Look for bipolar I that may be hidden beneath symptoms of depression

1 in 4 patients being treated for depression in a primary care setting actually has bipolar disorder2

Patients are less likely to appear in your office when predominantly manic2

Patients report spending three times longer in a depressed mood state than mania3

Take 5 minutes to screen depressed patients for manic symptoms

The Mood Disorder Questionnaire (MDQ) is a 3-question form that uses patient-reported answers to help identify bipolar I disorder

No matter the bipolar I episode, VRAYLAR is approved to treat it1

In a long-term follow-up study, patients spent 47% of weeks symptomatic and 53% asymptomatic.3

VRAYLAR is proven to treat the depressive, manic, and mixed episodes of bipolar I disorder.1

The approval of VRAYLAR for the treatment of bipolar depression and manic and mixed episodes was based on the change from baseline in total score, not individual symptom measurement, on the MADRS and the YMRS, respectively.1

*Mixed bipolar I is clinically defined by DSM as Mixed features (DSM-5): Manic episode + 3 or more depressive symptoms lasting ≥1 week or major depressive episode + 3 or more manic symptoms lasting ≥2 weeks; Mixed episode (DSM-IV-TR): Manic episode lasting ≥1 week + major depressive episode.8,10

DSM=Diagnostic and Statistical Manual of Mental Disorders; MADRS=Montgomery-Asberg Depression Rating Scale; YMRS=Young Mania Rating Scale.

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 dementia-related psychosis.
  • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all 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 hypersensitivity. Reactions have included rash, pruritus, urticaria, and events suggestive of angioedema.

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic 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, 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 events 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 have caused metabolic changes, such as:

  • Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with 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 soon 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 baseline and frequently thereafter.

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 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: In clinical trials, the most common adverse reactions (≥5% and at least twice the rate of placebo) are listed below:

  • Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5 – 3 mg/day and 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 mg/day vs placebo) were: EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%).

  • Bipolar depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were: nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (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.

IMPORTANT SAFETY INFORMATION

More Less

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 dementia-related psychosis.
  • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all 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 hypersensitivity. Reactions have included rash, pruritus, urticaria, and events suggestive of angioedema.

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials with antipsychotic 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, 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 events 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 have caused metabolic changes, such as:

  • Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases associated with ketoacidosis, hyperosmolar coma, or death, has been reported in patients treated with 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 soon 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 baseline and frequently thereafter.

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 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: In clinical trials, the most common adverse reactions (≥5% and at least twice the rate of placebo) are listed below:

  • Schizophrenia: The incidences within the recommended dose range (VRAYLAR 1.5 – 3 mg/day and 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 mg/day vs placebo) were: EPS (26% vs 12%), akathisia (20% vs 5%), vomiting (10% vs 4%), dyspepsia (7% vs 4%), somnolence (7% vs 4%), and restlessness (7% vs 2%).

  • Bipolar depression: The incidences within the recommended doses (VRAYLAR 1.5 mg/day or 3 mg/day vs placebo) were: nausea (7%, 7% vs 3%), akathisia (6%, 10% vs 2%), restlessness (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.