Carbapenems and valproate: A consumptive relationship

Abstract

A clinical case series is presented to characterize the interaction between carbapenem antibiotics and sodium valproate. Six illustrative cases are presented in which carbapenem therapy led to the rapid depletion of serum valproate levels, and one case is presented to demonstrate the difficulty of initiating valproate therapy in patients already on meropenem. The speed of valproate depletion after the initiation of carbapenem therapy, the effect of treatment duration, clinical manifestations, delay in valproate level normalization after carbapenem therapy, the efficacy of supplemental valproate doses, and the usefulness of valproate dose escalation are evaluated. Five out of the 7 patients became acutely symptomatic owing to their subtherapeutic valproate levels. The presented cases also highlight the relatively slow normalization of valproate levels after discontinuation of the antibiotic therapy. Our cases suggest that the interaction is not absorption-mediated because all of our patients received intravenous valproate. We observed that the introduction of alternative antiepileptic drugs (AEDs) may be preferable to valproate dose escalation, which is ineffective in the presence of concomitant meropenem therapy. The characterization and recognition of this interaction have implications for the management of a particularly vulnerable patient cohort.