Vraylar (Cariprazine) Dosing
For schizophrenia, start Vraylar at 1.5 mg once daily and titrate to a target range of 1.5-6 mg daily; for bipolar mania, start at 1.5 mg and increase to 3 mg on Day 2 with a target range of 3-6 mg daily; for bipolar depression and adjunctive treatment of major depressive disorder, start at 1.5 mg daily with a maximum of 3 mg daily, increasing no sooner than Day 15. 1
Schizophrenia Dosing
- Starting dose: 1.5 mg orally once daily 1
- Day 2 option: May increase to 3 mg if clinically indicated 1
- Target range: 1.5-6 mg once daily 1
- Dose adjustments: Can be made in 1.5 mg or 3 mg increments based on clinical response and tolerability 1
- Maximum dose: 6 mg once daily—doses above 6 mg do not provide additional benefit but increase adverse reactions 1
The recommended dose range for schizophrenia is 1.5-6 mg/day, with the 1.5 mg starting dose being potentially therapeutic 2. In clinical trials, pooled responder rates were 31% for cariprazine 1.5-6 mg/day versus 21% for placebo, yielding a number needed to treat of 10 2.
Bipolar Mania Dosing
- Starting dose: 1.5 mg once daily 1
- Day 2: Increase to 3 mg once daily 1
- Target range: 3-6 mg once daily 1
- Dose adjustments: Can be made in 1.5 mg or 3 mg increments 1
- Maximum dose: 6 mg once daily—higher doses do not confer increased effectiveness 1
Bipolar Depression Dosing
- Starting dose: 1.5 mg once daily 1
- Dose increase timing: May increase to 3 mg on Day 15 based on clinical response and tolerability 1
- Maximum dose: 3 mg once daily 1
Adjunctive Treatment for Major Depressive Disorder
- Starting dose: 1.5 mg once daily 1
- Dose increase timing: May increase to 3 mg on Day 15 if needed 1
- Maximum dose: 3 mg once daily 1
- Critical timing consideration: Titration at intervals less than 14 days resulted in higher incidence of adverse reactions in clinical trials 1
Interestingly, for adjunctive treatment in major depression, the 1.5 mg dose was significantly more effective than placebo, while the 3 mg dose showed less consistent efficacy 3.
Administration Guidelines
- Timing: Once daily, can be taken with or without food 1
- Monitoring duration: Due to the long half-life of cariprazine and its active metabolites (2-5 days for cariprazine, 2-3 weeks for didesmethyl-cariprazine), changes in dose will not be fully reflected in plasma for several weeks 1, 4
- Clinical implication: Monitor patients for adverse reactions and treatment response for several weeks after starting Vraylar and after each dosage change 1
Dosage Modifications with CYP3A4 Inhibitors
When Starting Vraylar While Taking CYP3A4 Inhibitors
Strong CYP3A4 inhibitors:
- Schizophrenia: Start at 1.5 mg every 3 days; may increase to 1.5 mg every other day if needed 1
- Bipolar mania, bipolar depression, adjunctive MDD: 1.5 mg every 3 days 1
Moderate CYP3A4 inhibitors:
- Schizophrenia: Start at 1.5 mg every other day; may increase to 1.5 mg daily if needed 1
- Bipolar mania, bipolar depression, adjunctive MDD: 1.5 mg every other day 1
When Adding CYP3A4 Inhibitors to Stable Vraylar Dose
If currently on 1.5 or 3 mg daily:
- With strong inhibitor: Reduce to 1.5 mg every 3 days 1
- With moderate inhibitor: Reduce to 1.5 mg every other day 1
If currently on 4.5 or 6 mg daily:
- With strong inhibitor: Reduce to 1.5 mg every other day 1
- With moderate inhibitor: Reduce to 1.5 mg daily 1
Common Pitfalls and Clinical Considerations
Extrapyramidal symptoms and akathisia are the most common adverse events, with number needed to harm of 15 for EPS and 20 for akathisia at 1.5-3 mg/day doses 2. These rates increase at higher doses (4.5-6 mg/day: NNH 10 for EPS, NNH 12 for akathisia) 2.
Metabolic profile is favorable: Short-term weight gain is minimal (approximately 8% of patients on 1.5-6 mg/day gained ≥7% body weight versus 5% on placebo, NNH 34), with no clinically meaningful alterations in glucose, lipids, prolactin, or ECG QT interval 2, 4.
The long half-life requires patience: Because didesmethyl-cariprazine has a half-life of 2-3 weeks and achieves several times higher systemic exposure than the parent compound, full therapeutic effects and side effects may take weeks to manifest 4. This is particularly important when discontinuing—effects will persist for weeks after the last dose 4.
Contraception requirement: Cariprazine requires effective contraception in female patients of childbearing age 5.