Carbapenems in the management of valproic acid overdose

Abstract

Severe valproic acid (VPA) overdose is characterized by coma (sometimes with cerebral oedema), respiratory depression, hypotension and metabolic abnormalities. Traditional management of VPA poisoning has been limited to gastrointestinal decontamination, L-carnitine supplementation and, in severe cases, haemodialysis. Recently, interest has developed in the use of carbapenem antibiotics as an adjunctive therapy in patients with severe VPA poisoning. Carbapenems inhibit acylpeptide hydrolase, the enzyme responsible for reconstituting VPA from VPA-glucuronide, and transiently promote distribution of VPA into erythrocytes. In patients receiving VPA therapeutically, carbapenems lower VPA concentrations abruptly, dramatically, and for a sustained period. This article discusses the possibility of exploiting this pharmacokinetic drug–drug interaction in patients with or at risk of severe VPA poisoning.