Valproic Acid and Aspirin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Valproic Acid
Aspirin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased valproic acid exposure
Interaction Deep Dive
Use caution while using aspirin and valproic acid concomitantly. During coadministration, aspirin can displace protein-bound valproic acid and may result in increased serum valproic acid levels12. Salicylates have been shown to alter both the metabolism and protein binding of valproic acid. This has resulted in increased free valproate free fractions 5 by 30% to 65% 67.
Why it happens (mechanism)
Displacement of valproic acid from plasma protein binding sites
Literature reports
2 reports — tap to read
a) Six epileptic children who were taking valproic acid received antipyretic doses of aspirin. The steady-state free fraction of valproate rose from 12% to 43% in the presence of salicylate in five of these patients. Half-life of valproate, based upon total and free valproate concentrations, increased. Renal excretion of unchanged valproate decreased with salicylates. Salicylates appear to displace valproate from serum protein binding sites and alter valproate metabolism 34.
b) A study involving the coadministration of aspirin at antipyretic doses (11 to 16 mg/kg) with valproate to six pediatric patients revealed a decrease in protein binding and an inhibition of metabolism of valproate. Valproate free fraction was increased 4-fold in the presence of aspirin compared to valproate alone. The beta-oxidation pathway consisting of 2-E-valproic acid, 3-OH valproic acid, and 3-keto valproic acid was decreased from 25% of total metabolites excreted on valproate alone to 8.3% in the presence of aspirin 2.
Common questions
Can I take Valproic Acid and Aspirin together?
Increased valproic acid exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Valproic Acid and Aspirin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Valproic Acid or Aspirin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Product Information: Depakote oral delayed-release tablets, divalproex sodium oral delayed-release tablets. AbbVie Inc (per manufacturer), North Chicago, IL, 2023. DailyMed
- Orr JM, Abbott FS, Farrell K, et al: Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects. Clin Pharmacol Ther 1982; 31:642-649. PubMed
- Farrell K, Orr JM, Abbott FS, et al: The effect of acetylsalicylic acid on serum free valproate concentrations and valproate clearance in children. J Pediatr 1982; 101:142-144. DOI
- Product Information: Depakote(R) ER, divalproex sodium extended-release tablets. Abbott Laboratories, North Chicago, IL, 2003. DailyMed
- Abbott FS, Kassam J, Orr JM, et al: The effect of aspirin on valproic acid metabolism. Clin Pharmacol Ther 1986; 40:94-100. PubMed
- Goulden KJ, Dooley JM, Camfield PR, et al: Clinical valproate toxicity induced by acetylsalicylic acid. Neurology 1987; 37:1392-1394. DOI
Keep reading about Valproic Acid
Keep reading about Aspirin
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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