Meropenem and Valproic Acid - A Combination with a High Risk of Severe Interaction

Carbapenems are frequently used last resort broad-spectrum antibiotics. Concomitant use of carbapenem and valproic acid (VPA) in intensive medicine is not infrequent. In this study, we focus on the interaction between meropenem and VPA since this antibiotic is used in the treatment of meningitis. A PubMed research with the search terms "meropenem" and "valproic acid" yielded 21 reports with 1 or 2 patients, with a total of 28 treatment episodes in 25 patients, and 9 case series with at least 3 cases each corresponding to 158 treatment episodes in 155 patients. In the case reports there was an average decrease in the levels of valproic acid by 66 % (SD 27 %) within the first 48 h after meropenem was administered. The maximum drop in levels was 84 % (SD 12 %). The maximal drop in levels of VPA in the case series in terms of the number of cases involved was 74.5 %. At least one-fourth of patients suffered epileptic attacks as a result of the concomitant use of these 2 drugs. Decrease in the levels of VPA was pronounced under the use of the meropenem and ertapenem. IV administration can weaken or delay the decrease in the levels of VPA, but the clinical relevance of this difference is questionable when meropenem or ertapenem is concomitantly applied. Maintenance of therapeutic levels of VPA under meropenem in particular may require daily doses for which there are no safety profile data. The concomitant administration of these 2 drugs should be avoided.