What is the recommended dosing for Vraylar (cariprazine) in adult patients with schizophrenia or bipolar disorder, particularly in those with impaired renal or hepatic function?

Vraylar (Cariprazine) Dosing

Schizophrenia

Start Vraylar at 1.5 mg orally once daily, which can be increased to 3 mg on Day 2, with further adjustments in 1.5 mg or 3 mg increments based on response and tolerability, up to a maximum of 6 mg daily. 1

• The recommended dosage range is 1.5 mg to 6 mg orally once daily 1
• Doses above 6 mg daily do not provide increased effectiveness sufficient to outweigh dose-related adverse reactions 1
• Vraylar can be taken with or without food 1

Bipolar I Disorder - Manic or Mixed Episodes

Start Vraylar at 1.5 mg orally once daily, then increase to 3 mg on Day 2, with the recommended dosage range being 3 mg to 6 mg daily, and a maximum of 6 mg daily. 1

• Further dose adjustments can be made in 1.5 mg or 3 mg increments depending on clinical response and tolerability 1
• Doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions 1

Bipolar I Disorder - Depressive Episodes (Bipolar Depression)

Start Vraylar at 1.5 mg orally once daily, with the option to increase to 3 mg on Day 15 based on response and tolerability, with a maximum recommended dose of 3 mg daily. 1

• This indication requires a lower maximum dose (3 mg) compared to schizophrenia or bipolar mania 1

Major Depressive Disorder (Adjunctive Therapy)

Start Vraylar at 1.5 mg orally once daily as adjunctive therapy to antidepressants, with the option to increase to 3 mg on Day 15, and a maximum recommended dose of 3 mg daily. 1

• Dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions in clinical trials 1
• Wait at least 14 days before increasing the dose 1

Critical Dosing Considerations

Long Half-Life and Monitoring

Monitor patients for adverse reactions and treatment response for several weeks after starting Vraylar and after each dosage change, because changes in dose will not be fully reflected in plasma for several weeks due to the long half-life of cariprazine and its active metabolites. 1

• Cariprazine has a half-life of 2-4 days, with an active metabolite that has a terminal half-life of 2-3 weeks 2
• Following discontinuation, plasma concentrations will decline by 50% in approximately 1 week 1

Dosage Modifications with CYP3A4 Inhibitors

When initiating Vraylar in patients taking a strong CYP3A4 inhibitor, start at 1.5 mg every 3 days for schizophrenia (can increase to 1.5 mg every other day if needed), or 1.5 mg every 3 days for bipolar mania, bipolar depression, or MDD adjunctive therapy. 1

• With moderate CYP3A4 inhibitors, start at 1.5 mg every other day for schizophrenia (can increase to 1.5 mg daily if needed), or 1.5 mg every other day for other indications 1

For patients already on stable Vraylar doses who initiate a strong CYP3A4 inhibitor:

• If on 1.5 or 3 mg daily: reduce to 1.5 mg every 3 days 1
• If on 4.5 or 6 mg daily: reduce to 1.5 mg every other day 1

For patients already on stable Vraylar doses who initiate a moderate CYP3A4 inhibitor:

• If on 1.5 or 3 mg daily: reduce to 1.5 mg every other day 1
• If on 4.5 or 6 mg daily: reduce to 1.5 mg once daily 1

CYP3A4 Inducers

Concomitant use of Vraylar with CYP3A4 inducers has not been evaluated and is not recommended. 1

Renal and Hepatic Impairment

Vraylar should not be given to patients with severe hepatic or renal disease. 3

• The FDA label does not provide specific dosing adjustments for mild to moderate renal or hepatic impairment, but caution is advised 1

Common Pitfalls to Avoid

• Do not titrate doses faster than recommended: In MDD adjunctive therapy, titration at intervals less than 14 days resulted in higher adverse reaction rates 1
• Do not exceed 6 mg daily for schizophrenia or bipolar mania: Higher doses do not improve efficacy but increase adverse effects 1
• Do not exceed 3 mg daily for bipolar depression or MDD adjunctive therapy: These indications have lower maximum effective doses 1
• Do not forget to adjust for drug interactions: CYP3A4 inhibitors significantly increase cariprazine exposure and require substantial dose reductions 1

Safety Profile

The most commonly encountered adverse events with cariprazine include akathisia, extrapyramidal symptoms, nausea, and constipation, with a favorable metabolic profile showing minimal weight gain and no clinically meaningful alterations in glucose, lipids, or ECG QTc interval. 3, 4

• Cariprazine shows highest affinity toward D3 receptors, followed by D2, 5-HT2B, and 5-HT1A receptors 2
• Network meta-analysis demonstrates efficacy across the psychosis spectrum, with higher improvements at increasing dosages 4