Drug Interaction Report

Mitapivat and Repotrectinib: Interaction Details

A pharmacist-reviewed analysis of the Mitapivat and Repotrectinib 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

Mitapivat

Aqvesme Pyrukynd Pyrukynd®
+

Repotrectinib

Augtyro
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 repotrectinib exposure, reduced mitapivat exposure and reduced efficacy of mitapivat

Interaction Deep Dive

Avoid coadministration of mitapivat and repotrectinib (moderate CYP3A inducer that is sensitive CYP3A substrates with NTI) as concomitant use reduces both mitapivat and repotrectinib exposure, which reduces efficacy. Consider alternative therapy. If coadministration is required, monitor Hb and titrate beyond 50 mg twice daily if necessary2, but do not exceed 100 mg twice daily 21. If coadministration is required, monitor for loss of therapeutic effect 2.

Why it happens (mechanism)

Induction of CYP3A-mediated metabolism of repotrectinib; induction of CYP3A-mediated metabolism of mitapivat

Literature reports

2 reports — tap to read

a) Coadministration of mitapivat with efavirenz, a moderate CYP3A inducer, decreased mitapivat AUC (0 to 12) and Cmax by 60% and 30%, respectively, following mitapivat 5 or 20 mg twice daily. Additionally, efavirenz decreased mitapivat AUC (0 to 12) and Cmax by 55% and 24%, respectively, following administration of mitapivat 50 mg twice daily 2.

b) In drug interaction studies, coadministration of mitapivat with midazolam (a sensitive CYP3A substrate) decreased midazolam AUC(inf) and Cmax by 21% and 19% with mitapivat 5 mg twice daily, by 43% and 39% with mitapivat 20 mg twice daily, and by 57% and 52% with mitapivat 50 mg twice daily, respectively 2. Similarly, midazolam AUC (inf) and Cmax decreased by 65% and 59%, respectively, with mitapivat 100 mg twice daily 1.

Common questions

Can I take Mitapivat and Repotrectinib together?

Reduced repotrectinib 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 Repotrectinib 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 Repotrectinib 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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Mitapivat

Keep reading about Mitapivat

All Mitapivat interactions (295) Mitapivat drug information
Also serious with: Mavacamten Ranolazine Ensitrelvir Zoliflodacin
Repotrectinib

Keep reading about Repotrectinib

All Repotrectinib interactions (70)
Also serious with: Lefamulin Dofetilide Canagliflozin Olaparib
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:

Mitapivat + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 146 more
Repotrectinib + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Adrafinil + 178 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.