Meropenem and Valproic Acid Interaction: A Systematic Review of Case Reports and Case Series

Background: This systematic review focused on the evidence regarding meropenem (MRP) and valproic acid (VPA) interaction. Method: the electronic databases consulted were PubMed, Scopus, and EBSCO, searching for cases reported related to the interaction between 1998 and 2018. Results: 35 articles were selected for this work from a total of 162 articles found in the databases, 10 selected for qualitative analysis, and 25 for quantitative analysis, with a total of 55 cases. It has been observed that: a) the VPA blood levels significantly decreased by 75-90% from the initial values (reference range 50-100 mcg/ml) 24 hours after the MRP administration; b) although VPA doses were increased, no consistent augmentation in VPA blood concentration was achieved; c) the interaction was independent of the age group; d) the VPA levels recovery could have started (between 1 and 20 days) after the MRP withdrawal. Conclusion: This systematic review proposes that the level of evidence corresponds to 3 with recommendation D level according to SING. This work has demonstrated robust evidence because of the high number and quality of cases reported. Here, the interaction was qualified as probable due to the MRP's re-entry according to the data.