Phenytoin and Afatinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Afatinib
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
Decreased afatinib exposure
Interaction Deep Dive
Concurrent use of afatinib (a P-glycoprotein (P-gp) substrate) and a P-gp inducer may decrease the exposure of afatinib. When coadministration of afatinib with rifampicin (a P-gp inducer) was studied, pretreatment with rifampicin 600 mg daily for 7 days decreased afatinib AUC and Cmax by 34% and 22%, respectively, compared with oral administration of afatinib alone. Therefore, if chronic coadministration of afatinib and a P-gp inducer is necessary, increase the afatinib daily dose by 10 mg. If chronic concurrent P-gp inducer therapy is discontinued, resume the previous afatinib dose 2 to 3 days after discontinuation of the P-gp inducer1.
Why it happens (mechanism)
Induction of P-glycoprotein-mediated efflux transport of afatinib
Literature reports
1 report — tap to read
a) In a pharmacokinetic evaluation, pretreatment with rifampicin 600 mg once daily for 7 days decreased the afatinib AUC(0 to infinity) and Cmax by 34% and 22%, respectively 1.
Common questions
Can I take Phenytoin and Afatinib together?
Decreased afatinib exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Afatinib 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 Phenytoin or Afatinib 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: GILOTRIF(TM) oral tablets, afatinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc. (per FDA), Ridgefield, CT, 2013. DailyMed
Keep reading about Phenytoin
Keep reading about Afatinib
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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