Vraylar (Cariprazine) Titration Schedule
The recommended titration schedule for Vraylar (cariprazine) begins with 1.5 mg orally once daily, with gradual increases based on indication, clinical response, and tolerability. 1
General Titration Principles
- Vraylar is administered orally once daily and can be taken with or without food 1
- Due to the long half-life of cariprazine and its active metabolites, changes in dose will not be fully reflected in plasma for several weeks 1
- Monitoring for adverse reactions and treatment response should continue for several weeks after starting Vraylar and after each dosage change 1
Indication-Specific Titration Schedules
Schizophrenia
- Starting dose: 1.5 mg orally once daily 1
- Can increase to 3 mg on Day 2 1
- Further dose adjustments can be made in 1.5 mg or 3 mg increments based on response and tolerability 1
- Recommended dose range: 1.5-6 mg orally once daily 1
- Maximum recommended dose: 6 mg once daily 1
Bipolar I Disorder (Manic or Mixed Episodes)
- Starting dose: 1.5 mg orally once daily 1
- Increase to 3 mg orally once daily on Day 2 1
- Further dose adjustments can be made in 1.5 mg or 3 mg increments based on response and tolerability 1
- Recommended dose range: 3-6 mg orally once daily 1
- Maximum recommended dose: 6 mg once daily 1
Bipolar I Disorder (Depressive Episodes)
- Starting dose: 1.5 mg orally once daily 1
- Can increase to 3 mg orally once daily on Day 15 based on clinical response and tolerability 1
- Maximum recommended dose: 3 mg once daily 1
Major Depressive Disorder (Adjunctive Therapy)
- Starting dose: 1.5 mg orally once daily 1
- Can increase to 3 mg orally once daily on Day 15 based on clinical response and tolerability 1
- Maximum recommended dose: 3 mg once daily 1
- In clinical trials, titration at intervals less than 14 days resulted in higher incidence of adverse reactions 1
Special Dosing Considerations
When Taking CYP3A4 Inhibitors
- Strong CYP3A4 inhibitors: Start at 1.5 mg every 3 days for schizophrenia and bipolar mania; can increase to 1.5 mg every other day if needed 1
- Moderate CYP3A4 inhibitors: Start at 1.5 mg every other day for schizophrenia and bipolar mania; can increase to 1.5 mg daily if needed 1
- For bipolar depression and adjunctive MDD therapy: 1.5 mg every 3 days with strong inhibitors; 1.5 mg every other day with moderate inhibitors 1
Dose Modifications When Adding CYP3A4 Inhibitors to Stable Vraylar Treatment
- For patients on 1.5 or 3 mg daily: Reduce to 1.5 mg every 3 days with strong inhibitors or 1.5 mg every other day with moderate inhibitors 1
- For patients on 4.5 or 6 mg daily: Reduce to 1.5 mg every other day with strong inhibitors or 1.5 mg once daily with moderate inhibitors 1
Important Clinical Considerations
- Dosages above 6 mg daily do not provide increased effectiveness sufficient to outweigh dose-related adverse reactions 1
- Common adverse effects include akathisia, insomnia, and extrapyramidal symptoms 2
- Cariprazine has a unique pharmacokinetic profile with active metabolites that have very long half-lives (1-3 weeks for didesmethyl-cariprazine) 3, 4
- After discontinuation, plasma concentrations decline by 50% in approximately 1 week 1
- In real-world settings, cariprazine has shown minimal impact on weight gain, BMI, and blood pressure when evaluated up to 12 months 5
Monitoring Recommendations
- Monitor patients for adverse reactions and treatment response for several weeks after starting Vraylar and after each dosage change 1
- Be aware that due to the long half-life, adverse effects may persist even after dose reduction 1, 4
- Pay particular attention to extrapyramidal symptoms and akathisia, which are among the most common side effects 2, 6