Abemaciclib and Fedratinib: 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
Fedratinib
Abemaciclib
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.
These two cancer medicines can interact. Fedratinib (Inrebic) slows down a liver enzyme called CYP3A4, which is the same enzyme your body uses to break down abemaciclib (Verzenio). When that enzyme is blocked, abemaciclib can build up to higher levels than usual.
Higher abemaciclib levels can mean more side effects, like diarrhea, low blood counts, or fatigue. The good news is this is very manageable. Your cancer team can watch you more closely and adjust your abemaciclib dose if needed. Please don't stop or change either medicine on your own, just talk with your oncologist or pharmacist so they can tailor things for you.
Effect: Increased abemaciclib exposure. Fedratinib is a moderate CYP3A4 inhibitor; abemaciclib is a CYP3A4 substrate (and active-metabolite parent), so inhibition raises abemaciclib AUC/Cmax and adverse-reaction risk.
- Direction: Increased substrate (abemaciclib) exposure.
- Magnitude: Not established for this pair; fedratinib increased midazolam AUC ~4-fold.
- Onset: Unspecified.
- Evidence: Probable.
- Management: Monitor for abemaciclib toxicity (diarrhea, neutropenia, hepatotoxicity, fatigue). Consider abemaciclib dose reduction per label guidance for concomitant CYP3A inhibitors; individualize and monitor CBC and LFTs.
What happens
Increased CYP3A4 substrate exposure
Interaction Deep Dive
Taking fedratinib, which inhibits CYP3A4, alongside drugs metabolized by CYP3A4 can raise the levels of those substrates and heighten the potential for adverse reactions related to them. Single-dose pharmacokinetic investigations showed that fedratinib produced a 4-fold rise in the AUC of midazolam (a CYP3A4 substrate). When the two must be given together, watch for adverse reactions and modify the dose of any CYP3A4 substrate accordingly1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated substrate metabolism by fedratinib
How to manage this interaction
If your care team prescribes both, they can manage this safely.
- Keep taking both as prescribed unless your oncologist tells you otherwise.
- Your abemaciclib dose may be adjusted and individualized by your team because fedratinib can raise its levels.
- Expect closer monitoring for side effects, which may include blood tests to check your blood counts and liver.
- Report new or worsening diarrhea, extreme tiredness, signs of infection, or yellowing of the skin or eyes promptly.
Ask your pharmacist or prescriber before starting, stopping, or changing either medicine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When a single 2 mg dose of midazolam (a CYP3A4 substrate) was given together with fedratinib, the AUC of midazolam rose by 4-fold 1.
Common questions
Can I take Abemaciclib and Fedratinib together?
Fedratinib can raise abemaciclib levels by blocking CYP3A4, increasing side-effect risk, so your team may lower the abemaciclib dose and watch you more closely. Don't change either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Fedratinib 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 Fedratinib interaction managed?
If your care team prescribes both, they can manage this safely. Keep taking both as prescribed unless your oncologist tells you otherwise. Your abemaciclib dose may be adjusted and individualized by your team because fedratinib can raise its levels. Expect closer monitoring for side effects, which may include blood tests to check your blood counts and liver. Report new or worsening diarrhea, extre… 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 Fedratinib 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: INREBIC(R) oral capsules, fedratinib oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Fedratinib
Keep reading about Abemaciclib
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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