Drug Interaction Report

Brexpiprazole and Apalutamide: Interaction Details

A pharmacist-reviewed analysis of the Brexpiprazole and Apalutamide interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Apalutamide

Erleada
+

Brexpiprazole

Rexulti Rexulti®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 115 documented Brexpiprazole interactions, 106 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Reduced brexpiprazole exposure

Interaction Deep Dive

Concomitant use of apalutamide (strong CYP3A4 inducer) with brexpiprazole (CYP3A4 substrate) may result in reduced brexpiprazole exposure. Substitution of the medication primarily metabolized by CYP3A4 is recommended during apalutamide therapy. If coadministration is required, evaluate patient for loss of substrate activity2. 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 1.

Why it happens (mechanism)

Induction of CYP3A4-mediated metabolism of brexpiprazole

Literature reports

2 reports — tap to read

a) In a drug interaction study, coadministration of a single dose of apalutamide, strong CYP3A4 inducer with midazolam, CYP3A4 substrate, resulted in a 92% decrease in the midazolam AUC 2.

b) 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 Apalutamide together?

Reduced brexpiprazole exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Brexpiprazole and Apalutamide 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 Apalutamide 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)

  1. Product Information: REXULTI(R) oral tablets, brexpiprazole oral tablets. Otsuka America Pharmaceutical, Inc. (per Manufacturer), Rockville, MD, 2025. DailyMed
  2. Product Information: ERLEADA(R) oral tablets, apalutamide oral tablets. Janssen Products LP (per FDA), Horsham, PA, 2024. DailyMed
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Apalutamide

Keep reading about Apalutamide

All Apalutamide interactions (162)
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Brexpiprazole

Keep reading about Brexpiprazole

All Brexpiprazole interactions (115) Brexpiprazole drug information
Also serious with: Metoclopramide Mavorixafor Ensitrelvir Metoclopramide Injection
Beyond drug–drug

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:

Apalutamide + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 147 more
Brexpiprazole + Activated Charcoal Grapefruit Indian Snakeroot Lithium Rauvolfia Vomitoria St. John's Wort 1,3-dmaa 5-htp + 169 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.