Phenytoin and Abemaciclib: 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
Phenytoin
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. Phenytoin (Dilantin) speeds up the body's system that breaks down abemaciclib (Verzenio), which is a cancer medicine. When that happens, your body clears the abemaciclib faster, so there's less of it in your blood. That means it may not work as well against the cancer, which is the real concern here.
In studies, a similar strong booster drug cut abemaciclib levels by about two-thirds, so this matters. Please don't change anything on your own. Let your oncology team know you take both, and they can pick a safer combination or make a plan that keeps your treatment working.
Effect: Phenytoin, a strong CYP3A4 inducer, is expected to increase abemaciclib metabolism, lowering plasma concentrations of abemaciclib and its active metabolites and risking reduced antitumor efficacy.
- Mechanism: Induction of CYP3A4-mediated abemaciclib metabolism (PK, reduced exposure).
- Magnitude: Rifampin (strong inducer) reduced abemaciclib AUC by ~67%; similar effect anticipated with phenytoin.
- Direction: Reduced abemaciclib effect (neither drug is a prodrug in this context).
- Evidence/onset: Theoretical for phenytoin; onset unspecified.
- Management: Avoid coadministration; consider a non-inducing alternative anticonvulsant. If unavoidable, individualize and monitor efficacy closely.
What happens
Decreased abemaciclib plasma concentration
Interaction Deep Dive
When abemaciclib is taken together with a potent CYP3A4 inducer, plasma concentrations of both abemaciclib and its active metabolite can fall, potentially reducing therapeutic effectiveness. Study data showed that giving rifampin (a strong CYP3A4 inducer) alongside abemaciclib reduced abemaciclib exposure by 67%. This combination should not be used, and clinicians should look at alternative agents1.
Why it happens (mechanism)
Induction of CYP3A4-mediated abemaciclib metabolism
How to manage this interaction
The main worry is that phenytoin can make abemaciclib less effective by lowering its levels in your blood. Because of this, the general guidance is to avoid using these two together and consider an alternative.
- Keep taking both exactly as prescribed until your care team advises otherwise. Do not stop either on your own.
- Tell your oncologist and pharmacist that you take both drugs.
- Your team may choose a different seizure medicine that does not speed up abemaciclib's breakdown.
- If both must be used, your team can monitor your response more closely and tailor the plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In studies of drug interactions conducted in healthy volunteers, giving a single 200 mg dose of abemaciclib together with rifampin 600 mg daily (a potent CYP3A inducer) reduced the AUC(0 to infinity) of abemaciclib along with its active metabolites (M2, M18, and M20) by 67% 1.
Common questions
Can I take Phenytoin and Abemaciclib together?
Phenytoin can significantly lower abemaciclib levels and reduce how well it treats your cancer, so this combination is best avoided. Talk to your oncology team about a safer alternative. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Abemaciclib 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 Phenytoin and Abemaciclib interaction managed?
The main worry is that phenytoin can make abemaciclib less effective by lowering its levels in your blood. Because of this, the general guidance is to avoid using these two together and consider an alternative. Keep taking both exactly as prescribed until your care team advises otherwise. Do not stop either on your own. Tell your oncologist and pharmacist that you take both drugs. Your team may ch… 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 Phenytoin or Abemaciclib 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: VERZENIO(TM) oral tablets, abemaciclib oral tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2017. DailyMed
Keep reading about Phenytoin
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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