Rexulti Adverse Reactions

The following adverse reactions are discussed in more detail in other sections of the monograph: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions].
Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions].
Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis [see Precautions].
Neuroleptic Malignant Syndrome (NMS) [see Precautions].
Tardive Dyskinesia [see Precautions].
Metabolic Changes [see Precautions].
Pathological Gambling and Other Compulsive Behaviors [see Precautions].
Leukopenia, Neutropenia, and Agranulocytosis [see Precautions].
Orthostatic Hypotension and Syncope [see Precautions].
Falls [see Precautions].
Seizures [see Precautions].
Body Temperature Dysregulation [see Precautions].
Dysphagia [see Precautions].
Potential for Cognitive and Motor Impairment [see Precautions].
Prolactin [see Precautions].
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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.
Adjunctive Treatment in Major Depressive Disorder (MDD): The safety of Brexpiprazole (Rexulti) was evaluated 1,054 patients (18 to 65 years of age) diagnosed with MDD who participated in two 6-week, placebo-controlled, fixed-dose clinical studies in patients with major depressive disorder in which Brexpiprazole (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 [see Pharmacology: Pharmacodynamics: Clinical Studies: Adjunctive Treatment of Major Depressive Disorder under Actions].
Adverse Reactions Reported as Reasons for Discontinuation of Treatment: A total of 3% (17/643) of Brexpiprazole (Rexulti)-treated patients and 1% (3/411) of placebo-treated patients discontinued due to adverse reactions.
Adverse Reactions in Brexpiprazole (Rexulti) Studies for Adjunctive MDD in Adults: Adverse reactions associated with the adjunctive use of Brexpiprazole (Rexulti) (incidence of 2% or greater and adjunctive Brexpiprazole (Rexulti) incidence greater than adjunctive placebo) that occurred during acute therapy (up to 6-weeks in patients with MDD) are shown in Table 12. (See Table 12.)

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Dose-Related Adverse Reactions in the MDD trials: In Studies 1 and 2, among the adverse reactions that occurred at ≥2% incidence in the patients treated with Brexpiprazole (Rexulti)+ADT, the incidences of akathisia and restlessness increased with increases in dose.
Schizophrenia: The safety of Brexpiprazole (Rexulti) was evaluated 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 Brexpiprazole (Rexulti) was administered at daily doses of 1 mg, 2 mg and 4 mg [see Pharmacology: Pharmacodynamics: Clinical Studies: Schizophrenia under Actions].
Adverse Reactions Occurring at an Incidence of 2% or More in Patients Treated with Brexpiprazole (Rexulti) for Schizophrenia: Adverse reactions associated with Brexpiprazole (Rexulti) (incidence of 2% or greater and Brexpiprazole (Rexulti) incidence greater than placebo) during short-term (up to 6 weeks) trials in patients with schizophrenia are shown in Table 13. (See Table 13.)

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Agitation Associated with Dementia Due to Alzheimer's Disease: The safety of Brexpiprazole (Rexulti) was evaluated in 503 patients (51 to 90 years of age), with a probable diagnosis of agitation associated with dementia due to Alzheimer's disease, who participated in two 12-week placebo-controlled, fixed-dose clinical studies in which Brexpiprazole (Rexulti) was administered at daily doses of 2 mg to 3 mg [see Pharmacology: Pharmacodynamics: Clinical Studies: Agitation Associated with Dementia Due to Alzheimer's Disease under Actions].
Discontinuation of Treatment Due to Adverse Reactions: In two 12-week placebo-controlled, fixed-dose, clinical studies, a total of 5.6% (28/503) of patients treated with Brexpiprazole (Rexulti) and 4.8% (12/251) of patients treated with placebo discontinued due to adverse reactions.
Adverse Reactions Occurring at an Incidence of 2% or More in Patients Treated with Brexpiprazole (Rexulti) for Agitation Associated with Dementia Due to Alzheimer's Disease: Adverse reactions associated with Brexpiprazole (Rexulti) (incidence ≥2% and greater than placebo) during the 12-week fixed-dose clinical studies in geriatric patients for treatment of agitation associated with dementia due to Alzheimer's disease are shown in Table 14. (See Table 14.)

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Extrapyramidal Symptoms: Adjunctive Treatment of Major Depressive Disorder: The incidence of reported EPS-related adverse reactions, excluding akathisia, was 6% for Brexpiprazole (Rexulti)+ADT-treated patients versus 3% for placebo+ADT-treated patients. The incidence of akathisia events for Brexpiprazole (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 extrapyramidal symptoms (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 Brexpiprazole (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 Brexpiprazole (Rexulti)+ADT-treated patients versus placebo+ADT 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 Brexpiprazole (Rexulti)-treated patients versus 4% for placebo-treated patients. The incidence of akathisia events for Brexpiprazole (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 extrapyramidal symptoms (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 Brexpiprazole (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 Brexpiprazole (Rexulti)-treated patients versus placebo for the BARS (2% versus 1%) and the SAS (7% versus 5%).
Agitation Associated with Dementia Due to Alzheimer's Disease: The incidence of reported EPS-related adverse reactions, excluding akathisia, was 3% for Brexpiprazole (Rexulti)-treated patients versus 2% for placebo-treated patients. The incidence of akathisia events for Brexpiprazole (Rexulti)-treated patients was 1% versus 0% for placebo-treated patients.
In the 12-week placebo-controlled, fixed-dose studies in agitation associated with dementia due to Alzheimer's disease, 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 Brexpiprazole (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 Brexpiprazole (Rexulti)-treated patients versus placebo for the SAS (6% versus 2%).
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 Brexpiprazole (Rexulti): Other adverse reactions (≥1% frequency and greater than placebo) within the short-term, placebo-controlled trials in patients with MDD and schizophrenia are shown as follows. 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.
Investigations: Blood Prolactin Increased.
Musculoskeletal and Connective Tissue Disorders: Myalgia.
Psychiatric Disorders: Abnormal Dreams.
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis.
Pediatric Patients (13 to 17 years of age): In an on-going, 2 year, open-label study in pediatric patients 13 to 17 years of age with schizophrenia, in which safety was assessed in 194 patients of which 140 received Brexpiprazole (Rexulti) for at least 6 months. Adverse reactions reported in clinical studies for this age group were generally similar to those observed in adult patients.
Postmarketing Experience: The following adverse reaction has been identified during post-approval use of Brexpiprazole (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.