Abemaciclib and Sotorasib: 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
Sotorasib
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. Abemaciclib (Verzenio) is broken down in your body by an enzyme called CYP3A. Sotorasib (Lumakras) can speed up that enzyme, which means your body may clear the abemaciclib faster than it should. When that happens, the level of abemaciclib in your blood can drop, and it may not fight the cancer as well as it's meant to.
I want to be honest that this is based mostly on how these drugs behave in theory and in a related study, not on lots of direct data with this exact pair. Please don't change or stop either medicine on your own. Your cancer care team can manage this by adjusting your dose and watching you closely.
Effect: Sotorasib may induce CYP3A-mediated metabolism of abemaciclib (a CYP3A substrate), reducing abemaciclib exposure (AUC/Cmax) and risking therapeutic failure. Neither is relevant as a prodrug here; abemaciclib is the active affected agent.
- Direction: Reduced abemaciclib effect (enzyme induction).
- Magnitude: Not quantified for this pair; sotorasib significantly decreased midazolam exposure in a clinical study.
- Onset: Unspecified (induction typically develops over days).
- Evidence: Theoretical/extrapolated.
- Management: Avoid concomitant use where minimal concentration changes may cause failure. If required, increase abemaciclib dosage as appropriate and monitor clinical/oncologic response.
What happens
Reduced exposure to CYP3A substrate and an increased risk of therapeutic failure
Interaction Deep Dive
Do not combine sotorasib with a CYP3A substrate in cases where even small shifts in concentration could cause therapeutic failure. Clinical study data showed that giving sotorasib together with midazolam (a CYP3A substrate) produced a marked reduction in midazolam exposure. Should the combination be necessary, raise the dose of the CYP3A substrate as appropriate1.
Why it happens (mechanism)
Induction of CYP3A substrate metabolism by sotorasib
How to manage this interaction
What your care team may do:
- Try to avoid using these two together when possible, since even small drops in abemaciclib levels could reduce how well it works.
- If you do need both, your abemaciclib dose may need to be adjusted and individualized by your oncology team.
- Your team may monitor you more closely to make sure the treatment is still working.
What you should do: Keep taking both medicines exactly as prescribed. Don't adjust anything yourself. Let your pharmacist or oncologist know you're on both so they can plan the safest approach and answer your questions.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical trial, administering sotorasib together with midazolam (a sensitive CYP3A substrate) reduced midazolam exposure, with Cmax lowered by 48% and AUC lowered by 53% 1.
Common questions
Can I take Abemaciclib and Sotorasib together?
Sotorasib may lower abemaciclib levels and make it less effective, so your oncology team will try to avoid the combination or adjust your abemaciclib dose and monitor your response. Keep taking both as prescribed and talk with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Sotorasib 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 Sotorasib interaction managed?
What your care team may do: Try to avoid using these two together when possible, since even small drops in abemaciclib levels could reduce how well it works. If you do need both, your abemaciclib dose may need to be adjusted and individualized by your oncology team. Your team may monitor you more closely to make sure the treatment is still working. What you should do: Keep taking both medicines ex… 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 Sotorasib 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: LUMAKRAS(TM) oral tablets, sotorasib oral tablets. Amgen Inc (per FDA), Thousand Oaks, CA, 2021. DailyMed
Keep reading about Abemaciclib
Keep reading about Sotorasib
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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