Abemaciclib and Repotrectinib: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Abemaciclib
Repotrectinib
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.
Let's talk about taking Verzenio (abemaciclib) with Augtyro (repotrectinib) together. Your cancer medicine abemaciclib is broken down by a liver enzyme called CYP3A4. Repotrectinib speeds that enzyme up, so your body may clear the abemaciclib faster than it should. That means there could be less abemaciclib in your system, and it may not work as well against your cancer.
The good news is your care team can manage this. They may adjust your abemaciclib dose or watch you more closely. Please keep taking both exactly as prescribed, and talk with your oncologist or pharmacist before changing anything.
Effect: Repotrectinib induces CYP3A4, reducing exposure of CYP3A4 substrates. Abemaciclib is a CYP3A4 substrate, so co-administration is expected to decrease abemaciclib AUC/Cmax and potentially reduce antitumor efficacy.
- Direction: Reduced abemaciclib exposure (enzyme induction, not a prodrug).
- Magnitude: Index substrate midazolam showed AUC decreased 69%, Cmax 48% with repotrectinib.
- Evidence: Probable. Severity: Major. Onset: Unspecified (induction is typically delayed).
- Management: Avoid concomitant use where feasible. If unavoidable, the abemaciclib dose may need to be increased and individualized, with closer monitoring of response.
What happens
Reduced CYP3A4 substrates exposure and reduced efficacy of CYP3A4 substrates
Interaction Deep Dive
Concurrent administration of repotrectinib with CYP3A4 substrates that have a narrow therapeutic index should be avoided, since repotrectinib acts as a CYP3A4 inducer. When taken together, repotrectinib lowers the exposure of CYP3A4 substrates, and even small changes in concentration may result in diminished efficacy. Should co-administration be unavoidable, raise the dose of the CYP3A4 substrate as needed. Drug interaction studies showed that midazolam (a CYP3A4 substrate) had its AUC (0 to inf) fall by 69% and its Cmax fall by 48% when given together in subjects who had previously received 160 mg of repotrectinib once daily for 14 days and then 160 mg twice daily for 7 days1.
Why it happens (mechanism)
Induction of CYP3A4-substrate metabolism by repotrectinib
How to manage this interaction
Here is how a care team typically handles this combination:
- Avoid when possible: Your oncologist may prefer not to use these two together, especially given the risk of reduced abemaciclib effect.
- Dose adjustment: If both are needed, your abemaciclib dose may need to be increased and individualized by your care team.
- Closer monitoring: Your team may watch your response more closely.
Keep taking both medicines exactly as prescribed. Do not change doses on your own. Raise this combination with your pharmacist or oncologist so they can confirm the best plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In the drug interaction studies, following concurrent administration in subjects who had previously received 160 mg repotrectinib once daily for 14 days and then 160 mg twice daily for 7 days, the AUC (0 to inf) of midazolam (a CYP3A4 substrate) fell by 69% and the Cmax by 48% 1.
Common questions
Can I take Abemaciclib and Repotrectinib together?
Repotrectinib can lower abemaciclib levels and make it work less well; keep taking both as prescribed and ask your oncologist whether the dose should be adjusted or the combination avoided. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Repotrectinib 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 is the Abemaciclib and Repotrectinib interaction managed?
Here is how a care team typically handles this combination: Avoid when possible: Your oncologist may prefer not to use these two together, especially given the risk of reduced abemaciclib effect. Dose adjustment: If both are needed, your abemaciclib dose may need to be increased and individualized by your care team. Closer monitoring: Your team may watch your response more closely. Keep taking bot… Management is individual — always follow your own care team's guidance.
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 Abemaciclib or Repotrectinib 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: AUGTYRO(TM) oral capsules, repotrectinib oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Abemaciclib
Keep reading about Repotrectinib
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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