(1997; 15 pages)
Tolrestat - withdrawn: hepatic necrosis
Argentina. Tolrestat (AlrestinR: Wyeth-Ayerst) is a new aldose-reductase inhibitor indicated in the treatment of complications of serious diabetes such as neuropathy, retinopathy and nephropathy.
In March 1995, the National Pharmacovigilance System received a notification of hepatic necrosis and death in a 41-year old woman patient receiving tolrestat capsules 200 mg per day. The patient died 80 days after the beginning of treatment and 30 days after the drug was withdrawn following the appearance of the first hepatic symptoms (abdominal pain and jaundice).
In October 1996, the manufacturer withdrew tolrestat from the market worldwide following reports of two additional deaths from hepatic necrosis associated with the use of tolrestat (in Canada and Italy), and after reviewing the results of recently completed clinical studies that failed to confirm positive results of earlier clinical trials.
Reference: Communication from the Administracion Nacional de Medicamentos, Alimentos y Technologia Medica (ANMAT), Buenos Aires, 5 November 1996.