Carbapenems and valproate: A consumptive relationship

Abstract

SummaryA 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.

S2k-Leitlinie: Status Epilepticus im Erwachsenenalter

“…Ferner ist zu beachten, dass es bei gleichzeitiger Gabe von Carbapenemen (z. B. Meropenem) oft nicht gelingt, einen ausreichenden Wirkspiegel aufzubauen [ 9 ].…”

Interventions of a clinical pharmacist in a medical intensive care unit – a retrospective analysis

“…For the daily review of the prescribed therapy for drugdrug interactions (DDIs), the CP used mainly Lexicomp ® interaction database and considered only clinically relevant interaction of type D (consider therapy modification) and type X (avoid combinations). For specific interactions, the CP studied in detail case-report and case-series reviews (e.g., fentanyl -linezolid interaction [18][19][20], esomeprazoleclopidogrel interaction [21][22][23][24][25], and carbapenem -valproate interaction [26][27][28][29][30]).…”

Prevention, Treatment, and Monitoring of Seizures in the Intensive Care Unit

“…One additional serious interaction to consider as the incidence of multidrug-resistant organisms increases is between carbapenem antibiotics and valproic acid. Numerous potential mechanisms exist to describe this interaction; however, it is believed that carbapanems inhibit an enzyme crucial to the production of the pharmacologically active moiety of valproic acid, resulting in significantly reduced plasma valproic acid concentrations [83,84,85]. In patients on valproic acid, alternatives to carbapenems should be utilized if possible.…”