Carbapenems: concomitant use with valproic acid not recommended

A clinically significant interaction between carbapenems and valproic acid results in reduced valproate plasma concentrations with potential for inadequate seizure control. Concomitant use of these agents is not recommended, and healthcare professionals should consider alternative antibacterial therapy

Article date: May 2010

Carbapenems are a class of beta-lactam antibiotics with broad-spectrum antibacterial activity.

They are indicated for the treatment of the following infections when caused by susceptible bacteria:

  • nosocomial pneumonia
  • complicated intra-abdominal infections
  • complicated urinary tract infections

Valproic acid/sodium valproate is an anticonvulsant used for the treatment of generalised, partial, or other epilepsy.

Four carbapenems are authorised in the UK which includes:

  • doripenem (Doribax▼)
  • ertapenem (Invanz▼)
  • imipenem-cilastatin (Primaxin)
  • meropenem (Meronem)

Full details are available in the Summaries of Product Characteristics.

An interaction between carbapenems and valproic acid has been described in a number of case reports and one identified study.1 The mechanism of the interaction has not been elucidated; however, several potential mechanisms have been proposed in the literature. 2

A more-recent unpublished pharmacokinetic study of 24 healthy human volunteers found that concomitant administration of valproic acid and doripenem resulted in a rapid and substantial fall in plasma valproate levels. Given the large magnitude and rapid time course of this interaction, monitoring of sodium valproate levels or making dose adjustments are unlikely to manage this interaction, which could lead to inadequate seizure control.

A Europe-wide class review of data for the remaining carbapenems found that decreased valproic acid levels have also been reported when co-administered with other carbapenems, with 60–100% decreases in valproic acid levels being observed within about 2 days. This interaction is therefore likely to be a class effect. Concomitant use of carbapenems and valproic acid/sodium valproate is not recommended, and prescribers should consider alternative antibacterial therapy.

Advice for healthcare professionals:

  • a clinically significant interaction between carbapenems and valproic acid/sodium valproate results in reduced valproate plasma concentrations with potential for inadequate seizure control
  • given the large magnitude and rapid time course of this interaction, monitoring of sodium valproate levels or making dose adjustments are unlikely to manage this interaction
  • concomitant use of carbapenems in patients taking valproic acid/sodium valproate is not recommended and prescribers should consider alternative antibacterial therapy

For further information see the monthly report from the EU Pharmacovigilance Working Party

Article citation: Drug Safety Update May 2010, vol 3 issue 10: 4.

  1. Spriet I, et al. Ann Pharmacother 2007; 41: 1130–36.

  2. Mori H, et al. Drug Metab Rev 2007; 39: 647–57.

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