Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem

Abstract

This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

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

“…doripenem (Hellwig et al, 2011), ertapenem (Lunde et al, 2007), and meropenem (Llinares Tello et al, 2003;Coves-Orts et al, 2005;Fudio et al, 2006;Taha et al, 2013) with VPA is associated with a clinically significant decrease in the plasma concentrations of VPA. A series of 26 patients with concomitant meropenem and VPA treatment supports the findings of these cases (Vélez Díaz-Pallarés et al, 2012).…”

“…The effects of carbapenems on VPA concentrations seem to indicate a class effect (Mancl and Gidal, 2009), and the magnitude of the effects seem to be equal among various carbapenems; the decrease in VPA concentrations has been in the range of 50 to 96% (Llinares Tello et al, 2003;Coves-Orts et al, 2005;Hellwig et al, 2011;Lunde et al, 2007;Park et al, 2012;Taha et al, 2013;Perea et al, 2006;Vélez Díaz-Pallarés et al, 2012). The interaction has been observed when VPA has been administered either enterally (Park et al, 2002;Llinares Tello et al, 2003;Fudio et al, 2006;Taha et al, 2013) or intravenously (Coves-Orts et al, 2005;Lunde et al, 2007;Hellwig et al, 2011). As with our patient, the reported decrease in the plasma concentrations of VPA due to the interaction has often been associated with an exacerbation of seizures (Coves-Orts et al, 2005;Fudio et al, 2006;Lunde et al, 2007;Taha et al, 2013).…”

“…VPA has clinically significant drug interactions, most commonly with other AEDs. However, several case reports suggest that some carbapenems, administered concomitantly with VPA, cause a dramatic decrease in the plasma concentrations of VPA with a risk of exacerbation of seizures (Llinares Tello et al, 2003;Coves-Orts et al, 2005;Fudio et al, 2006;Lunde et al, 2007;Hellwig et al, 2011;Taha et al, 2013).…”

Valproic Acid-Carbapenem Interaction: Report of Six Cases and a Review of the Literature

“…Within 24 hours after initiating carbapenem treatment, decreased plasma concentrations of VPA have been found in all patients reported to date who have had VPA levels measured at this time 716,21,297, including 19 (100%) of 19 patients who received daily VPA monitoring in the large case series described recently by Spriet et al 7317. In contrast to treatment with carbapenem antibiotics alone, in which the average onset of the uncommon occurrence of seizure activity is 7 days 71057, seizures, which are often the first sign of an interaction, may occur in less than 24 hours 7257 and frequently within 48 hours after addition of carbapenem therapy to VPA treatment 714, 15,22,23,327. Along with information suggesting that the VPAcarbapenem interaction may result in changes in tissue levels and/or pharmacological activity of VPA that are discordant or disproportionately decreased in comparison with concurrent plasma concentrations, these characteristics indicate that therapeutic drug monitoring of VPA in these situations may be misleading and potentially capable of providing a false sense of security.…”

Characterization of Inhibitory Effect of Carbapenem Antibiotics on the Deconjugation of Valproic Acid Glucuronide

“…However, most of the previously proposed mechanisms (mechanisms 1-5) may not solely explain the interaction observed under clinical conditions for the following reasons: with mechanism 1, the interaction observed after intravenous administration of VPA (Clause et al, 2005;Coves-Orts et al, 2005;Spriet et al, 2007) cannot be accounted for. For mechanism 2, the interaction in bile duct-cannulated rats, in which enterohepatic circulation of VPA was negligible (Yamamura et al, 1999), cannot be accounted for.…”