Hepatotoxicity Due to Pemoline

Abstract

Pemoline, a central nervous system stimulant, has been used extensively in Great Britain and Europe for a variety of conditions including memory failure and depression. In the 10 years that the drug has been used no report of hepatotoxicity has appeared. A prospective study of efficacy and safety of pemoline was started in the United States approximately 3 years ago. This report describes two patients who developed reversible liver abnormalities while receiving pemoline during the study and following rechallenge with the drug.

Four Cases of Severe Hepatotoxicity Associated With Pemoline: Possible Autoimmune Pathogenesis

“…3,4,10 The possibility of a drug-induced autoimmune mechanism is suggested by the presence of autoantibodies in the 3 patients of ours who were tested. As with our third patient, rechallenge can bring about relatively rapid hepatic inflammation, suggesting some sort of sensitization process.…”

“…3,4 This led to recommendations that patients on pemoline have their liver chemistries followed several times a year. The earliest reports were of mild, asymptomatic elevations of liver chemistries that usually responded well to drug withdrawal.…”

“…3,4 Nehra et al 8 thought that the often long latency period between pemoline introduction and hepatic injury could be explained by metabolic idiosyncrasy. Noting that there was rapid recurrence of elevated liver chemistries on drug rechallange, an idiosyncratic hypersensitivity reaction was first postulated.…”

Pemoline Therapy Resulting in Liver Transplantation

“…Tolman et al 2 first described two cases of adults with elevated AST concentrations after 8 weeks of pemoline 150 mg/d. Liver enzymes returned to normal after discontinuation of the medication.…”

Bone mineral status measured by direct photon absorptiometry in institutionalized adults receiving long-term anticonvulsant therapy and multivitamin supplementation

“…The effects of anticonvulsant drugs on epileptic patients differ widely, with biochemical evidence of osteomalacia or deficient bone mineral varying from 4 to 75% [1][2][3][4][5][6][7][8][9][10][11][12]. Factors which influence the effect that anticonvulsant drugs have on bone mineral include the dose of the drug, combination of drugs, and duration of therapy [2, 6, 7, 9, 10, 12], the amount of physical activity [8], exposure to sunlight [2, 6,8], and nutrition, especially in regard to vitamin D supplemented foods [6,10].…”