Medication Treatments for ADHD - Pemoline (Cylert) for ADHD

Written by Lewis Mehl-Madrona, MD, PhD

(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:

1. Liver enzyme changes have occasionally been noted on patients taking Cylert. Baseline liver enzymes are recommended with follow ups at 3-6 months.
2. Persons using alcohol are at higher risk with this medication. Patients with either liver or kidney compromise should not take this medication.
3. SSRI's affect the use of Cylert due to their effects on the liver P450 isoenzymes.
4. Cylert is a useful alternative for patients with cardiovascular disease as it has no effect on this system.
5. Cylert may cause insomnia, appetite suppression, and tics.

Summary Drug Monograph:

Clinical Pharmacology:

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.

Warnings:

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.