Welcome to the latest edition of our Guidelines+ Monographs Series. In this installment, we will delve into the medication brexpiprazole, marketed under the brand name Rexulti by Otsuka America Pharmaceutical, Inc and Lundbeck LLC. Rexulti, an atypical antipsychotic, received initial approval in 2015. It is indicated for use as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) in adults, as well as for the treatment of schizophrenia in adults and pediatric patients aged 13 years and older. Additionally, Rexulti is utilized for the treatment of agitation associated with dementia due to Alzheimer’s disease.
In the following sections, we will provide a comprehensive overview of brexpiprazole and analyze its positioning across various guidelines for its approved indications.
Note* – This Guidelines+ Monographs for brexpiprazole (Rexulti) is current as of September 2024. Consult our clinical guidelines library and/or or medication information lookup tool to ensure you are always accessing the most current information.
Medication Overview:
- Brand name: Rexulti
- Generic name: brexpiprazole
- Manufacturer(s): Otsuka America Pharmaceutical, Inc and Lundbeck LLC
- Initial FDA Approval: July 2015
- Available Dosages: Tablets: .25 mg, .5 mg, 1 mg, 2 mg, 3 mg, and 4 mg
Indications and FDA Approval Details
| Indicated Condition | Indicated For | Age | Date Approved |
|---|---|---|---|
Major Depressive Disorder (MDD) | Use as an adjunctive therapy to antidepressants for the treatment of (MDD) in adults | Adult | July 2015 |
Schizophrenia | Treatment | Adult | Sept 2016 |
| Schizophrenia | Treatment | Pediatric 13 – 17 years old | Jan 2022 |
Agitation associated with dementia due to Alzheimer’s disease | Treatment of agitation associated with dementia due to Alzheimer’s disease | Adult | May 2023 |
Dosage Forms and Strengths
| Dosage Form | Strength |
|---|---|
| Oral Tablet | .25 mg |
| Oral Tablet | .5 mg |
| Oral Tablet | 1 mg |
| Oral Tablet | 2 mg |
| Oral Tablet | 3 mg |
| Oral Tablet | 4 mg |
Dosage and Administration
| Indication | Starting Dosage | Recommended Target Dosage | Maximum Dosage |
|---|---|---|---|
| MDD Adults | 0.5 mg/day or 1 mg/day | 2 mg/day | 3 mg/day |
| Schizophrenia Adults | 1 mg/day | 2 to 4 mg/day | 4 mg/day |
| Schizophrenia Pediatric | 0.5 mg/day | 2 to 4 mg/day | 4 mg/day |
| Agitation associated with dementia due to Alzheimer’s disease | 0.5 mg/day | 2 mg/day | 3 mg/day |
Boxed Warning
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS
See full prescribing information for complete boxed warning.
- 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.
- Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Safety and effectiveness of REXULTI have not been established in pediatric patients with MDD.
Warnings and Precautions
- Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack).
- Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
- Tardive Dyskinesia: Discontinue if clinically appropriate.
- Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain.
- Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation.
- Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing REXULTI if a clinically significant decline in WBC occurs in absence of other causative factors.
- Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
- Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
- Potential for Cognitive and Motor Impairment: Use caution when operating machinery.
Adverse Reactions
Most common adverse reactions in adults were:
- MDD: Weight increased, somnolence, and akathisia (≥5% and at least twice the rate for placebo)
- Schizophrenia: Weight increased (≥4% and at least twice the rate for placebo)
- Agitation associated with dementia due to Alzheimer’s disease: Nasopharyngitis, dizziness (≥4% and at least twice the rate for placebo
Now that we’ve covered the basic monograph information for dupilumab, let’s take a closer look at how Rexulti is currently recommended in various clinical practice guidelines. We will categorize the list based on the indication, and then provide a general summary table at the end.
Specific Inclusions of Atypical Antipsychotics (Including brexpiprazole) in Clinical Guidelines
- Management of Major Depressive Disorder (MDD)
- Authoring Societies: Veteran Health Administration/Department of Defense (VA/DoD)
- Publication: April 25, 2022
- In cases where patients have shown only partial or no response to initial pharmacotherapy monotherapy, augmentation with a Second-Generation Antipsychotic (SGA) may be considered. Three atypical antipsychotics have been approved by the FDA for Major Depressive Disorder (MDD) as adjunctive treatment/augmentation: aripiprazole, brexpiprazole, and quetiapine-XR.
- Treatment of Patients With Schizophrenia
- Authoring Society: American Psychiatric Association (APA)
- Publication: August 31, 2020
- Pharmacotherapy: APA recommends that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects.
- Management of First-Episode Psychosis and Schizophrenia
- Authoring Society: VA/DoD
- Publication: May 11, 2023
- We recommend the use of an antipsychotic medication other than clozapine for the treatment of an acute episode in individuals with schizophrenia or first-episode psychosis who have previously responded to antipsychotic medications. The choice of antipsychotic medication should be based on an individualized evaluation that considers patient characteristics and side effect profiles of the different antipsychotic medications.
- We recommend the use of an antipsychotic medication for the maintenance treatment of schizophrenia to prevent relapse and hospitalization in individuals with schizophrenia who have responded to treatment. Choice of antipsychotic medication should be based on an individualized evaluation that considers patient-specific characteristics and side effect profiles of the different antipsychotic medications
This concludes our Guidelines+ Monographs for brexpiprazole (Rexulti). This list is current as of September 2024 and may be updated over time as new indications are approved and/or new guidelines published or updated. Sign up for alerts and stay informed on the latest published guidelines and articles.
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