REXULTI® (brexpiprazole) + antidepressants:
safety profile in adult patients with MDD

Adverse reactions that occurred in 2% of patients and with greater incidence than placebo from two 6-week pivotal trials across all doses

Rates for ADTa + REXULTI (all doses; n=643) vs ADTa + placebo (n=411)

  • Akathisia 9% vs 2%
  • Headache 7% vs 6%
  • Weight increase 7% vs 2%
  • Somnolence 5% vs 0.5%
  • Nasopharyngitis 4% vs 2%
  • Tremor 4% vs 2%
  • Fatigue 3% vs 2%
  • Increased appetite 3% vs 2%
  • Anxiety 3% vs 1%
  • Dizziness 3% vs 1%
  • Restlessness 3% vs 0%
  • Blood cortisol decrease 2% vs 1%
  • Constipation 2% vs 1%
  • Increased appetite 3% vs 2%
  • Anxiety 3% vs 1%
  • Dizziness 3% vs 1%
  • Restlessness 3% vs 0%
  • Blood cortisol decrease 2% vs 1%
  • Constipation 2% vs 1%
  • The most common adverse reactions (≥5%) and at least twice the rate of placebo for ADT +
    REXULTI vs ADT + placebo were weight increased (7% vs 2%), somnolence (5% vs 0.5%), and
    akathisia (9% vs 2%).
  • In patients taking ADT + REXULTI (n=643, all doses) vs ADT + placebo (n=411), the incidence of
    decreased libido was 0.6% vs 0.2%, respectively1

Two adverse reactions were dose-dependent

Dose Dependent Incidence Chart

Two adverse reactions were dose-dependent

Dose Dependent Incidence Chart

aThe antidepressants studied included SSRIs and SNRIs.
The safety population included patients randomized between 1 mg/day and 3 mg/day of ADT + REXULTI.

ADT, antidepressant treatment; MDD, major depressive disorder; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

 

REXULTI + antidepressants: few discontinuations due to adverse reactions over 6 weeks across all doses

Discontinuation rates for antidepressant
treatment + REXULTI vs antidepressant treatment + placebo

discontinuation rates REXULTI vs placebo diagram Discontinuation Rates diagram ADT + REXULTI (n=643) 3 % ADT + Placebo (n=411) 1 %

Discontinuation rates for antidepressant treatment + REXULTI vs antidepressant treatment + placebo

discontinuation rates REXULTI vs placebo diagram Discontinuation Rates diagram ADT + Placebo (n=411) 1 % ADT + REXULTI (n=643) 3 %

Discontinuations due to most common adverse events

discontinuation rates REXULTI vs placebo chart Discontinuation Rates chart 0 % 0 % 0 . 9 % 0 % Due t o a k athisia 3 Due t o w eight inc r eased 4 A D T + RE X U L TI (all dose s ) (n= 6 43) A D T + Pla c ebo (n= 4 11)

Discontinuations due to most common adverse events

discontinuation rates REXULTI vs placebo chart Discontinuation Rates chart Due to akathisia 3 Due to weight increased 4 ADT + REXULTI (all doses) 0.9 (n=643) ADT + REXULTI (all doses) (n=643) ADT + Placebo (n=411) ADT + Placebo (n=411) % 0 % 0 % 0 %
 

REXULTI + antidepressants: metabolic profile in short and long-term trials

METABOLIC CHANGE

Percentage of patients whose values shifted from baseline to post-baseline5,6

Percentage of patients whose values shifted from baseline to post-baseline5,6

Triglycerides table

Discontinuation due to weight increase across all doses

Discontinuation due to weight increase across all doses

bThe REXULTI open-label MDD trials5:

  • After the conclusion of the 6-week trials, patients who elected to remain in a trial, patients from Phase 2 trials, and de novo patients were treated with flexible doses of antidepressants + REXULTI in a 52-week, open-label trial, where no placebo control was included
  • Safety data were collected at regular intervals throughout the 52-week, open-label trial

HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Weight change results across all doses7-10

Weight change results across all doses7-10

weight change results across all doses Weight Change chart A DT + Placebo A DT + REXULTI 2 % of patients 4 % 8 of patients 30 % of patients 0 % 9 of patients 0 . 2 % 9 of patients 4 % of patients A DT + REXULTI W eight chan g e 7% inc r ease in body w eight 7% dec r ease in body w eight Mean w eight inc r ease c 0 . 3 k g 1.5 k g 7 6 - w eek, fi x ed-dose pi v otal trials 5 2 - w eek, open-label, fl e xible-dose trials b 10
weight change results across all doses Weight Change chart ADT + Placebo ADT + REXULTI 2 % of patients 4 % 8 of patients 0 % 9 of patients 0 . 2 % 9 of patients W eight chan g e 7% inc r ease in body w eight 7% dec r ease in body w eight Mean w eight inc r ease c 0 . 3 k g 1.5 k g 7 6 - w eek, fixed-dose pivotal trials 30 % of patients 4 % of patients ADT + REXULTI W eight chan g e 7% inc r ease in body w eight 7% dec r ease in body w eight Mean w eight inc r ease c 5 2 - w eek, open-label, flexible-dose trials b 10

bThe REXULTI open-label MDD trials5:

  • After the conclusion of the 6-week trials, patients who elected to remain in a trial, patients from Phase 2 trials, and de novo patients were treated with flexible doses of antidepressants + REXULTI in a 52-week, open-label trial, where no placebo control was included
  • Safety data were collected at regular intervals throughout the 52-week, open-label trial

cStandard deviation for mean weight increase at 6 weeks was 2.2 kg for REXULTI and 1.7 kg for placebo, at 26 weeks was 4.7 kg for REXULTI, and at 52 weeks was 6.1 kg for REXULTI.9

The standard conversion for kilograms (kg) to pounds (lb) is 1 kg for 2.20462 lb.

Important Warning and Precaution for Metabolic Changes

Atypical antipsychotic agents have been associated with metabolic changes that include Hyperglycemia/Diabetes Mellitus, Dyslipidemia, and Weight Gain. Clinical monitoring is recommended.

Continue exploring REXULTI

Review results from pivotal clinical trials for REXULTI.

Review results from pivotal
clinical trials for REXULTI.

Pharmacodynamic ICN

Learn about binding affinities across
neurotransmitter systems.

IMPORTANT SAFETY INFORMATION
and INDICATIONS

 
  • Use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults
  • Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
  • Treatment of agitation associated with Alzheimer’s dementia (AAD)
ISI Block Title

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 without agitation associated with dementia due to Alzheimer’s disease.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased 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 with MDD.

Contraindication: In patients with known hypersensitivity 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 without agitation associated with dementia due to Alzheimer’s disease.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported in association with administration of antipsychotic drugs, including REXULTI. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). 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, appear to increase with duration of treatment and total cumulative dose of antipsychotic drugs. TD can develop after relatively brief treatment periods, 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, including REXULTI, have caused metabolic changes including:

  • Hyperglycemia/Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with diabetic ketoacidosis, hyperosmolar coma or death, have 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 patients with severe neutropenia.

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 be cautioned about operating hazardous machinery, including operating motor vehicles, 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 of adults, 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): weight increased, somnolence, and akathisia.
  • Schizophrenia (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): weight increased. Adverse reactions in patients 13 to 17 years of age were generally similar to those observed in adult patients.
  • Agitation associated with dementia due to Alzheimer’s disease (≥4% incidence and at least twice the rate of placebo for REXULTI vs. placebo): nasopharyngitis and dizziness.

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 for the treatment of major depressive disorder (MDD) in adults
  • Treatment of schizophrenia in adults and pediatric patients ages 13 years and older
  • Treatment of agitation associated with dementia due to Alzheimer’s disease

Limitations of Use: REXULTI is not indicated as an as needed (“prn”) treatment for agitation associated with dementia due to Alzheimer’s disease

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.