Drug Interaction Report

Midostaurin and Rilzabrutinib: Interaction Details

A pharmacist-reviewed analysis of the Midostaurin 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
+

Midostaurin

Rydapt Rydapt®
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
Moderate
Can be significant — usually manageable with 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 133 documented Midostaurin interactions, 6 are rated moderate — including this one.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions

Interaction Deep Dive

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 accordingly. 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 daily1.

Why it happens (mechanism)

Inhibition of CYP3A-substrate metabolism by rilzabrutinib

Literature reports

1 report — tap to read

a) 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 Midostaurin and Rilzabrutinib together?

Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Midostaurin and Rilzabrutinib interaction?

It is rated moderate. Can be significant — usually manageable with 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 Midostaurin 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 anything you'd monitor while I'm on both?

References (1)

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

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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:

Midostaurin + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 130 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.