IMPORTANT SAFETY INFORMATION
WARNINGS: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and
SUICIDAL THOUGHTS AND BEHAVIORS
- Elderly patients with dementia-related psychosis treated with antipsychotic drugs
are at an
increased risk of death. VRAYLAR is not approved for treatment of patients with
- Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Safety and effectiveness of VRAYLAR have not been established in pediatric patients.
Contraindication: VRAYLAR is contraindicated in patients with known
Reactions have included rash, pruritus, urticaria, and events suggestive of angioedema.
Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with
drugs, elderly subjects 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,
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
involuntary, dyskinetic movements) and the likelihood it will become irreversible may
increase with the duration of treatment and the cumulative dose. The syndrome can
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
Late-Occurring Adverse Reactions: Adverse events may first appear several
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
reactions, including extrapyramidal symptoms (EPS) or akathisia, and patient response
several weeks after starting VRAYLAR and after each dosage increase. Consider reducing
dose or discontinuing the drug.
Metabolic Changes: Atypical antipsychotics have caused metabolic changes,
- Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases
ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated
atypical antipsychotics. Assess fasting glucose before or soon after initiation of
treatment, and monitor periodically during long-term treatment.
- Dyslipidemia: Atypical antipsychotics cause adverse alterations in
lipids. Before or
after starting an antipsychotic, obtain baseline fasting lipid profile and monitor
periodically during treatment.
- Weight Gain: Weight gain has been observed with VRAYLAR. Monitor weight at
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia have
antipsychotics, including VRAYLAR. Agranulocytosis (including fatal cases) has been
with other antipsychotics. Monitor complete blood count in patients with pre-existing
white blood cell count (WBC)/absolute neutrophil count or history of drug-induced
leukopenia/neutropenia. Discontinue VRAYLAR at the first sign of a clinically
decline in WBC and in severely neutropenic patients.
Orthostatic Hypotension and Syncope: Atypical antipsychotics cause
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
Falls: VRAYLAR may cause somnolence, postural hypotension, motor and sensory
which may lead to falls and, consequently, fractures, or other injuries. For patients
diseases, conditions, or medications that could exacerbate these effects, complete fall
assessments when initiating antipsychotics and recurrently for patients on long-term
Seizures: Use VRAYLAR with caution in patients with history of seizures or
that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: Somnolence was reported with
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
conditions that increase body temperature (eg, strenuous exercise, extreme heat,
dehydration, or concomitant anticholinergics).
Dysphagia: Esophageal dysmotility and aspiration have been associated with
Antipsychotic drugs, including VRAYLAR, should be used cautiously in patients at risk
Drug Interactions: Strong CYP3A4 inhibitors increase VRAYLAR concentrations,
reduction is recommended. Concomitant use with CYP3A4 inducers is not recommended.
Adverse Reactions: In clinical trials, the most common adverse reactions
(≥5% and at
twice the rate of placebo) are listed below:
- Schizophrenia: The incidences within the recommended dose range
(VRAYLAR 1.5 – 3
4.5 – 6 mg/day vs placebo) were: EPS (15%, 19% vs 8%) and akathisia (9%, 13% vs 4%).
- Bipolar mania: The incidences within the recommended dose range
(VRAYLAR 3 – 6
placebo) were: EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%),
vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%).
- Bipolar depression: The incidences within the recommended doses
(VRAYLAR 1.5 mg/day
mg/day vs placebo) were: nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%),
7% vs 3%), and EPS (4%, 6% vs 2%).
INDICATIONS AND USAGE
VRAYLAR (cariprazine) is indicated in adults for the treatment of depressive episodes
associated with bipolar I disorder (bipolar depression), the acute treatment of manic or
mixed episodes associated with bipolar I disorder, and the treatment of schizophrenia.
Please also see full Prescribing
Information, including Boxed Warnings.