Mitotane 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
Mitotane
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. Mitotane (Lysodren) speeds up a liver enzyme called CYP3A4, which is the same enzyme that breaks down your cancer medicine abemaciclib (Verzenio). When Mitotane revs up that enzyme, your body clears abemaciclib faster, so there's less of it in your blood.
The concern here is not more side effects, but the opposite: abemaciclib may not work as well as it should. Because Verzenio is treating your cancer, keeping it working is really important. Please don't stop or change either medicine on your own. Talk with your oncology team, they can look at your combination and pick the safest, most effective plan for you.
Interaction: Mitotane is a potent CYP3A4 inducer; abemaciclib is a CYP3A4 substrate (and its active metabolites also depend on this pathway). Enzyme induction accelerates abemaciclib metabolism, lowering plasma exposure of the parent drug and active metabolites, risking reduced antitumor efficacy.
- Direction: reduced abemaciclib effect (PK-driven loss of exposure).
- Magnitude: rifampin (strong inducer) decreased abemaciclib AUC ~67%; mitotane is expected to be similar.
- Onset: unspecified; note mitotane induction is prolonged given its long half-life.
- Evidence: theoretical, extrapolated from strong-inducer data.
- Management: avoid combination; select an alternative agent. If unavoidable, dose individualization and closer monitoring of response by the care team.
What happens
Decreased abemaciclib plasma concentration
Interaction Deep Dive
Taking abemaciclib together with a potent CYP3A4 inducer can lower the plasma concentrations of both abemaciclib and its active metabolite, potentially reducing its effectiveness. Research showed that pairing it with rifampin, a strong CYP3A4 inducer, reduced abemaciclib exposure by 67%. This combination should not be used, and alternative agents should be considered1.
Why it happens (mechanism)
Induction of CYP3A4-mediated abemaciclib metabolism
How to manage this interaction
What your care team may do:
- Because Mitotane can substantially lower abemaciclib levels, the label advises avoiding this combination and considering an alternative medication.
- Your oncology team may select a different drug for one of these roles, or adjust and individualize your plan and monitor your response more closely.
What you can do:
- Keep taking both exactly as prescribed until your team tells you otherwise.
- Make sure every prescriber and your pharmacist know you take both, so they can review your regimen.
- Report any sense that your treatment may not be working as expected.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction investigations conducted in healthy participants, giving a single 200 mg dose of abemaciclib together with rifampin 600 mg daily (a strong inducer of CYP3A) reduced the AUC(0 to infinity) of abemaciclib together with its active metabolites (M2, M18, and M20) by 67% 1.
Common questions
Can I take Mitotane and Abemaciclib together?
Mitotane can significantly lower abemaciclib levels and may make it less effective, so this combination is usually avoided. Talk with your oncology team, they can choose an alternative or adjust your plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mitotane 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 Mitotane and Abemaciclib interaction managed?
What your care team may do: Because Mitotane can substantially lower abemaciclib levels, the label advises avoiding this combination and considering an alternative medication. Your oncology team may select a different drug for one of these roles, or adjust and individualize your plan and monitor your response more closely. What you can do: Keep taking both exactly as prescribed until your team tel… 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 Mitotane 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: VERZENIO(TM) oral tablets, abemaciclib oral tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2017. DailyMed
Keep reading about Mitotane
Keep reading about Abemaciclib
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