Recommended Dosage and Treatment Guidelines for Vraylar (Cariprazine)
For schizophrenia and bipolar disorder, Vraylar (cariprazine) should be started at 1.5 mg once daily, with a recommended dosage range of 1.5-6 mg daily for schizophrenia and 3-6 mg daily for bipolar mania, while bipolar depression requires a maximum of 3 mg daily. 1
Dosage Recommendations by Indication
Schizophrenia
- Starting dose: 1.5 mg once daily
- Day 2: Can increase to 3 mg once daily
- Recommended range: 1.5-6 mg once daily
- Maximum dose: 6 mg daily (higher doses increase adverse reactions without additional benefit) 1
- Further dose adjustments can be made in 1.5 mg or 3 mg increments based on response and tolerability
Bipolar I Disorder - Manic or Mixed Episodes
- Starting dose: 1.5 mg once daily
- Day 2: Increase to 3 mg once daily
- Recommended range: 3-6 mg once daily
- Maximum dose: 6 mg daily 1
- Further dose adjustments can be made in 1.5 mg or 3 mg increments based on response and tolerability
Bipolar I Disorder - Depressive Episodes
- Starting dose: 1.5 mg once daily
- Can increase to 3 mg once daily on Day 15 based on response and tolerability
- Maximum dose: 3 mg once daily 1
Administration Guidelines
- Administer once daily with or without food 1
- Due to cariprazine's long half-life and active metabolites, changes in dose will not be fully reflected in plasma for several weeks 1, 2
- Monitor patients for adverse reactions and treatment response for several weeks after starting cariprazine and after each dosage change 1
Special Dosing Considerations
Drug Interactions
When taking strong CYP3A4 inhibitors:
- For schizophrenia: Start at 1.5 mg every 3 days
- For bipolar disorders: 1.5 mg every 3 days 1
When taking moderate CYP3A4 inhibitors:
- For schizophrenia: Start at 1.5 mg every other day
- For bipolar disorders: 1.5 mg every other day 1
Concomitant use with CYP3A4 inducers is not recommended 1
Pharmacological Profile
- Cariprazine is a dopamine D3 and D2 receptor partial agonist with higher affinity for D3 receptors 2
- Also acts as a partial agonist at serotonin 5-HT1A receptors and antagonist at 5-HT2B and 5-HT2A receptors 2
- Has two active metabolites: desmethyl-cariprazine and didesmethyl-cariprazine, with the latter having a substantially longer half-life (2-3 weeks) 2, 3
Efficacy and Treatment Duration
- For schizophrenia, antipsychotic treatment should be continued for at least 12 months after beginning remission 4
- In bipolar disorder, maintenance treatment with mood stabilizers should continue for at least 2 years after the last episode 4
- In clinical trials, cariprazine showed superiority over placebo in reducing positive and negative symptoms of schizophrenia at doses of 1.5-6 mg/day 2
Common Adverse Events
- Most common adverse events (≥5% and at least twice the rate of placebo):
- Short-term weight gain appears small (NNH 34 for ≥7% weight gain) 2
- No clinically meaningful alterations in metabolic variables, prolactin, or ECG QT interval 2
Important Monitoring Considerations
- Monitor for extrapyramidal symptoms and akathisia, particularly at higher doses 2
- Due to the long half-life of cariprazine and its active metabolites (particularly didesmethyl-cariprazine), effects of dose changes may not be apparent for several weeks 1, 3
- Regular assessment of therapeutic response and side effects is essential throughout treatment
Treatment Approach
- Start with the recommended initial dose (1.5 mg daily)
- Titrate gradually according to indication-specific guidelines
- Monitor for response and side effects for several weeks after initiation and dose changes
- Adjust dose as needed within the recommended range
- Continue treatment for the recommended duration based on the condition being treated
Cariprazine represents a unique antipsychotic option with its D3-preferring receptor profile, potentially offering advantages for both positive and negative symptoms of schizophrenia while maintaining a favorable metabolic profile.