Idelalisib 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
Idelalisib
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.
You've been prescribed idelalisib (Zydelig) and cariprazine (Vraylar). Here's what's going on: your body clears cariprazine using a liver enzyme called CYP3A4. Idelalisib strongly blocks that enzyme, so cariprazine and its long-lasting active form can build up higher than usual. In studies with a similar strong blocker, levels roughly doubled.
More cariprazine in your system can mean stronger side effects, like restlessness, tremor, drowsiness, or trouble with movement. The good news is this is very manageable. Your care team can simply use a lower, spaced-out cariprazine dose while you're on idelalisib and watch how you feel. Don't change anything on your own, just keep taking both and check in with your doctor or pharmacist.
Effect: Idelalisib is a strong CYP3A4 inhibitor; cariprazine is a CYP3A4 substrate (active metabolite didesmethylcariprazine). Coadministration raises exposure to both. Ketoconazole data showed ~100% increase in AUC and Cmax.
Direction: Increased cariprazine effect/toxicity risk (EPS, akathisia, sedation). Evidence: probable. Onset: unspecified.
Management (per labeling):
- New start with a strong inhibitor: schizophrenia/bipolar mania 1.5 mg every 3 days, may increase to 1.5 mg every other day per response; bipolar depression/MDD adjunct 1.5 mg every 3 days.
- On stable 1.5 or 3 mg daily then adding inhibitor: switch to 1.5 mg every 3 days.
- On 4.5 or 6 mg daily: switch to 1.5 mg every other day.
- When inhibitor stops, dose may need to be increased per response.
What happens
Increased exposure to cariprazine and its active metabolite, didesmethylcariprazine
Interaction Deep Dive
When cariprazine (a CYP3A4 substrate) is given together with a potent CYP3A4 inhibitor, the levels of both cariprazine and its active metabolite, didesmethylcariprazine, may rise. In drug interaction trials, combining cariprazine with ketoconazole (a strong CYP3A4 inhibitor) produced an AUC and Cmax increase of roughly 100%. For this reason, when cariprazine is being started in a patient already receiving a strong CYP3A4 inhibitor (for schizophrenia or bipolar mania), begin with 1.5 mg orally every 3 days, and if warranted by clinical response and tolerability, titrate up to 1.5 mg orally every other day. In patients 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 introduced in someone already on a stable cariprazine regimen: for those currently taking 1.5 or 3 mg once daily, change the cariprazine dose to 1.5 mg orally every 3 days upon starting the inhibitor; for those currently taking 4.5 or 6 mg once daily, change the cariprazine dose to 1.5 mg orally every other day upon starting the inhibitor. Should the strong CYP3A4 inhibitor be stopped, an increase in the cariprazine dose may be required, guided by clinical response and tolerability1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of cariprazine
How to manage this interaction
Keep taking both medicines as prescribed and do not adjust doses yourself. Because idelalisib slows how you break down cariprazine, your team will typically lower and space out your cariprazine dose while you are on idelalisib, then re-adjust it if idelalisib is stopped. The exact schedule is individualized by your prescriber based on your current dose and how you respond.
- Tell your pharmacist and doctor that you take both drugs.
- Report new or worsening restlessness, tremor, stiffness, uncontrolled movements, or heavy drowsiness.
- Ask before starting or stopping either medication so your cariprazine dose can be reviewed.
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 approximately 100% 1.
Common questions
Can I take Idelalisib and Cariprazine together?
Idelalisib can roughly double cariprazine levels by blocking CYP3A4, so your care team will lower and space out your cariprazine dose while you take both and readjust it if idelalisib is stopped. Keep taking both as prescribed and report any restlessness, tremor, stiffness, or drowsiness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Idelalisib 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 Idelalisib and Cariprazine interaction managed?
Keep taking both medicines as prescribed and do not adjust doses yourself. Because idelalisib slows how you break down cariprazine, your team will typically lower and space out your cariprazine dose while you are on idelalisib, then re-adjust it if idelalisib is stopped. The exact schedule is individualized by your prescriber based on your current dose and how you respond. Tell your pharmacist and… 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 Idelalisib 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 Idelalisib
Keep reading about Cariprazine
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