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Cylert advertisement, 1996. American Journal of Psychiatry, Vol. 153, No. 3. To get your patient's attention, focus on CYLERT® (pemoline) Once-a-day for ADDH (Attention Deficit Disorder with Hyperactivity) * Proven Effective Psychostimulant * Once-A-Day Convenience * Non-Amphetamine Composition * Few Prescribing Restrictions * Minimal Sympathetic Nervous System Effects(1) * Chewable Tablets for Flexibility * Scored Tablets for Titration As with other drugs indicated for ADDH, Cylert has been associated with insomnia, weight loss, growth suppression, dyskinesia, and exacerbation of behavior disorder, especially in psychotic children. In addition, Cylert has been associated with hallucinations, convulsive seizures, and hepatic dysfunction.(1) Baseline and periodic monitoring of hepatic function is indicated. Cylert is contraindicated in patients with impaired hepatic function. Cylert should be discontinued if abnormalities of liver function are detected.(1) For additional information please see full prescribing information. References 1. Cylert package insert, Abbott Laboratories. Please see brief summary of full prescribing information. INDICATIONS AND USAGE ~ Cylert (pemoline) is indicated in Attention Deficit Disorder (ADD) with hyperactivity as an integral 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. CONTRAINDICATIONS ~ Cylert (pemoline) is contraindicated in patients with known hypersensitivity or idiosyncrasy to the drug. Cylert should not be administered to patients with impaired hepatic function (see ADVERSE REACTIONS). WARNINGS ~ Decrements in the predicted growth (i.e., weight gain and/or height) rate have been reported with the long-term use of stimulants in children. Therefore, patients requiring long-term therapy should be carefully monitored. PRECAUTIONS ~ General: Clinical experience suggests that in psychotic children, administration of Cylert may exacerbate symptoms of behavior disturbance and thought disorder. Cylert should be administered with caution to patients with significantly impaired renal function. Laboratory Tests: Liver function tests should be performed prior to and periodically during therapy with Cylert. The drug should be discontinued if abnormalities are revealed and confirmed by follow-up tests. (See ADVERSE REACTIONS regarding reports of abnormal liver function tests, hepatitis and jaundice.) Drug Interactions: The interaction of Cylert (pemoline) with other drugs has not been studied in humans. Patients who are receiving pemoline concurrently with other drugs, especially drugs with CNS activity, should be monitored carefully. Decreased seizure threshold has been reported in patients receiving Cylert concomitantly with antiepileptic medications. Carcinogenesis: Long-term studies have been conducted in rats with doses as high as 150 mg/kg/day for eighteen months. There was no significant difference in the incidence of any neoplasm between treated and control animals. Mutagenesis: Data are not available concerning long-term effects on mutagenicity in animals or humans. Impairment of Fertility: The results of studies in which rats were given 18.75 and 37.5 mg/kg/day indicated that pemoline did not affect fertility in males or females at those doses. Pregnancy: Teratogenic effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses of 18.75 and 37.5 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nonteratogenic effects: Studies in rats have shown an increased incidence of stillbirths and cannibalization when pemoline was administered at a dose of 37.5 mg/kg/day. Postnatal survival of offspring was reduced at doses of 18.74 and 37.5 mg/kg/day. Postnatal survival of offspring was reduced at doses of 18.75 and 37.5 mg/kg/day. Nursing Mothers: It is not known if this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cylert is administered to a nursing woman. Pediatric Use: Safety and effectiveness in children below the age of 6 years have not been established. Long-term effects of Cylert in children have not been established (see WARNINGS). CNS stimulants, including pemoline, have been reported to precipitate motor and phonic tics and Tourette's syndrome. Therefore, clinical evaluation for tics and Tourette's syndrome in children and their families should precede use of stimulant medications. Drug treatment is not indicated in all cases of ADD with hyperactivity and should be considered only in light of complete history and evaluation of the child. The decision to prescribe Cylert (pemoline) should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics. ADVERSE REACTIONS ~ The following are adverse reactions in decreasing order of severity within each category associated with CYLERT: Hepatic: There have been reports of hepatic dysfunction, ranging from asymptomatic reversible increases in liver enzymes to hepatitis, jaundice and life- threatening hepatic failure, in patients taking CYLERT. The occurrence of elevated liver enzymes is not rare and these reactions appear to be reversible upon drug discontinuance. Most patients with elevated liver enzymes were asymptomatic. Although no causal relationship has been established, there have been rare reports of hepatic-related fatalities involving patients taking CYLERT. Hematopoietic: There have been isolated reports of aplastic anemia. Central Nervous System: The following CNS effects have been reported with the use of CYLERT: convulsive seizures: literature reports indicate that CYLERT may precipitate attacks of Gilles de la Tourette syndrome; hallucinations; dyskinetic movements of the tongue, lips, face and extremities; abnormal oculomotor function including nystagmus and oculogyric crisis; mild depression; dizziness; increased irritability; headache; and drowsiness. Insomnia is the most frequently reported side effect of CYLERT; it usually occurs early in therapy prior to an optimum therapeutic response. In the majority of cases it is transient in nature or responds to a reduction in dosage. Gastrointestinal: Anorexia and weight loss may occur during the first weeks of therapy. In the majority of cases it is transient in nature; weight gain usually resumes within three to six months. Nausea and stomach ache have also been reported. Genitourinary: A case of elevated acid phosphatase in association with prostatic enlargement has been reported in a 63 year old male who was treated with CYLERT for sleepiness. The acid phosphatase normalized with discontinuation of CYLERT and was again elevated with rechallenge. Miscellaneous: Suppression of growth has been reported with the long- term use of stimulants in children. (See WARNINGS.) Skin rash has been reported with CYLERT. Mild adverse reactions appearing early during the course of treatment with CYLERT often remit with continuing therapy. If adverse reactions are of a significant or protracted nature, dosage should be reduced or the drug discontinued. DRUG ABUSE AND DEPENDENCE ~ Controlled Substance: CYLERT is subject to control under DEA schedule IV. Abuse: CYLERT failed to demonstrate a potential for self- administration in primates. However, the pharmacologic similarity of pemoline to other psychostimulants with known dependence liability suggests that psychological and/ or physical dependence might also occur with CYLERT. There have been isolated reports of transient psychotic symptoms occurring in adults following the long- term misuse of excessive oral doses of pemoline. CYLERT should be given with caution to emotionally unstable patients who may increase the dosage on their own initiative. OVERDOSAGE ~ Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central nervous system and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, hypertension and mydriasis. Consult with a Certified Poison Control Center regarding treatment for up to date guidance and advice. Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Chlorpromazine has been reported in the literature to be useful in decreasing CNS stimulation and sympathomimetic effects. Efficacy of peritoneal dialysis or extracorporeal hemodialysis for CYLERT overdosage has not been established. DOSAGE AND ADMINISTRATION ~ CYLERT (pemoline) is administered as a single oral dose each morning. The recommended starting dose is 37.5 mg/day. This daily dose should be gradually increased by 18.75 mg at one week intervals until the desired clinical response is obtained. The effective daily dose for most patients will range from 56.25 to 75 mg. The maximum recommended daily dose of pemoline is 112.5 mg. Clinical improvement with CYLERT is gradual. Using the recommended schedule of dosage titration, significant benefit may not be evident until the third or fourth week of drug administration. Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy. Ref. 03-4633-R17-Rev. December, 1995 Abbott Laboratories ~ North Chicago, IL 60064 In May 2005, Abbott voluntarily chose to stop sales and marketing of Cylert in the United States. In October 2005, the FDA ruled "the overall risk of liver toxicity from Cylert and generic pemoline products outweighs the benefits of this drug," after allowing it on the U.S. market for 30 years. |