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.
Information for Patients
Patients should be informed that CYLERT therapy has been associated with liver abnormalities ranging from reversible liver function test increases that do not cause any symptoms to liver failure, which may result in death. Patients should be informed that the risk of liver failure in the general population is relatively rare; however patients taking CYLERT are at a greater risk of developing liver failure than that expected in the general population. At present, there is no way to predict who is likely to develop liver failure; however only patients without liver disease and with normal baseline liver function tests should initiate CYLERT therapy. Patients should be advised to follow their doctors directives for liver function tests prior to and during CYLERT therapy. Patients should be advised to be alert for signs of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they should occur.
The physician who elects to use CYLERT should obtain written informed consent from patients prior to initiation of CYLERT therapy (see PATIENT INFORMATION/CONSENT FORM.)
Laboratory Tests
Since CYLERT'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 CYLERT. Most patients were asymptomatic, with the increase in liver enzymes returning to normal after CYLERT was discontinued.
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 BOXED WARNING).
Drug Interactions
The interaction of CYLERT (pemoline) with other drugs has not been studied in humans. Patients who are receiving CYLERT 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 18.75 and 37.5 mg/kg/day.
Nursing Mothers
It is not known whether 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 ADHD 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.
Geriatric Use
Clinical studies of CYLERT did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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