Midostaurin and Tucatinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tucatinib
Midostaurin
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
Increased exposure to CYP3A substrate and risk of toxicity
Interaction Deep Dive
Avoid concomitant use of tucatinib with a CYP3A substrate where minimal concentration changes may lead to serious or life-threatening toxicities. In a clinical study, concomitant use of tucatinib with midazolam (CYP3A substrate) significantly increased midazolam AUC and Cmax. If coadministration is required, reduce the CYP3A substrate dosage1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by tucatinib
Literature reports
1 report — tap to read
a) In a clinical study, coadministration of a single midazolam (CYP3A substrate with NTI) 2 mg dose with steady-state tucatinib 300 mg twice daily resulted in a ratio of midazolam exposure with and without tucatinib for AUC of 5.7 and Cmax of 3 1.
Common questions
Can I take Midostaurin and Tucatinib together?
Increased exposure to CYP3A substrate and risk of toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midostaurin and Tucatinib 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 Midostaurin or Tucatinib 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)
- Product Information: TUKYSA(TM) oral tablets, tucatinib oral tablets. Seattle Genetics Inc (per FDA), Bothell, WA, 2020. DailyMed
Keep reading about Tucatinib
Keep reading about Midostaurin
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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