The following information comes from DailyMed, an FDA label information provider.
The following serious adverse reactions of Rexulti (brexpiprazole) are discussed in greater detail in other sections:
- MDD: Weight increased and akathisia (â¥5% and at least twice the rate for placebo)
- Schizophrenia: Weight increased (â¥4% and at least twice the rate for placebo)
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.
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.
Safety and effectiveness of REXULTI have not been established in pediatric patients.
Adverse Reactions
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Increased Mortality in Elderly Patients with Dementia-Related Psychosis
- Suicidal Thoughts and Behaviors in Adolescents and Young Adults
- Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis
- Neuroleptic Malignant Syndrome (NMS)
- Tardive Dyskinesia
- Metabolic Changes
- Pathological Gambling and Other Compulsive Behaviors
- Leukopenia, Neutropenia, and Agranulocytosis
- Orthostatic Hypotension and Syncope
- Falls
- Seizures
- Body Temperature Dysregulation
- Dysphagia
- Potential for Cognitive and Motor Impairment
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Major Depressive Disorder
The safety of REXULTI was evaluated in 1054 patients (18 to 65 years of age) diagnosed with MDD who participated in two 6-week placebo-controlled, fixed-dose clinical trials in patients with major depressive disorder in which REXULTI was administered at doses of 1 mg to 3 mg daily as adjunctive treatment to continued antidepressant therapy; patients in the placebo group continued to receive antidepressant therapy.
Adverse Reactions Reported As Reasons for Discontinuation of Treatment
A total of 3% (17/643) of REXULTI-treated patients and 1% (3/411) of placebo-treated patients discontinued due to adverse reactions.
Common Adverse Reactions
Adverse reactions associated with the adjunctive use of REXULTI (incidence of 2% or greater and adjunctive REXULTI incidence greater than adjunctive placebo) that occurred during acute therapy (up to 6-weeks in patients with MDD) are shown in Table 8.
| Placebo (N=411) | REXULTI | ||||
|---|---|---|---|---|---|
| 1 mg/day (N=226) | 2 mg/day (N=188) | 3 mg/day (N=229) | All REXULTI (N=643) | ||
| Gastrointestinal Disorders | |||||
| Constipation | 1% | 3% | 2% | 1% | 2% |
| General Disorders and Administration Site Conditions | |||||
| Fatigue | 2% | 3% | 2% | 5% | 3% |
| Infections and Infestations | |||||
| Nasopharyngitis | 2% | 7% | 1% | 3% | 4% |
| Investigations | |||||
| Weight Increased | 2% | 7% | 8% | 6% | 7% |
| Blood Cortisol Decreased | 1% | 4% | 0% | 3% | 2% |
| Metabolism and Nutrition | |||||
| Increased Appetite | 2% | 3% | 3% | 2% | 3% |
| Nervous System Disorders | |||||
| Akathisia | 2% | 4% | 7% | 14% | 9% |
| Headache | 6% | 9% | 4% | 6% | 7% |
| Somnolence | 0.5% | 4% | 4% | 6% | 5% |
| Tremor | 2% | 4% | 2% | 5% | 4% |
| Dizziness | 1% | 1% | 5% | 2% | 3% |
| Psychiatric Disorders | |||||
| Anxiety | 1% | 2% | 4% | 4% | 3% |
| Restlessness | 0% | 2% | 3% | 4% | 3% |
| *Adverse reactions that occurred in â¥2% of REXULTI-treated patients and greater incidence than in placebo-treated patients |
Dose-Related Adverse Reactions in the MDD Trials
In Studies 1 and 2, among the adverse reactions that occurred at â¥2% incidence in the patients treated with REXULTI + ADT, the incidences of akathisia and restlessness increased with increases in dose.
Schizophrenia
The safety of REXULTI was evaluated in 852 patients (18 to 65 years of age) diagnosed with schizophrenia who participated in two 6-week placebo-controlled, fixed-dose clinical trials in which REXULTI was administered at daily doses of 1 mg, 2 mg, and 4 mg.
Common Adverse Reactions
Adverse reactions associated with REXULTI (incidence of 2% or greater and REXULTI incidence greater than placebo) during short-term (up to 6 weeks) trials in patients with schizophrenia are shown in Table 9.
| Placebo (N=368) | REXULTI | ||||
|---|---|---|---|---|---|
| 1 mg/day (N=120) | 2 mg/day (N=368) | 4 mg/day (N=364) | ALL REXULTI (N=852) | ||
| Gastrointestinal Disorders | |||||
| Dyspepsia | 2% | 6% | 2% | 3% | 3% |
| Diarrhea | 2% | 1% | 3% | 3% | 3% |
| Investigations | |||||
| Weight Increased | 2% | 3% | 4% | 4% | 4% |
| Blood Creatine Phosphokinase Increased | 1% | 4% | 2% | 2% | 2% |
| Nervous System Disorders | |||||
| Akathisia | 5% | 4% | 5% | 7% | 6% |
| Tremor | 1% | 2% | 2% | 3% | 3% |
| Sedation | 1% | 2% | 2% | 3% | 2% |
| *Adverse reactions that occurred in â¥2% of REXULTI-treated patients and greater incidence than in placebo-treated patients |
Extrapyramidal Symptoms
Major Depressive Disorder
The incidence of reported extrapyramidal symptoms (EPS)-related adverse reactions, excluding akathisia, was 6% for REXULTI + ADT-treated patients versus 3% for placebo + ADT-treated patients. The incidence of akathisia events for REXULTI + ADT-treated patients was 9% versus 2% for placebo + ADT-treated patients.
In the 6-week placebo-controlled MDD studies, data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Score (AIMS) for dyskinesia. The mean change from baseline at last visit for REXULTI + ADT-treated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in REXULTI + ADT-treated patients versus placebo + ADT-treated patients for the BARS (4% versus 0.6%) and the SAS (4% versus 3%).
Schizophrenia
The incidence of reported EPS-related adverse reactions, excluding akathisia, was 5% for REXULTI-treated patients versus 4% for placebo-treated patients. The incidence of akathisia events for REXULTI-treated patients was 6% versus 5% for placebo-treated patients.
In the 6-week placebo-controlled, fixed-dose schizophrenia studies, data was objectively collected on the Simpson-Angus Rating Scale (SAS) for EPS, the Barnes Akathisia Rating Scale (BARS) for akathisia and the Abnormal Involuntary Movement Scale (AIMS) for dyskinesia. The mean change from baseline at last visit for REXULTI-treated patients for the SAS, BARS and AIMS was comparable to placebo-treated patients. The percentage of patients who shifted from normal to abnormal was greater in REXULTI-treated patients versus placebo for the BARS (2% versus 1%) and the SAS (7% versus 5%).
Dystonia
Symptoms of dystonia may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first-generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.
Other Adverse Reactions Observed during the Premarketing Evaluation of REXULTI
Other adverse reactions (â¥1% frequency and greater than placebo) within the short-term, placebo-controlled trials in patients with MDD and schizophrenia are shown below. The following listing does not include adverse reactions: 1) already listed in previous tables or elsewhere in the labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have clinically significant implications, or 5) which occurred at a rate equal to or less than placebo.
Eye Disorders: Vision Blurred
Gastrointestinal Disorders: Nausea, Dry Mouth, Salivary Hypersecretion, Abdominal Pain, Flatulence
Infections and Infestations: Urinary Tract Infection
Investigations: Blood Prolactin Increased
Musculoskeletal and Connective Tissue Disorders: Myalgia
Psychiatric Disorders: Abnormal Dreams, Insomnia
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis
Postmarketing Experience
The following adverse reaction has been identified during post-approval use of REXULTI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Nervous System disorders: Neuroleptic Malignant Syndrome
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