Drug Interaction Report

Valproic Acid and Felbamate: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Felbamate

Felbatol Felbatol®
+

Valproic Acid

Depakene® Depakote® Depakote® ER Depakote® Sprinkle
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 35 documented Valproic Acid interactions, 26 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
delayed
Evidence
probable
Severity
Major

What happens

Increased valproic acid exposure

Interaction Deep Dive

Coadministration of felbamate (1200 mg to 2400 mg daily) and valproic acid resulted in an increase in mean valproic acid AUC (28% and 54%), peak concentrations (34% and 55%), and average steady-state concentrations (28% and 54%)23. Coadministration of 1200 mg/day of felbamate with valproate to patients with epilepsy (n=10) revealed an increase in mean valproate peak concentration by 35% (from 86 to 115 mcg/mL) compared to valproate alone. Increasing the felbamate dose to 2400 mg/day increased the mean valproate peak concentration to 133 mcg/mL (another 16% increase). A decrease in valproate dosage may be necessary when felbamate therapy is initiated 1.

Why it happens (mechanism)

Decreased valproic acid clearance

Literature reports

2 reports — tap to read

a) A study involving the coadministration of 1200 mg/day of felbamate with valproate to patients with epilepsy (n=10) revealed an increase in mean valproate peak concentration by 35% (from 86 to 115 mcg/mL) compared to valproate alone. Increasing the felbamate dose to 2400 mg/day increased the mean valproate peak concentration to 133 mcg/mL (another 16% increase) 1.

b) Coadministration of felbamate (1200 mg to 2400 mg daily) and valproic acid resulted in an increase in mean valproic acid AUC (28% and 54%), peak concentrations (34% and 55%), and average steady-state concentrations (28% and 54%) 2.

Common questions

Can I take Valproic Acid and Felbamate together?

Increased valproic acid exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Valproic Acid and Felbamate 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 Felbamate 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 (3)

  1. Product Information: Depakote oral delayed-release tablets, divalproex sodium oral delayed-release tablets. AbbVie Inc (per manufacturer), North Chicago, IL, 2023. DailyMed
  2. Wagner ML, Graves NM, Leppik IE, et al: The effect of felbamate on valproic acid disposition (abstract). Pharmacotherapy 1992; 12:260. PubMed
  3. Product Information: Felbatol(R), felbamate. Wallace Laboratories, Cranbury, NJ, 2000. DailyMed
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Beyond drug–drug

These medications also interact with supplements

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.