Phenothiazines hepatotoxicity

Chlorpromazine is the best known representative of the aliphatic phenothiazines. Although it is considered to be a low potency agent it is still frequently used. It is one of the most sedative antipsychotic agents and is therefore very effective in the treatment of agitated and violent patients. Extrapyramidal effects are seen with a rather low incidence. However it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic function, due to chlorpromazine. Alimemazine and triflupro-mazine are other representatives from this group. 

There is evidence of a significant hepatotoxic effect of the phenothiazines and in persons under age 50, but not over 50 (521). 

Hepatotoxicity may be as frequent with piperidine and piperazine phenothiazines as with chlorpromazine, despite previous suggestions that the toxicity of these compounds is less. 

Jones JK, Van de Carr SW, Zimmerman H, Leroy A. Hepatotoxicity associated with phenothiazines. Psychopharmacol Bull 1983 19(l) 24-7. 

Drug interactions anticonvulsants (phenytoin, barbiturates, carbamazepine) increase the risk of hepatotoxicity by increasing conversion of acetaminophen to toxic metabolites. Isoniazide also increases risk of acetaminophen hepatotoxicity. Acetaminophen may enhance the anticoagulant effect of warfarin with daily doses > 1.3 g for > 1 week. Phenothiazines may increase risk of severe hypothermia with acetaminophen. Cholestyramine resin may decrease the absorption of acetaminophen. 

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