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benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from CYLERT therapy.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 ≥ 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).
CYLERT (pemoline) is a central nervous system stimulant. Pemoline is structurally dissimilar to the amphetamines and methylphenidate.
CYLERT (pemoline) is indicated in Attention Deficit Hyperactivity Disorder (ADHD). Because of its association with life threatening hepatic failure, CYLERT should not ordinarily be considered as first line therapy for ADHD (see BOXED WARNING).
CYLERT (pemoline) therapy should be part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.
Published Studies Related to Cylert (Pemoline)
A randomized controlled trial of pemoline for attention-deficit/hyperactivity disorder in substance-abusing adolescents. [2004.04]
CONCLUSIONS: Pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD.
Effect of fluoxetine, pemoline and placebo on heart period and QT variability in normal humans. [2003.09]
OBJECTIVE: To measure the effects of fluoxetine and pemoline on heart period and QT variability... CONCLUSION: Pemoline, but not fluoxetine, decreases heart period variability (HPV) in the HF power, suggesting a vagolytic effect on cardiac autonomic function. Pemoline is also associated with an increase in QT interval variability, a measure that is sensitive to adrenergic agonists.
Pemoline treatment of adolescents with attention deficit hyperactivity disorder: a short-term controlled trial. [2000.09]
BACKGROUND: Despite the increased recognition of attention deficit hyperactivity disorder (ADHD) in adolescents, few controlled studies have assessed treatments for this age group. Adolescent issues, such as embarrassment at receiving medication at school and experimentation with abusable substances, have accelerated efforts to find effective, well-tolerated treatments beyond traditional stimulants. Pemoline has been found effective for treating both children and adults with ADHD but has not been evaluated in adolescents with ADHD... CONCLUSIONS: These findings resemble those reported in children and adults with ADHD. This trial suggests pemoline is well tolerated and effective in adolescents and may be a particularly useful ADHD treatment for adolescents.
Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder. [1999.06]
Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied.
Intensive and sustained air operations: potential use of the stimulant, pemoline. [1998.07]
BACKGROUND: Intensive and sustained military operations involve long periods of overnight work and the occasional use of a stimulant to maintain performance may be beneficial. In this context a dose response study was carried out to investigate the effects of pemoline, a dopamimetic agent, on overnight work and to assess potential residual effects on subsequent sleep... CONCLUSION: The present studies indicate that a 20 mg dose of pemoline may be suitable for maintaining nocturnal performance without having adverse effects on recovery sleep.
Clinical Trials Related to Cylert (Pemoline)
Pemoline for Cocaine Abuse - 7 [Completed]
Pemoline in the Treatment of Stimulant Dependence - 5 [Withdrawn]
The purpose of this study is to assess the efficacy of pemoline in treating cocaine and/or
methamphetamine dependent adults with comorbid Adult Attention Deficit Hyperactivity
A Pilot Trial of Modafinil for Treatment of Methamphetamine Dependence [Completed]
Patients treated for methamphetamine dependence have high rates of relapse, and no
pharmacotherapy has yet been demonstrated to be efficacious. Modafinil (d,
l-2-[(diphenylmethyl) sulfinyl] acetamide) is a novel wake- and vigilance- promoting agent
that is chemically and pharmacologically dissimilar to CNS stimulants such as the
amphetamines, methylphenidate, and pemoline. It is well tolerated and has low abuse
liability compared to CNS stimulants. Modafinil is FDA approved for a variety of sleep
disorders, may relieve methamphetamine withdrawal symptoms, improves cognitive function, has
been shown to reduce cocaine use in dependent users, and is safe when co-administered with
intravenous methamphetamine. We will conduct a pilot, open-label clinical trial of modafinil
to establish its safety and efficacy as a pharmacotherapy for methamphetamine dependence.
1. Determine the safety of modafinil in the treatment of methamphetamine dependence.
2. Determine the efficacy of modafinil in the treatment of methamphetamine dependence.
3. Assess the effect of modafinil on cognitive function in methamphetamine users.
4. Assess the effect of modafinil on methamphetamine withdrawal symptoms.
5. Compare the validity of a cellular telephone-based reporting system for assessing
medication regimen adherence to conventional electronic medication monitoring.
1. Modafinil will be as safe and well tolerated as placebo in a comparison group from
2. Subjects given modafinil will use less methamphetamine than subjects given placebo.
3. Subjects given modafinil with demonstrate improvements in cognitive function when
compared to subjects given placebo.
4. Subjects given modafinil will have reduced withdrawal symptoms when compared to
subjects given placebo.
5. Adherence will be recorded more accurately by cellular telephone than by conventional
electronic medication monitoring.
Page last updated: 2006-01-31