Indicated for:

Adjunctive Treatment of Major Depressive Disorder:

• Adjunctive treatment of major depressive disorder (MDD) in adults.

Treatment of Schizophrenia:

• Treatment of schizophrenia in adults and pediatric patients ages 13 years and older.

For patients with moderate to severe hepatic impairment (Child-Pugh score ≥7), the maximum recommended dosage is 2 mg once daily for patients with MDD, and 3 mg once daily for patients with schizophrenia.

For patients with moderate, severe or end-stage renal impairment (creatinine clearance CL_cr<60 mL/minute), the maximum recommended dosage is 2 mg once daily for patients with MDD and 3 mg once daily for patients with schizophrenia.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. REXULTI is not approved for the treatment of patients with dementia-related psychosis.

Antidepressants increased the risk of suicidal thoughts and behaviors in patients aged 24 years and younger in short-term studies. Monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of REXULTI have not been established in pediatric patients with MDD.

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs.

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs.

Atypical antipsychotic drugs, including REXULTI, have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain.

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.

Post-marketing case reports suggest that patients can experience intense urges, particularly for gambling, and the inability to control these urges while taking REXULTI. Other compulsive urges, reported less frequently, include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or intense gambling urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or other urges while being treated with REXULTI.

Leukopenia and neutropenia have been reported during treatment with antipsychotic agents. Agranulocytosis (including fatal cases) has been reported with other agents in this class. Possible risk factors for leukopenia and neutropenia include pre-existing low white blood cell count (WBC) or absolute neutrophil count (ANC) and history of drug-induced leukopenia or neutropenia.

Atypical antipsychotics cause orthostatic hypotension and syncope. Generally, the risk is greatest during initial dose titration and when increasing the dose. Antipsychotics, including REXULTI, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

Like other antipsychotic drugs, REXULTI may cause seizures.

Atypical antipsychotics may disrupt the body’s ability to reduce core body temperature. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use REXULTI with caution in patients who may experience these conditions.

REXULTI, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills.

Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates whose mothers were exposed to antipsychotic drugs during the third trimester of pregnancy.

Dosage adjustment is recommended in known CYP2D6 poor metabolizers, because these patients have higher brexpiprazole concentrations than normal metabolizers of CYP2D6.

Concomitant use of REXULTI with strong CYP2D6 inhibitors (e.g.,paroxetine, fluoxetine, quinidine) increased the exposure of brexpiprazole compared to the use of REXULTI alone.

Concomitant use of REXULTI with strong CYP3A4 inhibitors (e.g.,itraconazole, clarithromycin, ketoconazole) increased the exposure of brexpiprazole compared to the use of REXULTI alone.

Concomitant use of REXULTI and a strong CYP3A4 inducer (e,g, rifampin, St. John’s wort) decreased the exposure of brexpiprazole compared to the use of REXULTI alone.

Adequate and well-controlled studies have not been conducted with REXULTI in pregnant women to inform drug-associated risks. However, neonates whose mothers are exposed to antipsychotic drugs, like REXULTI, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms. Animal studies: perinatal deaths.

Lactation studies have not been conducted to assess the presence of brexpiprazole in human milk, the effects of brexpiprazole on the breastfed infant, or the effects of brexpiprazole on milk production. Brexpiprazole is present in rat milk.

GoToSource

• Attention-deficit/hyperactivity disorder, post-traumatic stress disorder, bipolar depression, mania and agitation associated with dementia of alzheimer’s type. GoToSource

• Adjunctive therapy for sleep disturbances. GoToSource

• Use in patients under the age of 13 and over 65 years of age. GoToSource

⚠️  Increased risk of side effects and and higher systemic concentrations in patients with CYP2D6 gene variant.

Increased risk of mortality in elderly patients with dementia-related psychosis, cerebrovascular events including stroke, worsening suicidal thoughts and behaviors, neuroleptic malignant syndrome (life-threatening reaction to antipsychotic drugs), exacerbation of metabolic parameters, orthostatic hypotension (excessive fall in blood pressure when upright position is assumed), dysregulation of body temperature, seizures, motor/cognitive impairment, neutropenia, leukopenia and agranulocytosis (low white blood count). GoToSource

Hyperprolactinemia (high level of prolactin a hormone secreted by pituitary gland) and increased glycosylated hemoglobin level (increased blood sugar). GoToSource

Akathisia (movement disorder), weight gain, constipation, fatigue, sleepiness, headache, tremor, dizziness, anxiety, restlessness, sedation, dyspepsia (indigestion), diarrhea, increased blood creatine phosphokinase (indicates stress or injury to heart or other muscles), extrapyramidal symptoms (drug-induced movement disorders) and dystonic reactions (neurological movement disorder). GoToSource

Lawsuits filed for impulse-control disorders, stroke, death, tardive dyskinesia, neuroleptic malignant syndrome and seizures.