Medication Treatments for ADHD - Pemoline (Cylert) for ADHD
(Pemoline (Cylert) is no longer available in the U.S.)
Cylert ranks third in sales for the treatment of ADHD. Cylert is manufactured by Abbott; no generic is available.
Unlike other stimulant medications Cylert has an onset of action of about an hour and must be taken for 1-2 weeks before improvement occurs. It is recommended that the dosage of this medication be increased in increments of 18.75mg every 2-3 days over several weeks. Cylert is more expensive than Ritalin or Dexedrine.
Important points about Cylert:
- Liver enzyme changes have occasionally been noted on patients taking Cylert. Baseline liver enzymes are recommended with follow ups at 3-6 months.
- Persons using alcohol are at higher risk with this medication. Patients with either liver or kidney compromise should not take this medication.
- SSRI's affect the use of Cylert due to their effects on the liver P450 isoenzymes.
- Cylert is a useful alternative for patients with cardiovascular disease as it has no effect on this system.
- Cylert may cause insomnia, appetite suppression, and tics.
Summary Drug Monograph:
Cylert (pemoline) has a pharmacological activity similar to that of other known central nervous system stimulants; however, 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.
There is neither specific evidence which clearly establishes the mechanism whereby Cylert produces its mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.
Pemoline is rapidly absorbed from the gastrointestinal tract, Approximately 50% is bound to plasma proteins. The serum half-life of pemoline is approximately 12 hours. Peak serum levels of the drug occur within 2 to 4 hours after ingestion of a single dose. Multiple dose studies in adults at several dose levels indicate that steady state is reached in approximately 2 to 3 days. In animals given radiolabeled pemoline, the drug was widely and uniformly distributed throughout the tissues, including the brain.
Pemoline is metabolized by the liver. Metabolites of pemoline include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar compounds. Cylert is excreted primarily by the kidneys with approximately 50% excretedunchanged and only minor fractions present as metabolites.
Cylert (pemoline) has a gradual onset of action. Using the recommended schedule of dosage titration, significant clinical benefit may not be evident until the third or fourth week of drug administration.
Dosage and Aministration:
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. ufficient to require continued therapy.
Because of its association with life threatening hepatic failure, Cylert should not ordinarily be considered as first line drug therapy for ADHD.
Since Cylerts'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 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 13 cases reported as of May 1996, 11 resulted in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure. The ear-liest 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 symp-toms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice. It is also not clear if the recom-mended baseline and periodic liver function testing are predictive of these instances of acute liver failure. Cylert should be dis-continued if clinically significant hepatic dysfunction is observed during its use.
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
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.
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. Liver function tests should be performed prior to and periodically during therapy with Cylert. Treatment with Ctlert should be initiated only in individual 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 Cylert is not known. Liver function testing may not predict the onset of acute liver failure. Nonetheless, Cylert should be discontinued if clinically significant liver function test abnormalities are revealed at any time during therapy with this drug
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.
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: abnorrnal 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.
Miscellaneous: Suppression of growth has been reported with the long- term use of stimulants in children. 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.
Staff, H. (2003, December 1). Medication Treatments for ADHD - Pemoline (Cylert) for ADHD, HealthyPlace. Retrieved on 2021, January 17 from https://www.healthyplace.com/adhd/articles/medication-treatments-for-adhd-pemoline-cylert-for-adhd