How to dose VRAYLAR for bipolar I disorder in depressive and acute manic or mixed episodes1

How to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodes

One capsule1

How to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodes

Once daily1

How to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesHow to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodes

With or without food1

Effective VRAYLAR doses
for bipolar I1

An image that shows how to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesAn image that shows how to dose VRAYLAR for bipolar disorder in depressive and acute manic or mixed episodesAn image that shows how to dose VRAYLAR for bipolar I disorder in depressive and acute manic or mixed episodes

BIPOLAR I DEPRESSION1

Recommended dose:
1.5 or 3 mg/day
  • Day 1—Start patient at 1.5 mg
  • Day 15—May increase dose to 3 mg
Maximum recommended dose is 3 mg/day, depending on clinical response and tolerability.

BIPOLAR I MANIA OR MIXED1

Recommended dose:
3–6 mg/day
  • Day 1—Start patient at 1.5 mg
  • Day 2—Increase dose to 3 mg
  • *In short-term controlled studies, doses above 6 mg/day did not confer increased effectiveness sufficient to outweigh dose-related adverse reactions.1
  • Following discontinuation of VRAYLAR, the decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients’ clinical symptoms1

No dosage adjustment required based on1:

Graphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sex

Mild or moderate hepatic or renal impairment

Graphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sex

Smoking
status

Graphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sex

Age

Graphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sex

Race

Graphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sexGraphic showing no dosage adjustment required based on listed characteristics: mild or moderate hepatic or renal impairment, smoking status, age, rage, and sex

Sex

Monitoring fasting plasma glucose, fasting lipid profile, and CBCs is recommended for patients on antipsychotic treatment.1

CBC=complete blood count; PPI=proton pump inhibitor.

Drug interactions

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 in cariprazine1

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:
  • For 4.5 mg/day, the dosage should be reduced to 1.5 mg/day or 3 mg/day
  • For 1.5 mg/day, adjust regimen to every other day

Initiating VRAYLAR therapy while already on a strong CYP3A4 inhibitor

  • 1.5 mg of VRAYLAR on Day 1 and Day 3 with no dose on Day 2
  • From Day 4 onward, 1.5 mg/day of VRAYLAR then increase to a maximum dose of 3 mg/day

When the CYP3A4 inhibitor is withdrawn, VRAYLAR dosage may need to be increased

Clinical Impact
Intervention
CYP3A4 inducers
Not recommended
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 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.
SEE MORE +
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 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.