Pemoline is a CNS stimulant, which, although structurally different from the amphetamines and methylphenidate, possesses pharmacological activity similar to that of other known stimulants. It has minimal sympathomimetic effects. Although studies indicate that pemoline may act in animals through dopaminergic mechanisms, the exact mechanism and site of action of the drug in man is not known.
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.
Metabolites of pemoline include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar compounds. Pemoline is excreted primarily by the kidneys; approximately 75% of an oral dose is recovered in the urine within 24 hours. Approximately 43% of pemoline is excreted unchanged.
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.
In patients with known hypersensitivity or idiosyncrasy to the drug (see Adverse Effects).
Pemoline is not recommended for children less than 6 years 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.
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.
Long-term effects of pemoline in children have not been well established.
Liver function tests should be performed prior to and periodically during therapy with pemoline. The drug should be discontinued if abnormalities are revealed and confirmed by follow-up tests (see Adverse Effects regarding reports of abnormal liver function tests and jaundice).
Pemoline should be administered with caution to patients with significantly impaired hepatic or renal function.
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.
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.
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.
Elevations of AST (SGOT), ALT (SGPT), and serum LDH have occurred in patients taking pemoline, usually after several months of therapy. These effects appear to be reversible upon withdrawal of the drug, and are thought to be manifestations of a delayed hypersensitivity reaction. There have also been a few reports of jaundice occurring in patients taking pemoline; a causal relationship between the drug and this clinical finding has not been established.
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. CNS stimulants have been reported to 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:
Signs and symptoms of acute pemoline overdosage may include agitation, restlessness, hallucinations, dyskinetic movements and tachycardia. 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.
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.
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.
Each monogrammed, grooved tablet contains: Pemoline 37.5 mg (orange) or 75 mg (tan). Also contains cornstarch and lactose. Alcohol-free, gluten-free, paraben-free, sucrose-free, sulfite-free and tartrazine-free. Bottles of 100.