Abemaciclib and Adagrasib: 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
Adagrasib
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 are both cancer medicines. Adagrasib (Krazati) slows down a liver enzyme called CYP3A4 that your body uses to break down abemaciclib (Verzenio). When that enzyme is slowed, abemaciclib can build up to higher levels than intended.
Higher levels can mean more side effects, like diarrhea, low blood counts, or feeling very tired. The good news is your cancer team knows about this and can manage it. Please don't stop or change either medicine on your own. Just talk with your oncologist or pharmacist so they can decide the safest plan for you.
Effect: Adagrasib is a strong CYP3A4 inhibitor; abemaciclib is a CYP3A4 substrate. Co-administration inhibits abemaciclib metabolism, increasing its exposure (AUC/Cmax) and the risk of dose-dependent toxicity.
- Direction: Increased abemaciclib effect/toxicity.
- Magnitude: Not directly quantified for abemaciclib; adagrasib raised midazolam AUC ~4.8-fold and Cmax ~21-fold, indicating potent inhibition.
- Evidence: Probable. Onset: Unspecified.
- Management: Avoid concomitant use where possible. If unavoidable, dose reduction and closer monitoring for abemaciclib toxicity (diarrhea, neutropenia, hepatotoxicity, fatigue) per specialist guidance.
What happens
Increased CYP3A4 substrate exposure
Interaction Deep Dive
Do not use adagrasib together with sensitive CYP3A4 substrates, because doing so can raise the exposure of those substrates and thereby heighten the likelihood of adverse reactions associated with them. In one study, giving adagrasib at 400 mg twice daily alongside midazolam (a sensitive CYP3A4 substrate) produced a 4.8-fold rise in midazolam AUC and a 21-fold rise in its Cmax. At the 600 mg twice daily dose of adagrasib, midazolam AUC and Cmax are predicted to increase by 3.1-fold and 31-fold, respectively1.
Why it happens (mechanism)
Inhibition of CYP3A4 substrate metabolism by adagrasib
How to manage this interaction
Your care team is well equipped to handle this combination.
- Because adagrasib can raise abemaciclib levels, your team may avoid using them together when possible, or choose an alternative.
- If both are needed, your abemaciclib dose may need to be adjusted and individualized, and your team may monitor you more closely for side effects.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Report new or worsening diarrhea, unusual tiredness, signs of infection, or yellowing of the skin/eyes to your oncologist or pharmacist promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Taking adagrasib at a dose of 400 mg twice daily together with midazolam (a sensitive CYP3A4 substrate) raised midazolam's AUC by 4.8-fold and its Cmax by 21-fold. At a 600 mg twice daily dose of midazolam, the projected rise in midazolam AUC and Cmax is 3.1-fold and 31-fold respectively 1.
Common questions
Can I take Abemaciclib and Adagrasib together?
Adagrasib strongly blocks the enzyme that clears abemaciclib, so abemaciclib can build up and cause more side effects; your care team will usually avoid the combination or lower the dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Adagrasib 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 Adagrasib interaction managed?
Your care team is well equipped to handle this combination. Because adagrasib can raise abemaciclib levels, your team may avoid using them together when possible, or choose an alternative. If both are needed, your abemaciclib dose may need to be adjusted and individualized, and your team may monitor you more closely for side effects. Keep taking both exactly as prescribed unless your prescriber te… 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 Adagrasib 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: KRAZATI(TM) oral tablets, adagrasib oral tablets. Mirati Therapeutics Inc (per FDA), San Diego, CA, 2024. DailyMed
Keep reading about Adagrasib
Keep reading about Abemaciclib
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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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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