Cariprazine and Crizotinib: 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
Crizotinib
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.
Here's what's going on. Your cancer medicine, crizotinib (Xalkori), slows down a liver enzyme called CYP3A4. That same enzyme is what your body uses to break down cariprazine (Vraylar). When crizotinib slows it down, cariprazine and its active form can build up higher than usual in your body.
Higher levels can mean more side effects, like restlessness, tremor, sleepiness, or trouble sitting still. The good news is this is very manageable. Your care team can lower your cariprazine dose or adjust how often you take it so both medicines work safely. Please don't change anything on your own, just talk with your pharmacist or doctor.
Mechanism: Crizotinib is a moderate CYP3A4 inhibitor; cariprazine is a CYP3A4 substrate (neither is a prodrug requiring activation). Inhibition reduces cariprazine clearance, increasing exposure of cariprazine and its long-acting active metabolite didesmethylcariprazine (DDCAR).
Direction/magnitude: Increased cariprazine/DDCAR AUC; PD effect is enhanced antipsychotic exposure (EPS, akathisia, sedation risk). Evidence: probable. Severity: major.
Management (per labeling for a moderate 3A4 inhibitor):
- Starting cariprazine on inhibitor (schizophrenia/bipolar mania): 1.5 mg every other day, titrate cautiously.
- Bipolar depression/adjunct MDD: 1.5 mg every other day.
- Stable 1.5 or 3 mg/day: reduce to 1.5 mg every other day; stable 4.5 or 6 mg/day: reduce to 1.5 mg once daily.
- On crizotinib discontinuation, re-increase 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 on a moderate CYP3A4 inhibitor (for schizophrenia or bipolar mania), begin with 1.5 mg orally every other day, then titrate up to 1.5 mg orally every other day if warranted, guided by clinical response and tolerability. For patients on a moderate CYP3A4 inhibitor being treated for bipolar depression or receiving cariprazine as adjunctive therapy for MDD, the dose is 1.5 mg orally every other day. When a moderate CYP3A4 inhibitor is added for a patient already stabilized on cariprazine: if the current dose is 1.5 or 3 mg once daily, change cariprazine to 1.5 mg orally every other day upon starting the inhibitor. If the current dose is 4.5 or 6 mg once daily, change cariprazine to 1.5 mg orally once daily upon starting the inhibitor. Once the moderate CYP3A4 inhibitor is 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
This is manageable with dose adjustment and monitoring. Because crizotinib can raise cariprazine levels, your care team will individualize your cariprazine dose based on your situation.
- Keep taking both medicines exactly as prescribed unless your team tells you otherwise.
- If you already take cariprazine and are starting crizotinib, your prescriber may lower your cariprazine dose (for example, taking it less often).
- If crizotinib is later stopped, your cariprazine dose may need to be raised again.
- Watch for and report restlessness, tremor, muscle stiffness, or unusual drowsiness.
Ask your pharmacist or prescriber to confirm the right dose for you.
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 over 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 receiving 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 unchanged by coadministration with erythromycin 2.
Common questions
Can I take Cariprazine and Crizotinib together?
Crizotinib can raise cariprazine levels and side effects, so your cariprazine dose likely needs to be lowered and monitored. Keep taking both as prescribed and confirm the correct dose with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cariprazine and Crizotinib 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 Crizotinib interaction managed?
This is manageable with dose adjustment and monitoring. Because crizotinib can raise cariprazine levels, your care team will individualize your cariprazine dose based on your situation. Keep taking both medicines exactly as prescribed unless your team tells you otherwise. If you already take cariprazine and are starting crizotinib, your prescriber may lower your cariprazine dose (for example, taki… 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 Crizotinib 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
Keep reading about Crizotinib
Keep reading about Cariprazine
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