INDICATIONREXULTI® (brexpiprazole) is indicated for: • Treatment of schizophrenia in adults

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSISElderly 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.

Please see IMPORTANT SAFETY INFORMATION on pages 5 and 6.

Consider Tom:AGE: 36BMI: 31OCCUPATION: Currently unemployed• On an atypical antipsychotic initiated

at last hospitalization• Unresolved symptoms: hallucinations,

paranoid delusions, social withdrawal, and agitation

• Caregiver expresses interest in changing oral atypical antipsychotic

Atypical antipsychotic drugs have been associated with metabolic changes including: hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain.

Are your patients with schizophrenia still struggling with unresolved symptoms?

Model portrayal.© 2020 Otsuka America Pharmaceutical, Inc. All rights reserved.

March 2020 11US20EBP0020

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NSS

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-20.0

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ap<0.0001 vs placebo.3Adapted with permission.

Placebo (n=358)

REXULTI 4 mg/day (n=359)

-20

-16

-12

-8

-4

0

0 1 2 3 4 5 6Week

20-point reduction

from baseline

(7 more than placebo)3,a

20-point reduction

from baseline

(7 more than placebo)3,a

REXULTI® (brexpiprazole) 4 mg reduced PANSS total score by 20 points from baseline across 2 trialsREXULTI pivotal trial design1,2

Two 6-week, randomized, placebo-controlled, fixed-dose pivotal trials conducted in patients who met DSM-IV-TR criteria for SZ and would benefit from hospitalization or continued hospitalization for an acute exacerbation of symptoms1,2

Treatment initiated at 1 mg/day on Days 1-4, titrated to 2 mg/day on Days 5-7, then maintained or increased to 4 mg/day on Day 8, depending on treatment arm

Primary endpoint was change in total PANSS score from baseline to Week 6

Study 3 and Study 4: REXULTI 4 mg/day—reduction in PANSS total score vs placebo in pooled data at 6 weeks3

DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision); LS, least squares; PANSS, Positive and Negative Syndrome Scale; SZ, schizophrenia.

Please see IMPORTANT SAFETY INFORMATION on pages 5 and 6.

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

2

Reduction of PANSS total score from baseline in two pivotal trials at 6 weeksIn Study 3, at the 2-mg dose and the 4-mg dose, respectively, the reduction from baseline was -8.7 (95% CI: -13.1, -4.4), p<0.0001, and 7.6 (95% CI: -12.0, -3.1), p=0.0006.1 In Study 4, at the 1-mg dose, the 2-mg dose, and the 4-mg dose, respectively, the reduction from baseline was -3.4 (95% CI: -8.1, 1.3), p=0.1588, -3.1 (95% CI: -7.2, 1.1), p=0.1448, and -6.5 (95% CI: -10.6, -2.4), p=0.0022.2

CI, confidence interval.

Placebo (n=368)REXULTI (all doses) (n=852)

Akathisia5%

Weight increase4%

2%

Diarrhea3%

2%

3%

2%Dyspepsia

Tremor3%6%

1%

Blood creatinephosphokinase increase

2%

1%

Sedation2%

1%

Most common adverse reaction occurring in ≥4% of patients and at least twice the rate of placebo was weight increase

Demonstrated safety profile across 2 pivotal trials

Study 3 and Study 4: REXULTI® (brexpiprazole)—adverse reactions that occurred in ≥2% of patients and greater incidence vs placebo from two 6-week pivotal trials

Important Warning and Precaution for Cerebrovascular Adverse Events, Including StrokeIn 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.

In both trials, akathisia occurred most often during the first 3 weeks of treatment, and no incidences resulted in treatment discontinuation1,2

The safety population included patients receiving 1 mg/day

3 Please see IMPORTANT SAFETY INFORMATION on pages 5 and 6.

91hours

4

/day

Pills actual size.

Days 1-4 Days 5-7 Days 8+

4

21 2 TO

Starting dose

Target dose

Clear titration schedule and once-daily dosing

REXULTI® (brexpiprazole)—recommended target dose: 2 mg/day to 4 mg/day

The recommended starting dose is 1 mg/day on Days 1-4. Titrate to 2 mg/day on Days 5-7, then maintain or increase to 4 mg/day on Day 8 based on clinical response and tolerability. Periodically reassess to determine continued need and appropriate dose.

4-hour peak plasma concentration (after administration)

Half-life

Pills not actual size.

Once-daily dosing

No food requirements

Dose adjustments for REXULTI• Dose adjustments may be needed in patients with hepatic or renal impairment • Administer half the dose when given with strong CYP2D6 or strong CYP3A4 inhibitors, or in patients who are known

CYP2D6 poor metabolizers • Administer a quarter of the dose with the concurrent use of both strong/moderate CYP2D6 inhibitors and strong/

moderate CYP3A4 inhibitors. Likewise, administer a quarter of the dose in patients who are known CYP2D6 poor metabolizers taking strong/moderate CYP3A4 inhibitors

• Double the dose over 1 to 2 weeks when administering with strong CYP3A4 inducers

Please see IMPORTANT SAFETY INFORMATION on pages 5 and 6. 4

IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole)WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSISElderly 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 including REXULTI. 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.

5 (continued)Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNING.

References: 1. Correll CU, Skuban A, Ouyang J, et al. Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2015;172(9):870-880. 2. Kane JM, Skuban A, Ouyang J, et al. A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res. 2015;164(1-3):127-135. 3. Correll CU, Skuban A, Hobart M, et al. Efficacy of brexpiprazole in patients with acute schizophrenia: review of three randomized, double-blind, placebo-controlled studies. Schizophr Res. 2016;174(1-3):82-92.

© 2020 Otsuka America Pharmaceutical, Inc. All rights reserved. March 2020 11US20EBP00206

IMPORTANT SAFETY INFORMATION for REXULTI® (brexpiprazole) (continued)

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:

• 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).