Abemaciclib and Tucatinib: 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
Tucatinib
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.
These two cancer medicines can interact. Tucatinib (Tukysa) slows down a liver enzyme called CYP3A that your body uses to break down abemaciclib (Verzenio). When that enzyme is blocked, abemaciclib can build up in your blood to higher levels than intended.
Higher abemaciclib levels can mean more side effects, such as diarrhea, low blood counts, tiredness, or liver problems. The good news is your cancer team knows about this. They can adjust your abemaciclib dose and watch you more closely to keep you safe. Please don't stop or change either medicine on your own. Talk with your oncologist or pharmacist about the best plan.
Effect: Tucatinib is a strong CYP3A4 inhibitor; abemaciclib is a CYP3A4 substrate. Coadministration inhibits abemaciclib metabolism, increasing its exposure (AUC/Cmax) and risk of dose-dependent toxicity.
- Direction: Increased abemaciclib effect and toxicity (neither is a prodrug requiring activation).
- Magnitude: Tucatinib markedly increased midazolam (sensitive CYP3A substrate) AUC/Cmax; expect a clinically meaningful rise in abemaciclib exposure.
- Evidence: Probable; Severity: major; onset unspecified.
- Management: Avoid combination if feasible; if required, reduce the abemaciclib dose per labeling and monitor for diarrhea, hepatotoxicity, myelosuppression, and fatigue.
What happens
Increased exposure to CYP3A substrate and risk of toxicity
Interaction Deep Dive
Do not use tucatinib together with a CYP3A substrate in cases where even small shifts in concentration could cause serious or life-threatening toxicities. A clinical study showed that giving tucatinib alongside midazolam (a CYP3A substrate) produced a marked rise in both the AUC and Cmax of midazolam. When the two must be given together, lower the dose of the CYP3A substrate1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by tucatinib
How to manage this interaction
Your care team can manage this combination safely with a few steps:
- They may avoid using both together when possible, or choose an alternative.
- If both are needed, your abemaciclib dose may be reduced and individualized to your situation.
- They may monitor you more closely for side effects like diarrhea, low blood counts, and liver changes.
What you can do: keep taking both exactly as prescribed unless told otherwise, and report new or worsening diarrhea, unusual tiredness, or signs of infection. Ask your oncologist or pharmacist before starting, stopping, or changing either drug.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical trial, giving a single 2 mg dose of midazolam (a CYP3A substrate with a narrow therapeutic index) together with steady-state tucatinib 300 mg twice daily produced a ratio of midazolam exposure with versus without tucatinib of 5.7 for AUC and 3 for Cmax 1.
Common questions
Can I take Abemaciclib and Tucatinib together?
Tucatinib blocks the enzyme that clears abemaciclib, raising abemaciclib levels and side-effect risk; your team will avoid the combination or lower the abemaciclib dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Tucatinib 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 Tucatinib interaction managed?
Your care team can manage this combination safely with a few steps: They may avoid using both together when possible, or choose an alternative. If both are needed, your abemaciclib dose may be reduced and individualized to your situation. They may monitor you more closely for side effects like diarrhea, low blood counts, and liver changes. What you can do: keep taking both exactly as prescribed un… 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 Abemaciclib or Tucatinib 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: TUKYSA(TM) oral tablets, tucatinib oral tablets. Seattle Genetics Inc (per FDA), Bothell, WA, 2020. DailyMed
Keep reading about Tucatinib
Keep reading about Abemaciclib
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.
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