Dihydroergotamine and Mitapivat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mitapivat
Dihydroergotamine
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
Reduced CYP3A substrate exposure
Interaction Deep Dive
Avoid concomitant use of mitapivat with sensitive CYP3A substrates with a narrow therapeutic index. Coadministration of mitapivat (a CYP3A inducer) with a sensitive CYP3A substrate reduces exposure of the sensitive CYP3A substrate1. If coadministration is required, monitor for loss of therapeutic effect . 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.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism by mitapivat
Literature reports
1 report — tap to read
a) 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 3. Similarly, midazolam AUC (inf) and Cmax decreased by 65% and 59%, respectively, with mitapivat 100 mg twice daily 1.
Common questions
Can I take Dihydroergotamine and Mitapivat together?
Reduced CYP3A substrate exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dihydroergotamine and Mitapivat 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Dihydroergotamine or Mitapivat 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)
- Product Information: AQVESME™ oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2022. DailyMed
- Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
Keep reading about Mitapivat
Keep reading about Dihydroergotamine
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