What is the recommended dosing for Vraylar (cariprazine)?

Vraylar (Cariprazine) Dosing

The recommended starting dose of Vraylar is 1.5 mg orally once daily, with dosing adjustments based on the specific indication: for schizophrenia and bipolar mania the dose can be increased to 3 mg on Day 2 and titrated up to a maximum of 6 mg daily, while for bipolar depression and major depressive disorder (as adjunctive therapy) the maximum dose is 3 mg daily with increases only after Day 15. 1

Dosing by Indication

Schizophrenia

• Starting dose: 1.5 mg orally once daily 1
• Day 2: Can increase to 3 mg once daily 1
• Titration: Further adjustments in 1.5 mg or 3 mg increments based on clinical response and tolerability 1
• Recommended range: 1.5 mg to 6 mg once daily 1
• Maximum dose: 6 mg once daily 1
• The starting dose of 1.5 mg/day is potentially therapeutic and may not require immediate titration 2

Bipolar I Disorder - Manic or Mixed Episodes

• Starting dose: 1.5 mg orally once daily 1
• Day 2: Increase to 3 mg once daily 1
• Titration: Further adjustments in 1.5 mg or 3 mg increments 1
• Recommended range: 3 mg to 6 mg once daily 1
• Maximum dose: 6 mg once daily 1

Bipolar I Disorder - Depressive Episodes

• Starting dose: 1.5 mg orally once daily 1
• Titration: Can increase to 3 mg once daily on Day 15 based on response 1
• Maximum dose: 3 mg once daily 1
• Response rates at approved doses (1.5 and 3.0 mg/day pooled) show 46.3% vs 35.9% for placebo (NNT 10) 3

Major Depressive Disorder (Adjunctive Therapy)

• Starting dose: 1.5 mg orally once daily 1
• Titration: Can increase to 3 mg once daily on Day 15 1
• Maximum dose: 3 mg once daily 1
• Critical timing: Titration intervals of less than 14 days resulted in higher incidence of adverse reactions in clinical trials 1

Administration Details

• Frequency: Once daily 1
• Food: Can be taken with or without food 1
• Monitoring duration: Monitor patients for adverse reactions and treatment response for several weeks after starting and after each dosage change due to long half-life of cariprazine and its active metabolites 1

Dosage Modifications for Drug Interactions

With Strong CYP3A4 Inhibitors

• Schizophrenia: Start at 1.5 mg every 3 days; increase to 1.5 mg every other day if needed 1
• Bipolar mania/depression/MDD adjunct: 1.5 mg every 3 days 1
• If already on stable dose (1.5-3 mg): Reduce to 1.5 mg every 3 days 1
• If already on stable dose (4.5-6 mg): Reduce to 1.5 mg every other day 1

With Moderate CYP3A4 Inhibitors

• Schizophrenia: Start at 1.5 mg every other day; increase to 1.5 mg daily if needed 1
• Bipolar mania/depression/MDD adjunct: 1.5 mg every other day 1
• If already on stable dose (1.5-3 mg): Reduce to 1.5 mg every other day 1
• If already on stable dose (4.5-6 mg): Reduce to 1.5 mg daily 1

Important Clinical Considerations

Pharmacokinetic profile: Cariprazine has a long half-life, and its principal active metabolite didesmethyl-cariprazine (DDCAR) has a half-life of 1-3 weeks; at steady state DDCAR is the predominant circulating moiety 3. This means changes in dose will not be fully reflected in plasma for several weeks 1.

Efficacy ceiling: Dosages above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions for schizophrenia and bipolar mania 1.

Common adverse events: The most common adverse events (≥5% and at least twice the rate of placebo) are extrapyramidal symptoms (NNH 15 for 1.5-3 mg/day, NNH 10 for 4.5-6 mg/day) and akathisia (NNH 20 for 1.5-3 mg/day, NNH 12 for 4.5-6 mg/day) 2.