FDA posts safety alerts, public health advisories, press releases and other notices from companies as a service to health professionals, consumers and other interested parties. Although FDA approves medical products, FDA does not endorse either the product or the company.

Dear Health Care Professional:

This communication is to advise you of an update to the WARNINGS section in the labeling for CYLERT (pemoline, Abbott), a central nervous system stimulant indicated for the treatment of attention deficit hyperactivity disorder (ADHD). Although there has been no change in the reported rate of acute hepatic failure associated with CYLERT use, based on discussions with the Food and Drug Administration (FDA), the labeling has been revised to provide updated recommendations for liver function monitoring and a "Patient Information/Consent" form.

Before prescribing CYLERT, the physician should be thoroughly familiar with the details of the CYLERT prescribing information. CYLERT should not be prescribed until there has been a complete discussion of the risks with the patient. The "Patient Information/Consent" form should be reviewed with any patient currently taking CYLERT or any new patient for whom CYLERT is to be prescribed. In addition, written informed consent should be obtained.

The revised black box warning reads as follows:

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). Because CYLERT provides an observable symptomatic benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from CYLERT therapy. Since CYLERT's marketing in 1975, 15 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 portion of actual cases were recognized and reported, the risk could be substantially higher. Of the 15 cases reported as of December 1998, 12 resulted in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure. The earliest 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 symptoms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice. Treatment with CYLERT should be initiated only in individuals without liver disease and with normal baseline liver function tests. It is not clear if baseline and periodic liver function testing are predictive of these instances of acute liver failure; however, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended: Serum ALT (SGPT) levels should be determined at baseline, and every two weeks thereafter. If CYLERT therapy is discontinued and then restarted, liver function test monitoring should be done at baseline and reinitiated at the frequency above. CYLERT should be discontinued if serum ALT (SGPT) is increased to a clinically significant level, or any increase greater than or equal to 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure (see PRECAUTIONS). The physician who elects to use CYLERT should obtain written informed consent from the patient prior to initiation of CYLERT therapy (see PATIENT INFORMATION/CONSENT FORM).

Changes consistent with the revised black box warning have been made to the PRECAUTIONS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections of the labeling. An enlarged copy of the Patient Information/Consent Form and a full copy of the revised package insert are enclosed. A supply of Patient Information/Consent Forms may be obtained, free of charge, by calling (847) 937-7302. Permission to use the enclosed Patient Information/Consent Form by photocopy reproduction is also hereby granted by Abbott Laboratories.

As with all medical products, health care professionals are strongly encouraged to report any serious adverse events that occur with the use of Cylert (pemoline) either to Abbott Laboratories (1-800-633-9110), or to the FDA's MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178), via the MedWatch website at www.fda.gov/medwatch, or mail (using postage-paid form) to MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787.

If you have any questions, please contact our Medical Services Department at 1-800-633-9110.

Sincerely,

David Pizzuti, M.D.
Divisional Vice President
Medical Affairs

Enclosures: