Vanishing valproate: significant reductions in serum levels of valproate with meropenem coadministration

Background: The first report of a valproate-meropenem interaction was published in 1998 and a warning was issued by the US Food and Drug Administration in 2001. Despite the documentation of this clinically significant drug interaction, there may be limited awareness among clinicians in Australia. Clinical Details: We report a case of a patient stabilised on valproate and topiramate for epilepsy who was started on intravenous meropenem for neutropenic sepsis. Within 48 hours of starting meropenem, the patient experienced multiple tonic- clonic seizures and the trough serum valproate concentration was 161 micromol/L. 2 weeks prior to meropenem initiation, a trough serum valproate concentration was 672 micromol/L. Our patient experienced a 75 reduction in serum valproate concentration within 48 hours of starting meropenem. Conclusion: Co-administration of valproate and meropenem should be avoided due to the rapid onset and extent of the interaction.