Because of its association with life threatening hepatic failure, CYLERT should not ordinarily be considered as first line drug therapy for ADHD (see INDICATIONS AND USAGE).

Since CYLERT´s marketing in 1975, 13 cases of acute hepatic failure have been reported to the FDA. While the absolute number of reported cases is not large, the rate of reporting ranges from 4 to 17 times the rate expected in the general population. This estimate may be conservative because of under reporting and because the long latency between initiation of CYLERT treatment and the occurrence of hepatic failure may limit recognition of the association. If only a por-tion of actual cases were recognized and reported, the risk could be substantially higher.

Of the 13 cases reported as of May 1996, 11 resulted in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure. The ear-liest onset of hepatic abnormalities occurred six months after initiation of CYLERT. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symp-toms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice. It is also not clear if the recom-mended baseline and periodic liver function testing are predictive of these instances of acute liver failure. CYLERT should be dis-continued if clinically significant hepatic dysfunction is observed during its use (see PRECAUTIONS).