Brexpiprazole and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Brexpiprazole
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 brexpiprazole exposure
Interaction Deep Dive
Concomitant use of brexpiprazole (a CYP3A4 substrate) and a strong CYP3A4 inducer may reduce brexpiprazole exposure. Dosage modifications are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant strong CYP3A4 inducers. In CYP2D6 poor metabolizers, administer half of the recommended dosage. If concurrent use is required, double the usual brexpiprazole dose over a 1- to 2-week period during coadministration. Reduce brexpiprazole to original dosage over 1 to 2 weeks if concurrent inducer is discontinued. In a drug interaction study, coadministration of brexpiprazole and rifAMPin (strong CYP3A4 inducer) may increase brexpiprazole AUC(0 to inf) by approximately 0.25-fold1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of brexpiprazole
Literature reports
1 report — tap to read
a) In a drug interaction study, coadministration of brexpiprazole and rifAMPin (strong CYP3A4 inducer) may increase brexpiprazole AUC(0 to inf) by approximately 0.25-fold 1.
Common questions
Can I take Brexpiprazole and Phenytoin together?
Reduced brexpiprazole exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Brexpiprazole 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Brexpiprazole 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 (1)
- Product Information: REXULTI(R) oral tablets, brexpiprazole oral tablets. Otsuka America Pharmaceutical, Inc. (per Manufacturer), Rockville, MD, 2025. DailyMed
Keep reading about Phenytoin
Keep reading about Brexpiprazole
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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