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Bayer Aspirin (with caffeine) oral

Valproic Acid/Salicylates

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not properly process valproic acid.

What might happen:

Your blood levels of valproic acid may increase and cause toxic effects.

What you should do about this interaction:

If you experience loss of coordination, drowsiness, tremor, or uncontrolled movements of your eyes, contact your healthcare professional (e.g. doctor or pharmacist). Your doctor may want to measure the amount of valproic acid in your blood and may adjust the dose.Your healthcare professionals may already be aware of this drug interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.


1.Orr JM, Abbott FS, Farrell K, Ferguson S, Sheppard I, Godolphin W. Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects. Clin Pharmacol Ther 1982 May; 31(5):642-9.
2.Abbott FS, Kassam J, Orr JM, Farrell K. The effect of aspirin on valproic acid metabolism. Clin Pharmacol Ther 1986 Jul;40(1):94-100.
3.Farrell K, Orr JM, Abbott FS, Ferguson S, Sheppard I, Godolphin W, Bruni J. The effect of acetylsalicylic acid on serum free valproate concentrations and valproate clearance in children. J Pediatr 1982 Jul; 101(1):142-4.
4.Schobben F, Vree TB, van der Kleijn E. Pharmacokinetics, metabolism and distribution of 2-N-propyl-pentanoate (sodium valproate) and the influence of salicylate comedication. In Meinardi, H. //Rowan, A. J. Advances in Epileptology Psychology, Pharmacotherapy and New Diagnostic Approaches. Amsterdam, Swets & Zeitlinger B. V. 1978;271-7.
5.Goulden KJ, Dooley JM, Camfield PR, Fraser AD. Clinical valproate toxicity induced by acetylsalicylic acid. Neurology 1987 Aug;37(8):1392-4.
6.Sandson NB, Marcucci C, Bourke DL, Smith-Lamacchia R. An interaction between aspirin and valproate: the relevance of plasma protein displacement drug-drug interactions. Am J Psychiatry 2006 Nov; 163(11):1891-6.
7.Addison RS, Parker-Scott SL, Eadie MJ, Hooper WD, Dickinson RG. Steady-state dispositions of valproate and diflunisal alone and coadministered to healthy volunteers. Eur J Clin Pharmacol 2000 Dec; 56(9-10):715-21.
8.Rettenmeier AW, Prickett KS, Gordon WP, Bjorge SM, Chang SL, Levy RH, Baillie TA. Studies on the biotransformation in the perfused rat liver of 2-n- propyl-4-pentenoic acid, a metabolite of the antiepileptic drug valproic acid. Evidence for the formation of chemically reactive intermediates. Drug Metab Dispos 1985 Jan-Feb;13(1):81-96.
9.Fleitman JS, Bruni J, Perrin JH, Wilder BJ. Albumin-binding interactions of sodium valproate. J Clin Pharmacol 1980 Aug-Sep;20(8-9):514-7.

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