Adagrasib and Cariprazine: 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
Adagrasib
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. Adagrasib (Krazati) blocks a liver enzyme called CYP3A4 that normally breaks down cariprazine (Vraylar). When that enzyme is slowed down, cariprazine and its active byproduct can build up in your body, roughly doubling your exposure. That can mean stronger side effects, like restlessness, trouble sleeping, or movement problems.
The good news is that this is very manageable. Your care team knows about this and can simply use a lower or less frequent cariprazine dose while you are on adagrasib. Please keep taking both medicines as prescribed and let your pharmacist or doctor know you are on both so they can tailor the dose for you.
Effect: Adagrasib is a strong CYP3A4 inhibitor; cariprazine is a CYP3A4 substrate. Coadministration reduces cariprazine clearance, increasing exposure to cariprazine and its active metabolite didesmethylcariprazine. The ketoconazole probe study showed roughly a 100% increase in AUC and Cmax.
Direction: increased cariprazine effect. Evidence: probable. Onset: unspecified.
Management (per labeling):
- Initiation for schizophrenia/bipolar mania: 1.5 mg every 3 days, may increase to 1.5 mg every other day per response.
- Bipolar depression or adjunct MDD: 1.5 mg every 3 days.
- Stable 1.5 or 3 mg daily: reduce to 1.5 mg every 3 days.
- Stable 4.5 or 6 mg daily: reduce to 1.5 mg every other day.
- On inhibitor discontinuation, dose may need increasing.
Monitor for EPS, akathisia, sedation.
What happens
Increased exposure to cariprazine and its active metabolite, didesmethylcariprazine
Interaction Deep Dive
Taking cariprazine (which is metabolized by CYP3A4) together with a potent CYP3A4 inhibitor can raise the exposure of cariprazine as well as its active metabolite, didesmethylcariprazine. In drug interaction trials, giving cariprazine alongside ketoconazole (a strong CYP3A4 inhibitor) produced roughly a 100% rise in both AUC and Cmax. Consequently, for patients beginning cariprazine while on a strong CYP3A4 inhibitor (in schizophrenia or bipolar mania), the starting dose should be 1.5 mg orally every 3 days, with a possible increase to 1.5 mg orally every other day if warranted by clinical response and tolerability. For those on a strong CYP3A4 inhibitor being treated for bipolar depression or receiving adjunctive therapy for MDD, the dose is 1.5 mg orally every 3 days. If a strong CYP3A4 inhibitor is being added to an already stable cariprazine regimen, the cariprazine dose must be modified: patients taking 1.5 or 3 mg once daily should be switched to 1.5 mg orally every 3 days upon starting the inhibitor, whereas those taking 4.5 or 6 mg once daily should be moved to 1.5 mg orally every other day. Once the strong CYP3A4 inhibitor is stopped, the cariprazine dose may require an increase guided by clinical response and tolerability1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of cariprazine
How to manage this interaction
This interaction is well recognized and your care team can manage it by adjusting your cariprazine dose while you are taking adagrasib.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your team may lower your cariprazine dose or space it out further (for example, taking it less often) because adagrasib raises cariprazine levels.
- If adagrasib is later stopped, your cariprazine dose may need to be increased again based on how you respond.
- Watch for and report restlessness, muscle stiffness or tremor, unusual movements, drowsiness, or trouble sleeping.
Tell your pharmacist and prescriber you are on both so they can individualize your dose and monitor 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 0.5 mg/day together with ketoconazole 400 mg/day led to an increase in total cariprazine AUC and Cmax of roughly 100% 1.
Common questions
Can I take Adagrasib and Cariprazine together?
Adagrasib raises cariprazine levels by blocking CYP3A4, so your care team will likely lower or space out your cariprazine dose while you are on adagrasib and watch for extra side effects. Keep taking both as prescribed and confirm the right dose with your prescriber. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Adagrasib and Cariprazine 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 Adagrasib and Cariprazine interaction managed?
This interaction is well recognized and your care team can manage it by adjusting your cariprazine dose while you are taking adagrasib. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your team may lower your cariprazine dose or space it out further (for example, taking it less often) because adagrasib raises cariprazine levels. If adagrasib is later stopped, you… 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 Adagrasib or Cariprazine 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: VRAYLAR(R) oral capsules, cariprazine oral capsules. AbbVie Inc. (per FDA), North Chicago, IL, 2024. DailyMed
Keep reading about Adagrasib
Keep reading about Cariprazine
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