Cylert (Pemoline)

CYLERT®

Abbott

Pemoline

CNS Stimulant

Action And Clinical Pharmacology: Pemoline is a CNS stimulant, which, although structurally different from the amphetamines and methylphenidate, possesses pharmacological activity similar to that of other known stimulants.

Peak serum levels after single doses are reached within 2 to 4 hours and the serum half-life is approximately 12 hours. Multiple dose studies in adults at several dose levels indicate that steady state is reached in approximately 2 to 3 days.

Indications And Clinical Uses: Attention deficit hyperactivity disorder (ADHD). Because of its association with life-threatening hepatic failure, pemoline should not ordinarily be considered as first-line drug therapy for ADHD (see Warnings).

Pemoline is indicated 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 CNS dysfunction may or may not be warranted.

Attention deficit disorder and hyperkinetic syndrome are among the terms being used to describe the above signs and symptoms. In the past, a variety of terms have been associated with these signs and symptoms including: minimal brain dysfunction, hyperkinetic reaction of childhood, hyperkinetic syndrome, hyperactive child syndrome, minimal brain damage, minimal cerebral dysfunction, and minor cerebral dysfunction.

Contra-Indications: In patients with known hypersensitivity or idiosyncrasy to the drug (see Adverse Effects).

Pemoline should not be administered to patients with impaired hepatic function (see Warnings and Precautions).

Manufacturers’ Warnings In Clinical States: Because of its association with life-threatening hepatic failure, pemoline should not ordinarily be considered as first-line drug therapy for ADHD (see Indications).

Since pemoline’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 pemoline 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 13 cases reported as of May 1996, 11 resulted in death or liver transplantation, usually within 4 weeks of the onset of signs and symptoms of liver failure. The earliest onset of hepatic abnormalities occurred 6 months after initiation of pemoline. 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. It is also not clear if the recommended baseline and periodic liver function testing are predictive of these instances of acute liver failure. Pemoline should be discontinued if clinically significant hepatic dysfunction is observed during its use (see Precautions).

Pemoline is not recommended for children less than 6 years of age since its safety and efficacy in this age group have not been established.

Clinical experience suggests that in psychotic children, administration of pemoline may exacerbate symptoms of behavior disturbance and thought disorder.

Data are inadequate to determine whether chronic administration of pemoline may be associated with growth inhibition; therefore, growth should be monitored during treatment.

Precautions: Drug treatment is not indicated in all cases of the behavioral syndrome characterized by moderate to severe distractibility, short attention span, hyperactivity, emotional lability and impulsivity. It should be considered only in light of the complete history and evaluation of the child. The decision to prescribe 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.

When these symptoms are associated with acute stress reactions, treatment with pemoline is usually not indicated.

Since pemoline’s market introduction, there have been reports of elevated liver enzymes associated with its use. Many of these patients had this increase detected several months after starting pemoline. Most patients were asymptomatic, with increase in liver enzymes returning to normal after pemoline was discontinued. Liver function tests should be performed prior to and periodically during therapy with pemoline. Treatment with pemoline should be initiated only in individuals without liver disease and with normal baseline liver function tests.

The relationship, if any, between reversible elevations in liver function tests and the occurrence of life-threatening hepatic failure in patients on long-term therapy with pemoline is not known. Liver function testing may not predict the onset of acute liver failure. Nonetheless, pemoline should be discontinued if clinically significant liver function test abnormalities are revealed at any time during therapy with this drug (see Warnings).

Pemoline should be administered with caution to patients with significantly impaired renal function.

Long-term effects of pemoline in children have not been well established.

The interaction of 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 pemoline concomitantly with antiepileptic medications.

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.

Pemoline 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 pemoline. There have been isolated reports of transient psychotic symptoms occurring in adults following the long-term misuse of excessive oral doses of pemoline. Pemoline should be given with caution to emotionally unstable patients who may increase the dosage on their own initiative.

Pregnancy and Lactation: Safety for use during pregnancy and lactation has not been established. Although CNS stimulants are seldom indicated after puberty, it should be borne in mind that pemoline should not be used during pregnancy or in women who may become pregnant.

Adverse Reactions: 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 pemoline (see Precautions and Warnings).

There have been isolated reports of aplastic anemia.

Insomnia is the most frequently reported side effect; 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.

Anorexia with 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 3 to 6 months.

Stomach ache, skin rashes, increased irritability, mild depression, nausea, dizziness, headache, drowsiness, and hallucinations have been reported.

A case of elevated acid phosphatase in association with prostatic enlargement has been reported in a 63-year-old male who was treated with pemoline for sleepiness. The acid phosphatase normalized with discontinuation of pemoline and was again elevated with rechallenge.

The following CNS effects have been reported with the use of pemoline: dyskinetic movements of the tongue, lips, face and extremities, nystagmus and nystagmoid eye movements, and convulsive seizures. Literature reports indicate that pemoline may precipitate attacks of Gilles de la Tourette syndrome.

Mild adverse reactions appearing early during the course of treatment with pemoline often remit with continuing therapy. If adverse reactions are of a significant or protracted nature, dosage should be reduced or the drug discontinued.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Signs and symptoms of acute pemoline overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, restlessness, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, dyskinetic movements, tachycardia, hypertension and mydriasis. The treatment for an acute overdosage of pemoline is essentially the same as that for an overdosage of any CNS stimulant.

Management is primarily symptomatic and may include induction of emesis or gastric lavage, sedation, and other appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate the overstimulation already present. If signs and symptoms are not too severe and the patient is conscious, gastric contents may be evacuated followed by activated charcoal and a cathartic. Chlorpromazine has been reported in the literature to be useful in decreasing CNS stimulation and sympathomimetic effects.

Results of studies in dogs indicate that extracorporeal hemodialysis may be useful in the management of pemoline overdosage; forced diuresis and peritoneal dialysis appear to be of little value.

Dosage And Administration: Administer 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 1-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 pemoline 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. Hyperactivity diminishes with age to the point where it remains a serious problem in only a minority, although other major handicaps may be present. Usually, by puberty the need for medication has diminished or is no longer required.

Availability And Storage: 37.5 mg: Each orange, monogrammed, grooved tablet contains: pemoline 37.5 mg. Nonmedicinal ingredients: gelatin, lactose monohydrate, magnesium hydroxide, polyethylene glycol 8 000, purified water, starch, talc and yellow FD&C No. 6 aluminum lake. Alcohol-, gluten-, paraben-, sucrose-, sulfite- and tartrazine-free. Bottles of 100.

75 mg: Each tan, monogrammed, grooved tablet contains: pemoline 75 mg. Nonmedicinal ingredients: gelatin, iron oxide brown, lactose monohydrate, magnesium hydroxide, polyethylene glycol 8 000, purified water, starch and talc. Alcohol-, gluten-, paraben-, sucrose-, sulfite- and tartrazine-free. Bottles of 100.

Store at controlled room temperature 15 to 30°C.

CYLERT® Abbott Pemoline CNS Stimulant

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