Abemaciclib and Selpercatinib: 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
Selpercatinib
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. Your cancer medicine abemaciclib (Verzenio) is broken down in your body by a liver enzyme called CYP3A. The other drug, selpercatinib (Retevmo), can slow that enzyme down a bit. When the enzyme works slower, abemaciclib can build up higher than usual, which may mean more side effects like diarrhea, tiredness, nausea, or low blood counts.
This is based mostly on how the drugs work rather than on lots of patient reports, so please don't panic. The good news is your care team knows how to handle this. They can adjust your dose and keep a closer eye on how you're feeling. Never change your doses on your own, but do bring this up with your oncologist or pharmacist.
Mechanism: Selpercatinib is a weak CYP3A inhibitor; abemaciclib is a CYP3A substrate (not a prodrug). Inhibition reduces abemaciclib clearance, increasing exposure (AUC/Cmax) and the risk of dose-related toxicity (diarrhea, neutropenia, hepatotoxicity, fatigue).
- Direction: increased abemaciclib exposure and adverse-effect risk.
- Magnitude: not quantified for this pair; selpercatinib raised sensitive substrate midazolam AUC by ~54% and Cmax by ~39%.
- Onset: unspecified.
- Evidence: theoretical.
- Management: avoid combination where minimal concentration changes may cause harm; if necessary, consider abemaciclib dose reduction and monitor for toxicity (CBC, LFTs, GI symptoms).
What happens
Increased substrate exposure and an increased risk for adverse effects
Interaction Deep Dive
Do not give selpercatinib, a weak CYP3A inhibitor, together with a CYP3A substrate for which even small changes in concentration could trigger adverse reactions. A pharmacokinetic study showed that combining it with midazolam, a sensitive CYP3A substrate, raised midazolam AUC (0 to inf) by 54% and Cmax by 39%. When it is necessary to use selpercatinib alongside such a CYP3A substrate, reducing the substrate dose should be considered, as appropriate1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by selpercatinib
How to manage this interaction
How your team typically handles this:
- They may avoid using these two together when possible, since even small increases in abemaciclib levels can matter.
- If both are needed, they may reduce the abemaciclib dose and individualize it for you.
- They may monitor you more closely, watching for side effects such as diarrhea, unusual tiredness, or signs of low blood counts, and checking labs as they see fit.
What you should do: Keep taking both medicines exactly as prescribed. Don't stop or change a dose on your own. Tell your pharmacist or oncologist about all your medicines, and report new or worsening side effects promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) During a pharmacokinetic study, giving selpercatinib together with midazolam (a sensitive CYP3A substrate) raised the midazolam AUC (0 to inf) by 54% and the Cmax by 39% 1.
Common questions
Can I take Abemaciclib and Selpercatinib together?
Selpercatinib can raise abemaciclib levels and side-effect risk by slowing its breakdown, so your care team may lower the abemaciclib dose and watch you more closely. Keep taking both as prescribed and report new side effects. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Selpercatinib 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 Selpercatinib interaction managed?
How your team typically handles this: They may avoid using these two together when possible, since even small increases in abemaciclib levels can matter. If both are needed, they may reduce the abemaciclib dose and individualize it for you. They may monitor you more closely, watching for side effects such as diarrhea, unusual tiredness, or signs of low blood counts, and checking labs as they see f… 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 Selpercatinib 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: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Abemaciclib
Keep reading about Selpercatinib
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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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