------------------------------------------------------
[Editorial note: Abbott Laboratories has issued a Dear Health Care
Professional letter in the U.S. announcing labeling changes for pemoline
(Cylert). Pemoline is a central nervous stimulant indicated in
attention deficity hyperactivity disorder. According to the letter 15
cases of acute liver failure has been reported in association with the
use of pemoline as of December 1998, of which 12 resulted in deaths or
liver transplantation. Apart from the more frequent recommendations for
liver function test monitoring, the new label emphasizes that written
informed consent should be obtained. Pemoline was withdrawn from the U.K
nearly two years ago. The letter has been reproduced below. The Patient
Information/Consent Form and Product Information (labeling) for pemoline
can be obtained by accessing FDA's website: www.fda.gov/medwatch.
Syed Rizwanuddin Ahmad]
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benefit within 3 weeks of completing dose titration, should be withdrawn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:
Cylert (pemoline) Product Information, Abbott Laboratories
Cylert (pemoline) Patient Information/Consent Form, Abbott Laboratories
--
Send mail for the `E-Drug' conference to `e-drug@usa.healthnet.org'.
Mail administrative requests to `majordomo@usa.healthnet.org'.
For additional assistance, send mail to: `owner-e-drug@usa.healthnet.org'.