Drug Interaction Report

Mitapivat and Phenytoin: Interaction Details

A pharmacist-reviewed analysis of the Mitapivat and Phenytoin interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Phenytoin

Dilantin Phenytek
+

Mitapivat

Aqvesme Pyrukynd Pyrukynd®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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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 295 documented Mitapivat interactions, 262 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
unspecified
Evidence
theoretical
Severity
Major

What happens

Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure, reduced mitapivat exposure and reduced efficacy of mitapivat

Interaction Deep Dive

Avoid coadministration of mitapivat and phenytoin or fosphenytoin (prodrug of phenytoin) (strong CYP3A inducer that is sensitive CYP2C9/CYP2C19 substrate with NTI) as concomitant use reduces both mitapivat and phenytoin or fosphenytoin exposure, which reduces efficacy21. If coadministration is required, monitor for loss of therapeutic effect 2.

Why it happens (mechanism)

Induction of CYP3A-mediated metabolism of phenytoin or fosphenytoin (prodrug of phenytoin); induction of CYP2C9-mediated metabolism of mitapivat; induction of CYP2C19-mediated metabolism of mitapivat

Literature reports

1 report — tap to read

a) Coadministration of mitapivat with rifAMPin, a strong CYP3A inducer, decreased mitapivat AUC(infinity) and Cmax by 91% and 77%, respectively, following a single dose of mitapivat 50 mg. Additionally, rifAMPin decreased mitapivat AUC(0 to 12) and Cmax by approximately 95% and 85%, respectively, following administration of mitapivat 5, 20 or 50 mg twice daily 21.

Common questions

Can I take Mitapivat and Phenytoin together?

Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure, reduced mitapivat exposure and reduced efficacy of mitapivat Always confirm with your pharmacist or prescriber before making any change.

How serious is the Mitapivat and Phenytoin interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Mitapivat or Phenytoin 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 (2)

  1. Product Information: AQVESME™ oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
  2. Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
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Phenytoin

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Mitapivat

Keep reading about Mitapivat

All Mitapivat interactions (295) Mitapivat drug information
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Phenytoin + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Kava L-tryptophan Siberian Cocklebur St. John's Wort + 216 more
Mitapivat + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 146 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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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.