Nirogacestat and Abemaciclib: 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
Nirogacestat
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 clash. Abemaciclib (Verzenio) is broken down in your body by an enzyme called CYP3A. Nirogacestat (Ogsiveo) slows that enzyme down. When the enzyme is slowed, abemaciclib can build up to higher levels than intended.
Higher levels mean a bigger chance of side effects like diarrhea, low blood counts, fatigue, or nausea. The good news is that your cancer team knows about this and can manage it. Please do not stop or change either medicine on your own. Just make sure your oncologist and pharmacist know you are taking both so they can keep you safe.
Mechanism: Nirogacestat inhibits CYP3A, reducing metabolism of the CYP3A substrate abemaciclib and increasing its systemic exposure (neither drug is functioning here as a prodrug requiring CYP3A activation).
- Direction: Increased abemaciclib AUC/Cmax, raising risk of dose-related toxicity (diarrhea, neutropenia, hepatotoxicity, fatigue).
- Magnitude: Not established for abemaciclib specifically; index probe midazolam showed Cmax up 1.77-fold and AUC up 2.07-fold with nirogacestat 150 mg BID.
- Evidence: Probable. Severity: Major. Onset: Unspecified.
- Management: Avoid concomitant use where possible; if combined, individualize the abemaciclib dose and monitor closely for toxicity.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse effects
Interaction Deep Dive
Concomitant administration of nirogacestat with CYP3A substrates should be avoided. Because nirogacestat raises the exposure of CYP3A substrates, even small changes in concentration can result in serious adverse reactions. When midazolam (a CYP3A substrate) is given together with multiple doses of nirogacestat (150 mg twice daily), its Cmax is projected to rise 1.77-fold and its AUC 2.07-fold1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by nirogacestat
How to manage this interaction
What your care team may do:
- Try to avoid using these two together when another option exists.
- If both are needed, your abemaciclib dose may be adjusted and individualized by your team.
- They may monitor you more closely, watching for side effects such as diarrhea, fatigue, or changes in blood counts.
What you should do: Keep taking both exactly as prescribed unless your doctor tells you otherwise. Report new or worsening side effects promptly, and confirm with your pharmacist or oncologist that they know you are on both drugs.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When midazolam (a CYP3A substrate) is given together with multiple doses of nirogacestat (150 mg twice daily), its Cmax is projected to rise by 1.77-fold and its AUC by 2.07-fold 1.
Common questions
Can I take Nirogacestat and Abemaciclib together?
Nirogacestat can raise abemaciclib levels and increase side effects, so this combination is usually avoided; if you must take both, your team will adjust the dose and monitor you closely. Tell your oncologist and pharmacist you are on both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nirogacestat and Abemaciclib 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 Nirogacestat and Abemaciclib interaction managed?
What your care team may do: Try to avoid using these two together when another option exists. If both are needed, your abemaciclib dose may be adjusted and individualized by your team. They may monitor you more closely, watching for side effects such as diarrhea, fatigue, or changes in blood counts. What you should do: Keep taking both exactly as prescribed unless your doctor tells you otherwise.… 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 Nirogacestat or Abemaciclib 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: OGSIVEO(TM) oral tablets, nirogacestat oral tablets. SpringWorks Therapeutics, Inc. (per FDA), Stamford, CT, 2023. DailyMed
Keep reading about Abemaciclib
Keep reading about Nirogacestat
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist