Pemoline (Cylert™) is a central nervous system stimulant used to treat children with attention defici disorder. There have been scattered reports of hepatotoxicity with Pemoline usually involving transient elevation of liver chemistries. Overt liver failure has been rarely reported. We recently encountered four cases of marked liver dysfunction in children on Pemoline. Two of these progressed to hepatic failure and necessitated liver transplantation.

The patients ranged in age from 6 to 14 years. Two were female. Pemoline dose was 37.5mg daily in three and 75mg daily in one. Duration of medication use ranged from 5 weeks to 4.5 years. The patient who developed symptoms after 5 weeks had taken Pemoline for a 9 month course during the previous year. One patient had careful monitoring of liver chemistries every three months while on the drug. All four presented with jaundice and fatigue. One had fever and one had hepatomegaly on exam. Presenting bilirubin levels ranged from 6-10 mg%, alanine transferase levels were in the 1,000-2,000 range with only mildly elevated alkaline phosphatase and gamma glutamyl transferase levels suggesting severe hepatocellular damage. All had coagulopathy. Two patients spontaneously resolved after drug withdrawal with normalization of liver chemistries over 3-4 months. Two required liver transplantation for severe hepatic synthetic dysfunction and coma. Pathology on the two explanted livers and one patient's percutaneous liver biopsy showed submassive necrosis with bridging fibrosis and chronic active hepatitis consistent with severe drug hepatitis.

All four patients had negative serologies for hepatotrophic viruses and normal evaluations for metabolic causes of liver disease. Three patients had autoimmune markers measured. All three had positive antinuclear antibody titers (1:40, 1:80, 1:320 respectively). One had a borderline anti-histone antibody titer and one had a low titer of anti-parietal cell antibodies. Liver-kidney microsomal antibodies were negative in two and smooth muscle antibodies were negative in three. In conclusion:

  1. 1

    There is strong evidence to consider Pemoline as a potential potent hepatotoxin in children.

  2. 2

    Hepatotoxicity usually occurs many months into Pemoline therapy except upon re-challenge.

  3. 3

    There may be an immunologic component to this hepatotoxicity.

  4. 4

    Routine monitoring of liver chemistries may not prevent serious hepatic complications of Pemoline.