Interaction between valproic acid and meropenem or ertapenem in patients with epilepsy: clinical relevance and results from pharmaceutical intervention.

Objective: The literature has described the interaction between valproic acid  and carbapenems. This interaction leads to decreases in plasma concentrations  of valproic acid. The main objectives of this study were  to assess its relevance in clinical practice, to identify variables associated with  increased seizure episode rates, and to analyse the impact of pharmaceutical intervention on avoiding the effects of this interaction.

Method: An observational retrospective study of inpatients with epilepsy  admitted between 2016 and 2020. Their pharmacological treatment throughout  admission was recorded, and the presence of other interactions  leading to decreased plasma concentrations of valproic acid was reviewed. The  seizure rate during the year prior to admission was compared to that during  the interaction period. For every episode in which the interaction was detected, an intervention was conducted by providing the prescriber with information on  the interaction and suggesting a change of antibiotherapy as well as the  pharmacokinetic monitoring of valproic acid.

Results: 37 episodes were included. 58.1% of the patients were male and  median age was 70 years. In total, 56.8% of the patients received meropenem  and 43.2% received ertapenem. The median duration of  concomitant treatment with valproic acid and carbapenem was 4 days. The  incidence rate ratio was 2.60 (95% confidence interval: 1.61-4.21). Thus, this  interaction was associated with a higher seizure rate. A statistically significant  association was found between higher seizure rates and patients treated with  more than one anti-epileptic drug. Hospital pharmacists detected 24 episodes  (64.9%). In total, 17 interventions (70.8%) were accepted and 13  combinations were discontinued. Pharmacokinetic monitoring was conducted in  13 episodes (35.1%) and infratherapeutic levels were found in all of them.

Conclusions: The interaction between valproic acid and meropenem or ertapenem is clinically relevant. It is recommended that this combination should be avoided provided that a viable alternative is available.  Pharmaceutical intervention may contribute to preventing seizures associated with this combination.