Everolimus and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Everolimus
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.
What happens
Reduced everolimus exposure and reduced efficacy of everolimus
Interaction Deep Dive
Concomitant use of everolimus with strong CYP3A4/P-gp inducers may reduce the exposure of everolimus. Increase the dose of everolimus when coadministered with strong CYP3A4/P-gp inducers as recommended. For the treatment of breast cancer, progressive neuroendocrine tumors of pancreatic origin, renal cell carcinoma, or renal angiomyolipoma with tuberous sclerosis complex (TSC): avoid administration where alternative exist. If the coadministration cannot be avoided, double the daily dose using increments of 5 mg or less. Multiple increments may be required. Resume the dosage administered prior to inducer initiation, once an inducer is discontinued for 5 days. For the treatment of TSC-associated subependymal giant cell astrocytoma and TSC-associated partial-onset seizures: Double the daily dose using increments of 5 mg or less, multiple increments may be required. Addition of another strong inducer in a patient already receiving treatment with a strong CYP3A4 inducer may not require additional dosage modification. Resume dosage administered prior to inducer initiation, once the inducer is discontinued for 5 days. Assess trough concentrations when initiating and discontinuing the inducer1. If concurrent therapy is necessary in transplant recipients, closely monitor everolimus whole blood trough levels 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of everolimus; induction of P-gp mediated efflux transport of everolimus
Literature reports
1 report — tap to read
a) Coadministration of everolimus (a CYP3A4 and P-gp substrate) and rifAMPin (a strong CYP3A4 and P-gp inducer) in healthy volunteers increased the everolimus clearance nearly 3-fold, decreased Cmax by 58%, and decreased AUC by 63% 2.
Common questions
Can I take Everolimus and Phenytoin together?
Reduced everolimus exposure and reduced efficacy of everolimus Always confirm with your pharmacist or prescriber before making any change.
How serious is the Everolimus and Phenytoin 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 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 Everolimus or Phenytoin 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 (2)
Keep reading about Phenytoin
Keep reading about Everolimus
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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