Abemaciclib and Rilzabrutinib: 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
Rilzabrutinib
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.
Here's what's going on. Your cancer medicine, abemaciclib (Verzenio), is broken down by a liver enzyme called CYP3A. Rilzabrutinib (Wayrilz) slows that enzyme down. When the enzyme works slower, abemaciclib can build up in your body a bit more than usual.
That means you could notice more of abemaciclib's usual side effects, like diarrhea, tiredness, or low blood counts. This is expected based on how the drugs work, not from lots of real-world reports. The good news: your care team can manage this by watching you a little more closely and adjusting your dose if needed. Please don't change anything on your own, just check in with your doctor or pharmacist.
Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor; abemaciclib is a CYP3A substrate (not a prodrug). Inhibition reduces abemaciclib clearance, increasing its exposure and adverse-reaction risk.
Direction/magnitude: Increased abemaciclib AUC/Cmax expected. Benchmark: rilzabrutinib raised midazolam Cmax and AUC 2.2-fold (single dose), with up to 3.0-fold AUC predicted at 400 mg BID.
Evidence: Theoretical for this pair. Onset: unspecified.
- Monitor for abemaciclib toxicity: diarrhea, neutropenia, hepatotoxicity, fatigue, VTE signs.
- Consider abemaciclib dose reduction per label CYP3A-inhibitor guidance, individualized by the team.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
When rilzabrutinib, a moderate inhibitor of CYP3A, is given together with substrates of CYP3A, exposure to those substrates may rise, thereby heightening the likelihood of adverse reactions linked to them. Watch more closely for adverse reactions to the co-administered CYP3A substrate and consider adjusting its dosage as needed. In a drug interaction study conducted in healthy participants, taking a single 400 mg dose of rilzabrutinib alongside midazolam (a sensitive CYP3A substrate) raised the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise by as much as 3.0-fold when co-administered with rilzabrutinib 400 mg twice daily1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by rilzabrutinib
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is manageable.
- Your team may monitor you more closely for abemaciclib side effects such as diarrhea, unusual tiredness, signs of infection, or liver problems.
- Your abemaciclib dose may be adjusted and individualized by your oncology team while you are on rilzabrutinib.
- Report new or worsening diarrhea, fever, or fatigue promptly.
Before starting or stopping either drug, or any new medicine, check with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study conducted in healthy volunteers, administering a single 400 mg dose of rilzabrutinib together with midazolam (a sensitive CYP3A substrate) raised the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, the midazolam AUC is projected to rise as much as 3.0-fold when combined with 400 mg rilzabrutinib administered twice daily 1.
Common questions
Can I take Abemaciclib and Rilzabrutinib together?
Rilzabrutinib can raise abemaciclib levels and side effects by slowing its breakdown, so your care team may watch you more closely and adjust the abemaciclib dose. Keep taking both as prescribed and report new diarrhea, fever, or fatigue. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib 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 is the Abemaciclib and Rilzabrutinib interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is manageable. Your team may monitor you more closely for abemaciclib side effects such as diarrhea, unusual tiredness, signs of infection, or liver problems. Your abemaciclib dose may be adjusted and individualized by your oncology team while you are on rilzabrutinib. Report new or worsening diarr… Management is individual — always follow your own care team's guidance.
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 Abemaciclib 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)
- Product Information: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
Keep reading about Rilzabrutinib
Keep reading about Abemaciclib
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