One Capsule1
Once Daily1
With or Without Food1
Starting Dose
Capsule images are not actual size
Adjunctive Therapy to Antidepressants for MDD Recommended Doses
Maximum recommended dose is 3 mg/day, depending on clinical response and tolerability.
In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions.1,2Prescribing Information).
(See adverse reactions from 8-week study in Section 6.1 of the fullFollowing discontinuation of VRAYLAR, the decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients’ clinical symptoms.1
Bipolar I Depression Recommended Doses
Maximum recommended dose is 3 mg/day, depending on clinical response and tolerability.
Bipolar I Acute Manic or Mixed Episodes Recommended Doses
Further adjustments can be made in 1.5- or 3-mg/day increments, up to a maximum recommended dose of 6 mg/day, depending on clinical response and tolerability.*
Schizophrenia Recommended Doses
Dose can be increased to 3 mg on Day 21
Further adjustments can be made in 1.5- or 3-mg increments, up to a maximum recommended dose of 6 mg/day, depending on clinical response and tolerability.*
No dosage adjustment required based on1:
Mild or moderate hepatic or renal impairment
Smoking status
Age
Race
Sex
VRAYLAR is not recommended in patients with severe hepatic (Child-Pugh score 10–15) or renal impairment (creatinine clearance <30 mL/min), as it has not been evaluated in these patient populations1
VRAYLAR can be coadministered with a PPI. It does not affect VRAYLAR exposure at steady state1*
Monitoring fasting plasma glucose, fasting lipid profile, and CBCs is recommended for patients on antipsychotic treatment.1
*Pantoprazole 40 mg/day was coadministered with VRAYLAR 6 mg/day in patients with schizophrenia for 15 days.1
CBC=complete blood count; PPI=proton pump inhibitor.
VRAYLAR is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6.1
CYP3A4 is responsible for the formation and elimination of the major active metabolites of cariprazine.1
Clinically significant drug interactions and dosage adjustments with VRAYLAR1
Clinical impact | Intervention |
Strong CYP3A4 inhibitors | Initiating strong CYP3A4 inhibitor while on a stable dose of VRAYLAR Reduce the current dosage of VRAYLAR by half:
Initiating VRAYLAR therapy while already on a strong CYP3A4 inhibitor
When the CYP3A4 inhibitor is withdrawn, VRAYLAR dosage may need to be increased |
CYP3A4 inducers | Not recommended |
INDICATIONS AND USAGE
VRAYLAR (cariprazine) is indicated in adults as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), for the treatment of depressive episodes associated with bipolar I disorder (bipolar depression), for the acute treatment of manic or mixed episodes associated with bipolar I disorder, and for the treatment of schizophrenia.
Contraindication: VRAYLAR is contraindicated in patients with known hypersensitivity. Reactions have included rash, pruritus, urticaria, and reactions suggestive of angioedema.
Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic drugs, elderly patients with dementia had a higher incidence of cerebrovascular adverse reactions, including fatalities, vs placebo. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with antipsychotic drugs. NMS may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage with immediate discontinuation, intensive symptomatic treatment, and monitoring.
Tardive Dyskinesia (TD): Risk of developing TD (a syndrome of potentially irreversible, involuntary, dyskinetic movements) and the likelihood it will become irreversible may increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses, or after treatment discontinuation. If signs and symptoms of TD appear, drug discontinuation should be considered.
Late-Occurring Adverse Reactions: Adverse reactions may first appear several weeks after initiation of VRAYLAR, probably because plasma levels of cariprazine and its major metabolites accumulate over time. As a result, the incidence of adverse reactions in short-term trials may not reflect the rates after longer-term exposures. Monitor for adverse reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response for several weeks after starting VRAYLAR and after each dosage increase. Consider reducing the dose or discontinuing the drug.
Metabolic Changes: Atypical antipsychotics, including VRAYLAR, have caused metabolic changes, such as:
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have been reported with antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been reported with other antipsychotics. Monitor complete blood count in patients with pre-existing low white blood cell count (WBC)/absolute neutrophil count or history of drug-induced leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically significant decline in WBC and in severely neutropenic patients.
Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope, with the greatest risk during initial titration and with dose increases. Monitor orthostatic vital signs in patients predisposed to hypotension and in those with cardiovascular/cerebrovascular diseases.
Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotics and recurrently for patients on long-term therapy.
Seizures: Use VRAYLAR with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Somnolence was reported with VRAYLAR. Caution patients about performing activities requiring mental alertness (eg, operating hazardous machinery or a motor vehicle).
Body Temperature Dysregulation: Use VRAYLAR with caution in patients who may experience conditions that increase body temperature (eg, strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics).
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk for aspiration.
Drug Interactions: Strong CYP3A4 inhibitors increase VRAYLAR concentrations, so VRAYLAR dose reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended.
Adverse Reactions: The most common adverse reactions in clinical trials ( 5% and at least twice the rate of placebo) are listed below:
US-VRA-220402