Clinical valproate toxicity induced by acetylsalicylic acid

We report three patients with serious clinical valproate (VPA) toxicity induced by interaction with acetylsalicylic acid (ASA). Two patients had a documented rise in VPA free level, and the third showed only clinical signs of toxicity. Symptoms resolved in all three when the ASA was stopped. This interaction has been previously documented under experimental conditions, and is due to displacement of VPA from plasma protein binding sites and a probable interference in metabolism. This is the first report of the clinical significance of this interaction.