Norplant insertion and removal to ensure the proper technique. Studies are needed to determine if stroke, thrombocytopenia, and pseudotumor cerebri are causally related to Norplant use.