Drug Interaction Report

Cariprazine and Rilzabrutinib: Interaction Details

AI-assisted, pharmacist-reviewed · AI content regenerated Jul 16, 2026 · Source data updated Jul 16, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Rilzabrutinib

Wayrilz
+

Cariprazine

Vraylar Vraylar®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 16, 2026
LinkedIn
Interaction severity
Moderate
Can be significant — usually manageable with 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 157 documented Cariprazine interactions, 4 are rated moderate — including this one.
At a glance + Theoretical Effects may be stronger
The Bottom Line
Rilzabrutinib can raise cariprazine levels and side effects because it slows the enzyme that clears cariprazine, so your care team may watch you more closely and adjust your cariprazine dose. Keep taking both as prescribed and report any new or worsening symptoms.

You've been prescribed two medicines that can interact. Rilzabrutinib (Wayrilz) slows down a liver enzyme called CYP3A. Your antipsychotic, cariprazine (Vraylar), is broken down by that same enzyme. So when you take them together, cariprazine can build up in your body and reach higher levels than usual.

That could mean more of cariprazine's usual side effects, like feeling drowsy, restless, dizzy, or having a bit of trouble with movement. The good news is that this is a manageable situation. Your care team can watch you a little more closely and adjust your cariprazine dose if needed. Please don't stop or change either medicine on your own talk with your pharmacist or doctor first.

Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor; cariprazine is a CYP3A4 substrate. Inhibition reduces cariprazine clearance, increasing its exposure (AUC/Cmax) and that of its active metabolites (DDCAR, DCAR), which have long half-lives.

Direction: Increased cariprazine effect and adverse-reaction risk (neither drug is a prodrug requiring activation here).

  • Magnitude: Theoretical for this pair; rilzabrutinib raised midazolam AUC ~2.2 to 3.0-fold.
  • Onset: Unspecified; note prolonged washout given cariprazine metabolite half-lives.
  • Evidence: Theoretical.
  • Management: Monitor for dose-related effects (EPS, akathisia, sedation, akinesia); consider cariprazine dose reduction and individualize.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions

Interaction Deep Dive

When rilzabrutinib, a moderate inhibitor of CYP3A, is given together with CYP3A substrates, exposure to those substrates can rise, thereby heightening the likelihood of adverse reactions tied to the substrates. Increase the frequency of monitoring for adverse reactions of the co-administered CYP3A substrate and adjust its dosage as appropriate. A drug interaction study conducted in healthy participants showed that giving a single 400 mg dose of rilzabrutinib alongside midazolam (a sensitive CYP3A substrate) raised both the Cmax and AUC of midazolam by 2.2-fold. Modeling predicts that, in patients with immune thrombocytopenia receiving 400 mg rilzabrutinib twice daily, midazolam AUC could increase by as much as 3.0-fold1.

Why it happens (mechanism)

Inhibition of CYP3A-substrate metabolism by rilzabrutinib

How to manage this interaction

This interaction is manageable with a few sensible steps from your care team:

  • Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
  • Your team may monitor you more closely for cariprazine side effects such as drowsiness, restlessness, dizziness, or muscle stiffness and movement changes.
  • Your cariprazine dose may be adjusted and individualized by your care team while you are on both drugs.

Let your pharmacist or doctor know if you notice new or stronger side effects. Because cariprazine and its active byproducts stay in the body a long time, tell them if either medicine is started or stopped.

Management is individual — confirm any change with your pharmacist or prescriber.

Literature reports

1 report — tap to read

a) In a drug interaction study conducted in healthy volunteers, giving a single 400 mg dose of rilzabrutinib together with midazolam (a sensitive CYP3A substrate) raised the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise by as much as 3.0-fold when combined with rilzabrutinib 400 mg twice daily 1.

Common questions

Can I take Cariprazine and Rilzabrutinib together?

Rilzabrutinib can raise cariprazine levels and side effects because it slows the enzyme that clears cariprazine, so your care team may watch you more closely and adjust your cariprazine dose. Keep taking both as prescribed and report any new or worsening symptoms. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Cariprazine and Rilzabrutinib interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How is the Cariprazine and Rilzabrutinib interaction managed?

This interaction is manageable with a few sensible steps from your care team: Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for cariprazine side effects such as drowsiness, restlessness, dizziness, or muscle stiffness and movement changes. Your cariprazine dose may be adjusted and individualized by your care team… 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 Cariprazine or Rilzabrutinib 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 anything you'd monitor while I'm on both?

References (1)

  1. Product Information: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
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