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Efficacy Data for REXULTI® (brexpiprazole) as Adjunctive Treatment for MDD

Explore the efficacy of REXULTI at 2 doses across 2 clinical studies

Efficacy Data for REXULTI® (brexpiprazole) as Adjunctive Treatment for MDD

Explore the efficacy of REXULTI at 2 doses across 2 clinical studies

Video: Clinical Data for REXULTI® (brexpiprazole)
as Adjunctive Treatment for Major Depressive Disorder (MDD)

Watch Dr. Jason Bermak review data from clinical trials.

Dr. Bermak is a paid consultant of Otsuka America Pharmaceutical, Inc. and Lundbeck.

Hello, I’m Doctor Jason Bermak.
Welcome to: “Efficacy Profile of REXULTI® (brexpiprazole) as Adjunctive Treatment for Major Depressive Disorder”

REXULTI is indicated for:

Use as an adjunctive therapy to antidepressants in adults with major depressive disorder, or MDD.

REXULTI has the following BOXED WARNINGS:

SUICIDAL THOUGHTS AND BEHAVIORS and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS.

Now, let’s review the efficacy profile of REXULTI as adjunctive therapy to antidepressants in adults with MDD as demonstrated by 2 pivotal trials evaluating safety and efficacy.

Let’s discuss how the efficacy and safety of REXULTI was assessed in patients with inadequate response to antidepressants.

For our purposes, the pivotal trials for REXULTI will be referred to as Studies 1 and 2.

Patients included in the study were adults meeting the DSM-IV-TR criteria for MDD. Patients with or without anxiety were permitted in the study.1

Patients had an inadequate response to 1 to 3 courses of antidepressant therapy at screening.1

Both Studies 1 and 2 were designed to confirm that the patients were having an inadequate response to their current treatment during an 8-week, single-blinded, prospective treatment phase.1,2

In the prospective phase, patients received either: escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, or venlafaxine XR, at the investigator’s discretion.

The antidepressants and their dose ranges are listed on the slide.1,2

In Study 1, patients who demonstrated a persistent inadequate response, as defined by pre-specified criteria, were randomized to REXULTI up to a target dose of 2 mg/day, plus the antidepressant, used in the prospective phase; or to placebo plus the antidepressant used in the prospective phase.1,3

In Study 2, patients were randomized in the same way to either REXULTI 1 mg/day or 3 mg/day plus antidepressant, or placebo plus antidepressant.2

The primary endpoint was change from baseline to Week 6 in MÅDRS total score.1,2

Shown here are pooled data on baseline patient demographics and clinical characteristics from Studies 1 and 2 gathered at the time of randomization after the prospective phase of antidepressant alone.

Age, BMI, and gender were balanced between the treatment arms.4

49.1% of patients receiving placebo plus antidepressant and 48.9% of patients receiving REXULTI plus antidepressant across all doses reported symptoms of anxiety at baseline.5

The MÅDRS total score at baseline was 26.9 for the placebo plus antidepressant group, and 26.8 for the REXULTI (all doses) plus antidepressant group.4

Here we see the results for the primary endpoint in Study 1—change from baseline to Week 6 in the MÅDRS total score.1,3

REXULTI 2 mg plus antidepressant demonstrated a statistically significant change in MÅDRS total score at week 6, compared with placebo plus antidepressant with a P value equal to 0.0002, which resulted in 62% greater reduction in MÅDRS total score in patients treated with REXULTI plus antidepressant, over placebo plus antidepressant.1

In Study 2, REXULTI 3 mg/day in combination with antidepressant was superior to placebo plus antidepressant in mean change in total MÅDRS scores. The 1 mg dose of REXULTI plus antidepressant was not considered statistically superior to placebo.2,3

Adverse reactions that occurred in 2% or more of patients receiving all doses of REXULTI plus antidepressant treatment—or ADT— from the two 6-week, placebo-controlled studies are shown.

The most common adverse reactions in the 2 MDD clinical trials were weight increase and akathisia.

Akathisia was reported by 9% of patients in the REXULTI plus ADT therapy groups, and 2% of the placebo plus ADT patients.

Weight increase was reported by 7% of patients treated with REXULTI plus ADT and 2% of patients in the placebo plus ADT group.

Now let’s take a closer look at the data concerning dose-related adverse reactions that occurred in 2% or more of patients treated with REXULTI plus ADT and the placebo plus ADT group.3

As you can see, for REXULTI, akathisia occurred in 4% of patients at the 1 mg dose, 7% at the target dose of 2 mg, and 14% at the maximum dose of 3 mg.3

Both akathisia and restlessness increased with increases in dose.3

Additional adverse events are also shown in the slide.7,8

INDICATION and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)

INDICATION

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants in adults with major depressive disorder

IMPORTANT SAFETY INFORMATION

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients.

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Contraindication: In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. For chronic treatment, use the lowest dose and shortest duration of REXULTI needed to produce a clinical response. If signs and symptoms of TD appear, drug discontinuation should be considered.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed in patients treated with REXULTI. Monitor weight at baseline and frequently thereafter.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking REXULTI. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping REXULTI if such urges develop.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in this class. 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 REXULTI 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. Generally, the risk is greatest during initial dose titration and when increasing the dose. Monitor in patients vulnerable to hypotension, and those with cardiovascular and cerebrovascular diseases.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: REXULTI may cause seizures and should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Body Temperature Dysregulation: Use REXULTI with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. including REXULTI, and should be used with caution in patients at risk for aspiration.

Potential for Cognitive and Motor Impairment: REXULTI has the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are reasonably certain REXULTI does not affect them adversely.

Concomitant Medication: Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.

Most commonly observed adverse reactions: In clinical trials, the most common adverse reactions were:

  • Major Depressive Disorder (MDD) (adjunctive treatment to antidepressant therapy; ≥5% incidence and at least twice the rate of placebo for REXULTI vs. placebo): akathisia and weight increase

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI during pregnancy have not been conducted. REXULTI should be used during pregnancy only if the benefit justifies the risk to the fetus.

Lactation: It is not known if REXULTI is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

References:

  • Thase ME, Youakim JM, Skuban A, et al. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015;76:1224-1231.
  • Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015;76:1232-1240.
  • REXULTI [prescribing information]. Tokyo, Japan: Otsuka Pharmaceutical Co, Ltd.
  • Thase ME, Zhang P, Skuban A, et al. Efficacy of adjunctive brexpiprazole in patients with major depressive disorder: a clinical overview. Curr Psychiatry Rev. 2016;12:291-301.
  • Data on file (REX-250).
  • Data on file (REX-249).
  • Data on File (REX-162).
  • Data on File (REX-024).

Dr. Jason Bermak, MD, PhD

Medical Director & Psychiatrist, SF-Care Inc.

Dr. Bermak is a paid
consultant of Otsuka
America Pharmaceutical,
Inc. and Lundbeck.

Superior reduction in MÅDRS total score

REXULTI—statistically superior reduction in mean MÅDRS total score vs placebo + ADT in one 6-week clinical trial at study endpoint1,2

*p<0.05, **p<0.01, ***p<0.001 vs placebo.

MÅDRS baseline (SD): placebo + ADT (n=178), 27.3 (5.6); REXULTI 2 mg/day + ADT (n=175), 26.9 (5.7).

Mean change from baseline (SE) at 6 weeks across 2 clinical trials1,2,4

  • 2-mg/day recommended dose: -5.2 (0.6) for placebo + ADT vs -8.4 (0.6) for REXULTI + ADTa
  • 3-mg/day maximum dose: -6.3 (0.5) for placebo + ADT vs -8.3 (0.5) for REXULTI + ADT
    • MÅDRS baseline (SD): placebo + ADT (n=203), 26.5 (5.2); REXULTI 3 mg/day + ADT (n=213), 26.5 (5.3)
    • -2.0 difference in mean reduction vs placebo at 6 weeks (95% CI: -3.4, -0.5) p=0.0079

ADT: antidepressant therapy; MÅDRS: Montgomery-Åsberg Depression Rating Scale; SD: standard deviation; SE: standard error.

aDosage statistically significantly superior to placebo.

The efficacy and safety of REXULTI was also studied in patients randomized to receive 1 mg/day in Study 2 (n=211). Results for the REXULTI 1 mg + ADT group for the primary efficacy parameter were not statistically significant when compared with placebo + ADT p=0.0737. At the end of Week 6, all patients had the option to enter an open-label, flexible-dose 52-week study (N=2084).1,2,4,5

Contraindication:

In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

 


Two Phase 3 clinical trials for adult MDD patients with inadequate response

  • Studies included 3 phases: a screening phase to determine prior inadequate response to 1-3 ADTs; an 8-week single-blind prospective phase with a choice of 6 ADTs* + placebo; and a 6-week double-blind randomization phase with brexpiprazole at 2 or 3 mg/day + ADT compared to placebo + ADT in those meeting criteria for inadequate response 1,4
  • Entry into randomization phase with brexpiprazole treatment + ADT was based on specific criteria to determine consistent inadequate response throughout the 8-week prospective phase 1,4†
  • Primary endpoint was the change in MÅDRS total score at the end of the 6-week randomization phase in patients receiving brexpiprazole + ADT compared to placebo + ADT 1,4

*SSRIs that were included in these studies: Escitalopram; Sertraline; Paroxetine CR; Fluoxetine. SNRIs that were included in these studies: Duloxetine DR; Venlafaxine XR.

Persistent inadequate response criteria (prospective phase) included: <50% reduction in HAM-D17 Total Score and ≥14 HAM-D17 score at Week 8; <50% reduction in MÅDRS Total Score and Clinical Global Impression-Improvement Score of ≥3 at each scheduled visit.1,4

Patients with persistent inadequate response to 8 weeks of ADT entered the randomized double-blind treatment phase.

ADT: antidepressant therapy; HAM-D17: 17-item Hamilton Depression Rating Scale.


View safety profile

Examine the safety profile for REXULTI.

Get dosing information

Learn about once-daily treatment with a target dose of 2 mg.2

INDICATIONS and IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)

INDICATIONS

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants in adults with major depressive disorder
  • Treatment of schizophrenia in adults

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients.

Contraindication: In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. For chronic treatment, use the lowest dose and shortest duration of REXULTI needed to produce a clinical response. If signs and symptoms of TD appear, drug discontinuation should be considered.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed in patients treated with REXULTI. Monitor weight at baseline and frequently thereafter.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking REXULTI. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping REXULTI if such urges develop.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in this class. 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 REXULTI 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. Generally, the risk is greatest during initial dose titration and when increasing the dose. Monitor in patients vulnerable to hypotension, and those with cardiovascular and cerebrovascular diseases.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: REXULTI may cause seizures and should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Body Temperature Dysregulation: Use REXULTI with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. including REXULTI, and should be used with caution in patients at risk for aspiration.

Potential for Cognitive and Motor Impairment: REXULTI has the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are reasonably certain REXULTI does not affect them adversely.

Concomitant Medication: Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.

Most commonly observed adverse reactions: In clinical trials, the most common adverse reactions were:

  • Major Depressive Disorder (MDD) (adjunctive treatment to antidepressant therapy; ≥5% incidence and at least twice the rate of placebo for REXULTI vs. placebo): akathisia and weight increase
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): weight increased

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI during pregnancy have not been conducted. REXULTI should be used during pregnancy only if the benefit justifies the risk to the fetus.

Lactation: It is not known if REXULTI is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

References:

  • Thase ME, Youakim JM, Skuban A, et al. Efficacy and safety of adjunctive 2 mg brexpiprazole in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015;76(9):1224-1231.
  • Rexulti [prescribing information]. Tokyo, Japan: Otsuka Pharmaceutical Co., Ltd.
  • Data on file (REX-014).
  • Thase ME, Youakim JM, Skuban A, et al. Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study. J Clin Psychiatry. 2015;76(9):1232-1240.
  • Nelson JC, Skuban A, Hobart M, Zhang P, Weiss C, Weiller E. The metabolic tolerability profile of adjunct brexpiprazole (OPC-34712) in major depressive disorder. Poster presented at: American Society of Clinical Psychopharmacology Annual Meeting; June 22-25, 2015; Miami, FL.
IMPORTANT SAFETY INFORMATION and INDICATIONS for REXULTI® (brexpiprazole)
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IMPORTANT SAFETY INFORMATION

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increase the risk of suicidal thoughts and behaviors in patients aged 24 years and younger. Monitor for clinical worsening and emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients.

Contraindication: In patients with known hypersensitivity reaction to brexpiprazole or any of its components. Reactions have included: rash, facial swelling, urticaria and anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: In clinical trials, elderly patients with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability. Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of REXULTI, intensive symptomatic treatment, and monitoring.

Tardive Dyskinesia (TD): Risk of TD, and the potential to become irreversible, are believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after a relatively brief treatment period, even at low doses, or after discontinuation of treatment. For chronic treatment, use the lowest dose and shortest duration of REXULTI needed to produce a clinical response. If signs and symptoms of TD appear, drug discontinuation should be considered.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment.
  • Dyslipidemia: Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment.
  • Weight Gain: Weight gain has been observed in patients treated with REXULTI. Monitor weight at baseline and frequently thereafter.

Pathological Gambling and Other Compulsive Behaviors: Intense urges, particularly for gambling, and the inability to control these urges have been reported while taking REXULTI. Other compulsive urges have been reported less frequently. Prescribers should ask patients or their caregivers about the development of new or intense compulsive urges. Consider dose reduction or stopping REXULTI if such urges develop.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia and neutropenia have been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in this class. 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 REXULTI 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. Generally, the risk is greatest during initial dose titration and when increasing the dose. Monitor in patients vulnerable to hypotension, and those with cardiovascular and cerebrovascular diseases.

Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls causing fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: REXULTI may cause seizures and should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Body Temperature Dysregulation: Use REXULTI with caution in patients who may experience conditions that increase body temperature (e.g., strenuous exercise, extreme heat, dehydration, or concomitant use with anticholinergics).

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotics. including REXULTI, and should be used with caution in patients at risk for aspiration.

Potential for Cognitive and Motor Impairment: REXULTI has the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are reasonably certain REXULTI does not affect them adversely.

Concomitant Medication: Dosage adjustments are recommended in patients who are known cytochrome P450 (CYP) 2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers.

Most commonly observed adverse reactions: In clinical trials, the most common adverse reactions were:

  • Major Depressive Disorder (MDD) (adjunctive treatment to antidepressant therapy; ≥5% incidence and at least twice the rate of placebo for REXULTI vs. placebo): akathisia and weight increase
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): weight increased

Dystonia: Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy: Adequate and well-controlled studies to assess the risks of REXULTI during pregnancy have not been conducted. REXULTI should be used during pregnancy only if the benefit justifies the risk to the fetus.

Lactation: It is not known if REXULTI is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

INDICATIONS

REXULTI is indicated for:

  • Use as an adjunctive therapy to antidepressants in adults with major depressive disorder
  • Treatment of schizophrenia in adults

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.