Concomitant treatment with imipenem causes a rapid and extensive decrease in the plasma concentrations of valproic acid

Abstract

Background. Valproic acid (VPA) is a wide-spectrum antiepileptic drug used both in children and in adults. We describe a clinically important interaction between VPA and imipenem, a carbapenem antimicrobial. Case presentation. Our patient was a 19-year-old man with childhood onset of mental retardation and severe epilepsy. He was hospitalized due to pneumonia. His antiepileptic drugs, including VPA, were administered intravenously. Due to pneumonia, intravenously administered imipenem was started. After the start of imipenem treatment, a dramatic decrease in the plasma concentrations of VPA occurred within 24 hours. After the discontinuation of imipenem treatment, the concentration of VPA recovered within a few hours. The decrease in VPA levels was associated with increased seizure frequency. Conclusions. The time course of the VPA-imipenem interaction suggests that mechanisms other than a change in the enzymatic elimination of VPA is the cause for this pharmacokinetic interaction. Concomitant use of VPA and imipenem should be avoided.

The role of the hepatic metabolisation for the interaction between valproic acid and carbapenem antibiotics

“…ear Sir, I read with great interest the paper by Keränen and Kuusisto (2016) reporting a rapid and substantial decrease in the plasma concentration of valproic acid (VPA) within 24 hours after beginning concomitant treatment with imipenem. When imipenem treatment was stopped four days later, the VPA plasma concentration increased within a few hours.…”