Drug Interaction Report

Mitapivat and Zanubrutinib: Interaction Details

A pharmacist-reviewed analysis of the Mitapivat and Zanubrutinib 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

Zanubrutinib

Brukinsa Brukinsa®
+

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 zanubrutinib exposure and reduced efficacy of zanubrutinib

Interaction Deep Dive

Avoid concomitant use of zanubrutinib (a CYP3A substrate) and mitapivat (a moderate CYP3A inducer) as it may reduce zanubrutinib exposure, which may reduce zanubrutinib efficacy. If these inducers cannot be avoided, increase zanubrutinib dosage to 320 mg twice daily2. Monitor for loss of therapeutic effect 1. After discontinuation of mitapivat, resume previous dose of zanubrutinib 2.

Why it happens (mechanism)

Induction of CYP3A-mediated metabolism of zanubrutinib

Literature reports

2 reports — tap to read

a) Coadministration of mitapivat with midazolam (a sensitive CYP3A substrate) decreased midazolam AUC (infinity) 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 1.

b) In drug interaction studies, coadministration of multiple doses of rifabutin (moderate CYP3A inducer) decreased the zanubrutinib Cmax by 48% and AUC by 44%. Coadministration of multiple doses of efavirenz (moderate CYP3A inducer) is predicted to decrease zanubrutinib Cmax by 58% and AUC by 60% 2.

Common questions

Can I take Mitapivat and Zanubrutinib together?

Reduced zanubrutinib exposure and reduced efficacy of zanubrutinib Always confirm with your pharmacist or prescriber before making any change.

How serious is the Mitapivat and Zanubrutinib 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 Zanubrutinib 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: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2022. DailyMed
  2. Product Information: BRUKINSA(R) oral capsules, oral tablets, zanubrutinib oral capsules, oral tablets. BeOne Medicines USA, Inc. (per FDA), Pennington, NJ, 2025. DailyMed
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Zanubrutinib

Keep reading about Zanubrutinib

All Zanubrutinib interactions (52) Zanubrutinib drug information
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Mitapivat

Keep reading about Mitapivat

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

Zanubrutinib + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 152 more
Mitapivat + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 146 more

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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.