Abemaciclib and Lonafarnib: 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
Lonafarnib
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. Lonafarnib (Zokinvy) slows down a liver enzyme called CYP3A. Your other medicine, abemaciclib (Verzenio), is broken down by that same enzyme. So when you take them together, abemaciclib can build up higher in your body than it should.
That extra buildup can mean more of abemaciclib's side effects, like diarrhea, low blood counts, or feeling very tired. The good news is this is something your care team can plan for. They may adjust your abemaciclib dose or watch you more closely. Please don't stop or change either medicine on your own. Just talk with your oncologist or pharmacist so they can tailor things safely for you.
Mechanism: Lonafarnib is a CYP3A inhibitor; abemaciclib is a CYP3A4 substrate (active drug, not a prodrug). Inhibition reduces abemaciclib clearance, raising exposure (AUC/Cmax) and the risk of dose-related toxicity.
- Direction: Increased abemaciclib exposure and adverse effects (diarrhea, neutropenia, hepatotoxicity, fatigue).
- Magnitude: Not established for this pair; lonafarnib raised midazolam AUC ~639% and loperamide AUC ~299% in healthy subjects, indicating strong inhibition.
- Evidence: Theoretical/extrapolated. Onset: unspecified.
- Management: Avoid concomitant use where possible; if unavoidable, monitor for abemaciclib toxicity and reduce dose as needed.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
The combination of lonafarnib, which inhibits CYP3A, with sensitive CYP3A substrates that have a narrow therapeutic index (NTI) should be avoided, because lonafarnib raises the exposure of these NTI CYP3A substrates and can thereby heighten the likelihood of adverse reactions associated with them. In healthy subjects who received a single 2 mg oral dose of loperamide (a CYP3A substrate) together with lonafarnib 100 mg given orally twice daily over 5 days, loperamide Cmax rose by 214% and its AUC by 299%. Similarly, when healthy subjects took a single 3 mg oral dose of midazolam (a CYP3A substrate) alongside lonafarnib 100 mg orally twice daily for 5 days, midazolam Cmax increased by 180% and its AUC by 639%. When it is not possible to avoid giving other sensitive CYP3A substrates together with lonafarnib, watch for adverse reactions and, where necessary, lower the dose of the sensitive CYP3A substrate with NTI1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by lonafarnib
How to manage this interaction
What your team may do:
- Prefer to avoid using these two together when possible.
- If both are needed, they may reduce your abemaciclib dose and individualize it for you.
- They may monitor you more closely for abemaciclib side effects, such as diarrhea, signs of low blood counts (fever, infections), or liver-related symptoms.
What you can do: Keep taking both medicines exactly as prescribed unless told otherwise. Tell your pharmacist or oncologist that you take both, and report any new or worsening side effects promptly so they can adjust things.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a clinical study in healthy subjects, when a single oral 2 mg dose of loperamide (a CYP3A substrate) was given together with multiple oral doses of lonafarnib 100 mg twice daily over 5 days, the loperamide Cmax rose by 214% and its AUC rose by 299% 1.
b) In a clinical study in healthy subjects, when a single oral 3 mg dose of midazolam (a CYP3A substrate) was administered along with multiple oral doses of lonafarnib 100 mg twice daily over 5 days, the midazolam Cmax increased by 180% and its AUC increased by 639% 1.
Common questions
Can I take Abemaciclib and Lonafarnib together?
Lonafarnib can raise abemaciclib levels and increase its side effects, so your care team may avoid the combination or lower and closely monitor your abemaciclib dose. Don't change either medicine on your own; check with your oncologist or pharmacist. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Lonafarnib 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 Lonafarnib interaction managed?
What your team may do: Prefer to avoid using these two together when possible. If both are needed, they may reduce your abemaciclib dose and individualize it for you. They may monitor you more closely for abemaciclib side effects, such as diarrhea, signs of low blood counts (fever, infections), or liver-related symptoms. What you can do: Keep taking both medicines exactly as prescribed unless told… 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 Lonafarnib 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: ZOKINVY(TM) oral capsules, lonafarnib oral capsules. Eiger BioPharmaceuticals Inc (per FDA), Palo Alto, CA, 2024. DailyMed
Keep reading about Lonafarnib
Keep reading about Abemaciclib
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