First case report of suspected onset of convulsive seizures due to co-administration of valproic acid and tebipenem.

Objective: A patient presented with convulsive seizures when sodium valproate (VPA) and tebipenem pivoxil (Orapenem) were co-administered accidentally. The seizures were suspected to be caused by a reduced concentration of VPA in the blood.

Case Summary: A 6-year-old boy (weight: 16 kg, at the start of treatment) began sodium valproate (valproate syrup 5%) treatment for epilepsy in February 2012. At a dose of 350 mg/day, he experienced no convulsive seizures and maintained stable symptoms for the past 9 months. In December, he was prescribed 160 mg/day tebipenem pivoxil by an otolaryngologist for inflammation of the tympanic membrane. He experienced convulsive seizures the day after beginning co-administration. The concentration of VPA in his blood at this time was 30.0 μg/mL, which was lower than the optimal blood concentration.

Discussion: Marked reduction of VPA concentration in the blood due to co-administration of VPA and injectable carbapenem antibiotics has been well-documented; however, this is the first report of such an interaction with tebipenem, which is an orally-administered carbapenem antibiotic. Although the mechanism of drug interaction between VPA and carbapenem antibiotics is not fully understood, it is thought that VPA blood concentrations decrease due to production of valproic acid glucuronic acid conjugates (VPA-Gluc) being promoted directly or indirectly by carbapenem antibiotics. When we assessed the patient according to the DIPS system, we calculated a score of +4 (possibility of interaction).

Conclusions: The results suggest that co-administration of oral carbapenem antibiotics and VPA should be avoided.