Abemaciclib and Nefazodone: 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
Nefazodone
No brand names on recordAbemaciclib
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. Nefazodone is a strong blocker of a liver enzyme (called CYP3A4) that your body uses to break down abemaciclib (Verzenio). When that enzyme is slowed down, abemaciclib can build up to higher levels in your blood. That can mean more side effects, like diarrhea, nausea, tiredness, or a drop in blood counts.
The good news is that this is very manageable. Your care team may lower your Verzenio dose while you take these together, and watch you a bit more closely. Please don't change anything on your own. Just check with your pharmacist or doctor so they can tailor the dose safely for you.
Mechanism: Nefazodone is a strong CYP3A4 inhibitor. Abemaciclib is a CYP3A4 substrate (and its active metabolites are also CYP3A4-dependent), so inhibition reduces clearance and raises abemaciclib exposure (AUC/Cmax), increasing toxicity risk.
Direction: increased abemaciclib effect/toxicity. Evidence: theoretical. Onset: unspecified.
Management per labeling:
- Starting dose 200 or 150 mg BID: reduce to 100 mg BID.
- Already reduced to 100 mg BID for adverse reactions: reduce further to 50 mg BID.
- On inhibitor discontinuation, after 3 to 5 inhibitor half-lives, resume the pre-inhibitor dose.
Monitor for GI toxicity, fatigue, hepatotoxicity, and myelosuppression.
What happens
Increased abemaciclib plasma concentration
Interaction Deep Dive
Taking abemaciclib together with a potent CYP3A4 inhibitor can raise plasma concentrations of both abemaciclib and its active metabolite, potentially increasing toxicity. When these agents are given together and abemaciclib was initiated at either 200 mg or 150 mg twice daily, lower the abemaciclib dose to 100 mg twice daily. For patients whose dose has already been decreased to 100 mg twice daily because of adverse reactions, cut the abemaciclib dose further to 50 mg twice daily. Once the strong CYP3A inhibitor has been stopped, wait 3-5 half-lives of the inhibitor and then raise the abemaciclib dose back to the level used prior to starting the strong inhibitor1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated abemaciclib metabolism
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This interaction is well understood and can be managed.
Here is what your team typically does:
- Lower the Verzenio dose while you are on nefazodone (for example, stepping down from a higher starting dose, and lowering it further if you had already been reduced for side effects).
- Watch you more closely for side effects like diarrhea, nausea, fatigue, and blood-count changes.
- Return to your prior dose a few days after nefazodone is stopped, once it clears your system.
Tell your pharmacist or prescriber you take both, and report any new or worsening side effects.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In drug interaction studies, giving abemaciclib together with itraconazole (a strong CYP3A inhibitor) is expected to raise the AUC of abemaciclib and its active metabolites (M2, M18 and M20) by 2.2-fold 1.
b) In drug interaction studies conducted in cancer patients, administering a single 50 mg dose of abemaciclib (0.3 times the approved 150 mg dose) alongside clarithromycin 500 mg twice daily (a strong CYP3A inhibitor) raised the AUC(0 to infinity) of abemaciclib plus its active metabolites (M2, M18, and M20) by 1.7-fold relative to abemaciclib given alone 1.
Common questions
Can I take Abemaciclib and Nefazodone together?
Nefazodone can raise abemaciclib levels and side effects by blocking the enzyme that clears it; your care team can manage this by lowering the Verzenio dose and monitoring you more closely. Do not change either medication on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Nefazodone 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 Nefazodone interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This interaction is well understood and can be managed. Here is what your team typically does: Lower the Verzenio dose while you are on nefazodone (for example, stepping down from a higher starting dose, and lowering it further if you had already been reduced for side effects). Watch you more closely for side effects… 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 Nefazodone 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: VERZENIO(TM) oral tablets, abemaciclib oral tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2017. DailyMed
Keep reading about Nefazodone
Keep reading about Abemaciclib
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