Drug Interaction Report

Mitapivat and Rilzabrutinib: Interaction Details

A pharmacist-reviewed analysis of the Mitapivat and Rilzabrutinib 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

Rilzabrutinib

Wayrilz
+

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 rilzabrutinib exposure, reduced efficacy of rilzabrutinib, increased CYP3A substrate exposure and an increased risk of CYP3A4 substrate-related adverse reactions

Interaction Deep Dive

Avoid concomitant use of rilzabrutinib (CYP3A substrate) with moderate CYP3A inducers as it may reduce rilzabrutinib exposure, which may reduce rilzabrutinib efficacy. Additionally, coadministration of rilzabrutinib (moderate CYP3A inhibitor) and CYP3A substrates may increase CYP3A substrates exposure, which increases the risk of adverse reactions related to these substrates. Monitor for adverse reactions of the concurrently administered CYP3A substrate more frequently and consider dosage adjustment accordingly1.

Why it happens (mechanism)

Induction of CYP3A4-mediated metabolism of rilzabrutinib; inhibition of CYP3A-substrate metabolism by rilzabrutinib

Literature reports

2 reports — tap to read

a) In a drug interaction study, coadministration of moderate CYP3A inducers (efavirenz, rifabutin) is predicted to reduce rilzabrutinib Cmax and AUC by up to 70% at steady state 1.

b) In a drug interaction study with healthy participants, concomitant use of a single dose of rilzabrutinib 400 mg with midazolam (sensitive CYP3A substrate) increased midazolam Cmax and AUC by 2.2-fold. Midazolam AUC is predicted to increase up to 3.0-fold in patients with immune thrombocytopenia following coadministration with 400 mg rilzabrutinib twice daily 1.

Common questions

Can I take Mitapivat and Rilzabrutinib together?

Reduced rilzabrutinib exposure, reduced efficacy of rilzabrutinib, increased CYP3A substrate exposure and an increased risk of CYP3A4 substrate-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Mitapivat and Rilzabrutinib 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 Rilzabrutinib 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 (1)

  1. Product Information: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
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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:

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.