Cariprazine and Berotralstat: 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
Berotralstat
Cariprazine
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.
These two medicines can interact. Berotralstat (Orladeyo) slows down the enzyme in your body that breaks down cariprazine (Vraylar). Because of this, cariprazine and its active byproduct can build up higher than expected. That could make cariprazine's side effects more likely, like restlessness, trouble sleeping, muscle stiffness, or feeling shaky or drowsy.
The good news is your care team knows how to handle this. They can lower your cariprazine dose or space it out (for example, every other day) so it stays effective and comfortable. Please don't change anything on your own. Just keep taking both as prescribed and check in with your doctor or pharmacist so they can tailor the dose to you.
Mechanism: Berotralstat is a moderate CYP3A4 inhibitor; cariprazine is a CYP3A4 substrate. Coadministration reduces metabolism, increasing exposure (AUC/Cmax) of cariprazine and its active metabolite didesmethylcariprazine (long half-life, prolonged accumulation).
Direction: Increased cariprazine effect and dose-related adverse effects (EPS, akathisia, sedation). Evidence: probable; severity: major.
Management (per labeling):
- Initiating cariprazine on inhibitor (schizophrenia/bipolar mania): 1.5 mg every other day, titrate per response/tolerability.
- Bipolar depression/MDD adjunct: 1.5 mg every other day.
- Adding inhibitor to stable cariprazine: if on 1.5 or 3 mg daily, reduce to 1.5 mg every other day; if on 4.5 or 6 mg daily, reduce to 1.5 mg daily.
- On inhibitor discontinuation, dose may need upward adjustment per response.
What happens
Increased cariprazine and its major active metabolite (didesmethylcariprazine (DDCAR)) exposure
Interaction Deep Dive
Taking cariprazine (which is metabolized by CYP3A4) together with a moderate CYP3A4 inhibitor can raise the levels of both cariprazine and its active metabolite, didesmethylcariprazine. If cariprazine therapy is being started in a patient already receiving a moderate CYP3A4 inhibitor (for schizophrenia or bipolar mania), begin with 1.5 mg orally every other day, and titrate up to 1.5 mg orally every other day if warranted, guided by clinical response and how well it is tolerated. For patients on a moderate CYP3A4 inhibitor being treated for bipolar depression or as add-on therapy for MDD, the dose is 1.5 mg orally every other day. When a moderate CYP3A4 inhibitor is added to an established cariprazine regimen: for those currently receiving 1.5 or 3 mg once daily, reduce cariprazine to 1.5 mg orally every other day upon starting the inhibitor. For those currently on cariprazine 4.5 or 6 mg once daily, change cariprazine to 1.5 mg orally once daily when the inhibitor is started. Should the moderate CYP3A4 inhibitor be stopped, the cariprazine dose may require an increase according to clinical response and tolerability1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of cariprazine
How to manage this interaction
The key here is dose adjustment and monitoring, which your care team manages. Because berotralstat can raise cariprazine levels, your prescriber may lower your cariprazine dose or have you take it less often (for example, every other day), depending on your dose and what you are treating.
- Keep taking both exactly as prescribed unless told otherwise.
- Watch for increased side effects like restlessness, stiffness, tremor, or drowsiness, and report them.
- Tell your team if either medicine is started or stopped, since the cariprazine dose may need to be raised again after berotralstat is discontinued.
Your dose will be individualized and monitored so it stays both safe and effective.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction studies, giving cariprazine 1.5 mg/day together with erythromycin (a moderate CYP3A4 inhibitor) 500 mg twice daily for 21 days led to an increase in cariprazine AUC (0 to 24 hours) and Cmax of roughly 50% 1. In one study that enrolled only White males taking cariprazine 1.5 mg/day and erythromycin 500 mg twice daily (n=40), AUCs rose by 38% (cariprazine), 11% (desmethylcariprazine, an active metabolite), and 60% (didesmethylcariprazine, an active metabolite), and Cmax rose by 34%, 16%, and 62%, respectively. Tmax was not affected by coadministration with erythromycin 2.
Common questions
Can I take Cariprazine and Berotralstat together?
Berotralstat can raise cariprazine levels and side effects, so your doctor will likely lower or space out your cariprazine dose. Keep taking both as prescribed and report any new symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cariprazine and Berotralstat 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 is the Cariprazine and Berotralstat interaction managed?
The key here is dose adjustment and monitoring, which your care team manages. Because berotralstat can raise cariprazine levels, your prescriber may lower your cariprazine dose or have you take it less often (for example, every other day), depending on your dose and what you are treating. Keep taking both exactly as prescribed unless told otherwise. Watch for increased side effects like restlessne… Management is individual — always follow your own care team's guidance.
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 Cariprazine or Berotralstat 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)
- Product Information: VRAYLAR(R) oral capsules, cariprazine oral capsules. AbbVie Inc. (per FDA), North Chicago, IL, 2024. DailyMed
- Szabo M, Hujber Z, Harsanyi J, et al: Coadministration of cariprazine with a moderate CYP3A4 inhibitor in patients with schizophrenia: implications for dose adjustment and safety monitoring. Clin Pharmacokinet 2024; 63(10):1501-1510. PubMed
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