Abemaciclib and Fosphenytoin: 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
Fosphenytoin
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. Fosphenytoin is a seizure medicine that speeds up a liver enzyme (called CYP3A4) that your body uses to break down abemaciclib, your cancer medicine. When that enzyme works faster, your body clears abemaciclib more quickly, so the level in your blood can drop. In one study, a similar strong enzyme booster (rifampin) cut abemaciclib exposure by about 67%.
The worry here is too little cancer medicine, which could make it work less well. This is expected based on how these drugs behave, not something proven with this exact pair. Please don't change anything on your own. Your care team can look at safer options and keep a close eye on you.
Mechanism: Fosphenytoin (converted to phenytoin) is a strong CYP3A4 inducer. Abemaciclib is a CYP3A4 substrate, so induction increases its metabolism.
Effect / direction: Decreased abemaciclib and active-metabolite plasma concentrations, risking reduced antitumor efficacy. Analogous rifampin data showed a ~67% reduction in abemaciclib exposure (AUC).
- Severity: Major
- Onset: Unspecified (induction typically develops over days to weeks)
- Evidence: Theoretical, extrapolated from strong-inducer data
Management: Avoid coadministration. Select an alternative anticonvulsant that does not induce CYP3A4, or an alternative to abemaciclib, per the oncology and neurology teams.
What happens
Decreased abemaciclib plasma concentration
Interaction Deep Dive
When abemaciclib is taken together with a potent CYP3A4 inducer, plasma concentrations of abemaciclib along with its active metabolite can fall, potentially reducing therapeutic effect. Study data showed that giving rifampin, a strong CYP3A4 inducer, alongside abemaciclib lowered abemaciclib exposure by 67%. This combination should not be used, and alternative agents ought to be considered1.
Why it happens (mechanism)
Induction of CYP3A4-mediated abemaciclib metabolism
How to manage this interaction
What your care team may do:
- Because this combination can lower your cancer medicine's effectiveness, they typically try to avoid using them together.
- They may consider an alternative seizure medicine that does not speed up this liver enzyme, or a different approach to your cancer treatment.
- If both are truly needed, they may monitor you more closely.
What you should do:
- Keep taking both exactly as prescribed for now.
- Tell your oncologist and pharmacist that you take both drugs so they can coordinate.
- Do not start, stop, or change either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction trials conducted in healthy volunteers, giving a single 200 mg dose of abemaciclib together with rifampin 600 mg once 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 Abemaciclib and Fosphenytoin together?
Fosphenytoin can lower abemaciclib levels and make it work less well, so this combination is usually avoided. Let your oncologist and pharmacist know you take both so they can pick a safer option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abemaciclib and Fosphenytoin 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 Fosphenytoin interaction managed?
What your care team may do: Because this combination can lower your cancer medicine's effectiveness, they typically try to avoid using them together. They may consider an alternative seizure medicine that does not speed up this liver enzyme, or a different approach to your cancer treatment. If both are truly needed, they may monitor you more closely. What you should do: Keep taking both exactly as… 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 Fosphenytoin 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 Fosphenytoin
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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