Brexi 0.5

Indicated for schizophrenia, Indicated as adjunctive treatment for major depressive disorder

May take with or without food

Schizophrenia Indicated for schizophrenia Recommended starting dose: 1 mg PO qDay on Days 1 through 4 Recommended target dose: 2-4 mg PO qDay; titrate to 2 mg qDay on Days 5 through 7, and then to 4 mg/day on Day 8 based on the patient’s clinical response and tolerability Not to exceed 4 mg/day Periodically reassess to determine the continued need and appropriate dose Depression Indicated as adjunctive treatment for major depressive disorder Recommended starting dose: 0.5 mg or 1 mg PO qDay Recommended target dose: 2 mg PO qDay; at weekly intervals, titrate to 1 mg/day, and then up to 2 mg/day Titrate according to clinical response and tolerability Not to exceed 3 mg/day Periodically reassess to determine the continued need and appropriate dose Hepatic impairment Moderate-to-severe hepatic impairment (Child-Pugh ?7) MDD: Not to exceed 2 mg/day Schizophrenia: Not to exceed 3 mg/day

Renal impairment Moderate, severe, or ESRD (CrCl <60 mL/min) MDD: Not to exceed 2 mg/day Schizophrenia: Not to exceed 3 mg/day

Hypersensitivity; reactions have included rash, facial swelling, urticaria, and angioedema

Serotonin-dopamine activity modulator (SDAM) that acts as a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors

Increased mortality in elderly patients with dementia-related psychosis; in placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks), including fatalities, compared with placebo Suicidal thoughts and behaviors reported in children, adolescents, and young adults who are taking antidepressant drugs Potentially fatal neuroleptic malignant syndrome (NMS) reported in association with administration of antipsychotic drugs; if NMS is suspected, immediately discontinue therapy and provide intensive symptomatic treatment and monitoring Potentially irreversible, involuntary, dyskinetic movements (ie, tardive dyskinesia) reported with antipsychotic drugs; incidence highest in elderly persons, especially elderly women Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus (including extreme cases associated with ketoacidosis or hyperosmolar coma or death), dyslipidemia, and body weight gain; May cause leukopenia, neutropenia, and agranulocytosis; monitor and discontinue Orthostatic hypotension or syncope may occur (rare); generally, the risk is greatest during initial dose titration and when increasing the dose; orthostatic vital signs should be monitored in patients who are vulnerable to hypotension, (e.g., elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medication, patients with known cardiovascular disease, and patients with cerebrovascular disease) May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Caution with a history of seizures or with conditions/drugs that potentially lower the seizure threshold Lactation Unknown if distributed in human breast milk

>10% Akathisia (4-14%) 1-10% Headache (4-9%) Weight increased (3-8%) Nasopharyngitis (1-7%) Extrapyramidal symptoms, excluding akathisia (5-6%) Somnolence (4-6%) Dyspepsia (2-6%) Constipation (1-6%) Tremor (2-5%) Fatigue/sedation (2-5%) Dizziness (1-5%) Increased CPK blood levels (2-4%) Decreased cortisol levels (2-4%) Anxiety (2-4%) Restlessness (2-4%) Increased appetite (2-3%) Diarrhea (1-3%) Frequency Unknown Dystonia

Pregnancy Adequate and well-controlled studies have not been conducted with brexpiprazole in pregnant women to inform drug-associated risks; however, neonates whose mothers are exposed to antipsychotic drugs, like brexpiprazole, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms (eg, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) Animal reproduction studies No teratogenicity was observed with oral administration of brexpiprazole to pregnant rats and rabbits during organogenesis at doses up to 73 and 146 times, respectively, of maximum recommended human dose (MRHD) of 4 mg/day on a mg/m² basis However, when pregnant rats were administered brexpiprazole during the period of organogenesis through lactation, the number of perinatal deaths of pups was increased at 73 times the MRHD Lactation Unknown if distributed in human breast milk Present in rat milk The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition