Abemaciclib and Ranolazine: 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
Ranolazine
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. Your body uses an enzyme called CYP3A4 to break down abemaciclib (Verzenio), your cancer medicine. Ranolazine (Ranexa) slows that enzyme down. That means abemaciclib can build up higher in your blood than intended, which can make its side effects, like diarrhea, low blood counts, tiredness, or nausea, stronger.
Please don't stop or change either medicine on your own. This is something your care team knows how to handle. They may adjust your abemaciclib dose and watch you a little more closely. If you notice new or worsening side effects, let your pharmacist or doctor know so they can keep you safe.
Mechanism: Ranolazine is a moderate CYP3A4 inhibitor. Abemaciclib is a sensitive CYP3A4 substrate (not a prodrug), so inhibition reduces its metabolism and increases abemaciclib exposure (AUC/Cmax), raising toxicity risk.
- Direction: increased abemaciclib effect and adverse events (diarrhea, neutropenia, hepatotoxicity, fatigue).
- Magnitude: not quantified for this pair; ranolazine roughly doubled simvastatin exposure and increased atorvastatin ~40% (up to ~400% in one subject).
- Evidence: probable. Onset: unspecified.
- Management: consider abemaciclib dose reduction per prescribing guidance and monitor for CDK4/6 inhibitor toxicity (CBC, LFTs, GI symptoms).
What happens
Increased exposure of CYP3A4 substrate
Interaction Deep Dive
When ranolazine is given together with sensitive CYP3A4 substrates or with agents that have a narrow therapeutic index (NTI), the exposure to those substrates can rise. As a result, dosing of other sensitive CYP3A4 substrates and of CYP3A4 substrates that have a narrow therapeutic range may need to be modified. A drug interaction study in healthy volunteers showed that giving ranolazine 1000 mg twice daily alongside simvastatin 80 mg once daily, a CYP3A4 substrate, produced a 100% rise in exposure to simvastatin and its active metabolite. In the same way, coadministration of ranolazine (1000 mg twice daily) raised mean atorvastatin (80 mg daily) exposure by 40% in healthy volunteers. In one individual, however, exposure to atorvastatin and its metabolites rose by roughly 400% when ranolazine was present1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by ranolazine
How to manage this interaction
The good news is this is manageable. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- Your team may adjust and individualize your abemaciclib dose because ranolazine can raise its levels.
- They may monitor you more closely, including blood counts and liver tests, and check in about side effects.
- Watch for and report diarrhea, unusual tiredness, fever or signs of infection, or nausea.
- Tell your pharmacist and oncologist that you take both drugs, and ask before starting anything new.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study conducted in healthy volunteers, the joint administration of ranolazine 1000 mg twice daily with simvastatin 80 mg once daily, a CYP3A4 substrate, produced a 100% rise in exposure to simvastatin and its active metabolite. In a comparable manner, the mean exposure to atorvastatin (80 mg daily) rose by 40% when it was given together with ranolazine (1000 mg twice daily) in healthy volunteers. Nevertheless, in one subject the exposure to atorvastatin and its metabolites rose by roughly 400% when ranolazine was present 1.
Common questions
Can I take Abemaciclib and Ranolazine together?
Ranolazine can increase abemaciclib levels and side effects; keep taking both as prescribed, but your care team may lower the abemaciclib dose and monitor you more closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Ranolazine 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 Ranolazine interaction managed?
The good news is this is manageable. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Your team may adjust and individualize your abemaciclib dose because ranolazine can raise its levels. They may monitor you more closely, including blood counts and liver tests, and check in about side effects. Watch for and report diarrhea, unusual tiredness, fever or si… 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 Ranolazine 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: RANOLAZINE oral extended-release tablets, ranolazine oral extended-release tablets. Viona Pharmaceuticals Inc. (per Dailymed), Cranford, NJ, 2023. DailyMed
Keep reading about Ranolazine
Keep reading about Abemaciclib
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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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