Nefazodone 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
Nefazodone
No brand names on recordCariprazine
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.
Nefazodone can make cariprazine (Vraylar) build up in your body. Nefazodone strongly blocks a liver enzyme (called CYP3A4) that normally helps break down cariprazine. When that enzyme is slowed, both cariprazine and its long-lasting active form stick around longer. In studies with a similar strong blocker, blood levels roughly doubled.
Higher levels can mean more side effects, like restlessness, tremor, sleepiness, or feeling dizzy. The good news is that this is very manageable. Your care team can simply use a lower cariprazine dose while you are on nefazodone and watch how you feel. Please don't change either medicine on your own, just talk with your pharmacist or doctor.
Mechanism: Nefazodone is a strong CYP3A4 inhibitor; cariprazine is a CYP3A4 substrate (neither is a prodrug). Inhibition reduces clearance, increasing exposure to cariprazine and its active metabolite didesmethylcariprazine.
Magnitude: A strong inhibitor (ketoconazole) raised AUC and Cmax by roughly 100%. Evidence: probable. Severity: major.
Management (per labeling):
- Initiating cariprazine on a strong 3A4 inhibitor (schizophrenia/bipolar mania): 1.5 mg every 3 days, may increase to 1.5 mg every other day per response/tolerability.
- Bipolar depression or adjunctive MDD: 1.5 mg every 3 days.
- Adding inhibitor to stable cariprazine: if on 1.5 or 3 mg daily, reduce to 1.5 mg every 3 days; if on 4.5 or 6 mg daily, reduce to 1.5 mg every other day.
- On inhibitor discontinuation, cariprazine dose may need to be increased.
Monitor for dopaminergic adverse effects (akathisia, EPS, sedation).
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 exposure of cariprazine as well as its active metabolite didesmethylcariprazine can rise. In drug interaction trials, giving cariprazine alongside ketoconazole (a strong CYP3A4 inhibitor) produced roughly a 100% rise in both AUC and Cmax. For this reason, if cariprazine therapy is being started in a patient already receiving a strong CYP3A4 inhibitor (for schizophrenia or bipolar mania), begin dosing at 1.5 mg orally every 3 days, and if necessary, based on clinical response and tolerability, raise to 1.5 mg orally every other day. If a strong CYP3A4 inhibitor is present while treating bipolar depression or when cariprazine is used as adjunctive therapy for MDD, dose at 1.5 mg orally every 3 days. If a strong CYP3A4 inhibitor is introduced in a patient already on a stable cariprazine regimen, the following adjustments apply: 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. Once the strong CYP3A4 inhibitor is stopped, an increase in the cariprazine dose may be warranted according to clinical response and tolerability1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of cariprazine
How to manage this interaction
This combination is manageable, and your care team has clear dosing steps to keep cariprazine at a safe level while you take nefazodone.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your team may lower your cariprazine dose or space it out (for example, taking it every 3 days or every other day) while you are on nefazodone.
- Expect closer monitoring for side effects such as restlessness, tremor, muscle stiffness, drowsiness, or dizziness.
- If nefazodone is later stopped, your cariprazine dose may need to be raised again based on how you respond.
Ask your pharmacist or doctor to confirm the exact cariprazine dose that fits your situation and diagnosis.
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 increased the total cariprazine AUC and Cmax by roughly 100% 1.
Common questions
Can I take Nefazodone and Cariprazine together?
Nefazodone blocks the enzyme that clears cariprazine, so cariprazine levels can roughly double. Your care team will lower or space out your cariprazine dose and monitor you, so keep both as prescribed and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nefazodone 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 Nefazodone and Cariprazine interaction managed?
This combination is manageable, and your care team has clear dosing steps to keep cariprazine at a safe level while you take nefazodone. Keep taking both as prescribed unless your prescriber tells you otherwise. Your team may lower your cariprazine dose or space it out (for example, taking it every 3 days or every other day) while you are on nefazodone. Expect closer monitoring for side effects su… 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 Nefazodone 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 Nefazodone
Keep reading about Cariprazine
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