No matter the bipolar I episode (depressive, acute manic or mixed), VRAYLAR is approved to treat it1
It is unknown if the statistically significant differences observed at time points earlier than Week 3 represent clinically relevant treatment effects.
Maximum recommended dose of VRAYLAR is 6 mg/day. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed.1
Three 3-week, randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of VRAYLAR in adult patients (18-65 years old) with manic or mixed episodes of bipolar I disorder, with or without psychotic features, based on DSM-IV-TR criteria. The primary statistical analyses were conducted using an MMRM approach for Study 4 and Study 6 and the LOCF approach for Study 5. In each study, the primary endpoint was the LS mean change from baseline in YMRS total score at the end of Week 3.1,9-11
DSM=Diagnostic and Statistical Manual of Mental Disorders; LOCF=last observation carried forward; LS=least squares; MMRM=mixed-effects model for repeated measures; TR=text revision; YMRS=Young Mania Rating Scale.
The analyses were not prespecified endpoints and were not adjusted for multiplicity. Therefore, treatment differences cannot be regarded as statistically significant.
VRAYLAR was approved based on the primary endpoint, mean change in YMRS total score from baseline at Week 3.1
Maximum recommended dose of VRAYLAR is 6 mg/day. Doses above 6 mg daily did not appear to have additional benefit over lower doses and a dose-related increase in certain adverse reactions was observed.1
A post-hoc analysis of data pooled from 3 similarly designed, randomized, placebo-controlled, double-blind, multicenter, parallel-group studies of adult patients with bipolar I disorder. Patients in the ITT population (N=1037) were treated with either placebo (n=429) or VRAYLAR (n=608). VRAYLAR doses 3–12 mg/day were pooled for analysis. Mean change from baseline at 3 weeks on individual YMRS items was analyzed using an MMRM approach.12
ITT= intent-to-treat.
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
