Drug Interaction Report

Midostaurin and Phenytoin: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Phenytoin

Dilantin Phenytek
+

Midostaurin

Rydapt Rydapt®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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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 133 documented Midostaurin interactions, 116 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

Decreased midostaurin exposure

Interaction Deep Dive

Concomitant use of midostaurin with a strong CYP3A inducer may decrease exposure to midostaurin and reduce efficacy. Midostaurin AUC was decreased by 96% when coadministered with rifampin and AUC of the active metabolites was also decreased. Avoid coadministration of midostaurin with a strong CYP3A inducer1.

Why it happens (mechanism)

Induction of CYP3A4-mediated midostaurin metabolism

Literature reports

1 report — tap to read

a) AUC(infinity) levels of midostaurin and the active metabolite CGP62221 were decreased by 96% and 92%, and AUC(0 to tau) of the active CGP52421 metabolite was decreased by 59%, when the strong CYP3A4 inducer rifampin 600 mg/day for days 1 to 14 was coadministered on day 9 with a single 50-mg dose of midostaurin 1.

Common questions

Can I take Midostaurin and Phenytoin together?

Decreased midostaurin exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Midostaurin and Phenytoin 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 Midostaurin or Phenytoin 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: RYDAPT(R) oral capsules, midostaurin oral capsules. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2017. DailyMed
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Beyond drug–drug

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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.