CV: cerebrovascular adverse reactions (↑ in elderly patients with dementia-related psychoses), orthostatic hypotension/syncope.
EENT: blurred vision.
Endo: hyperglycemia/diabetes.
GI: abdominal pain, constipation, diarrhea, dry mouth, dysphagia, excess salivation, flatulence.
Hemat: agranulocytosis, leukopenia, neutropenia.
Metab: ↑ weight, ↑ appetite, dyslipidemia.
Neuro: akathisia, abnormal dreams, dizziness, drowsiness, dystonia, extrapyramidal symptoms, headache, NEUROLEPTIC MALIGNANT SYNDROME, restlessness, SEIZURES, tardive dyskinesia, tremor, urges (eating, gambling, sexual, shopping).
Misc: body temperature dysregulation, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS).
Schizophrenia
- PO (Adults): 1 mg once daily on Days 14, then ↑ to 2 mg once daily on Days 57, then ↑ to 4 mg once daily on Day 8 (not to exceed 4 mg once daily). Known CYP2D6 poor metabolizers: use 50% of the usual dose. Concurrent use of strong CYP2D6 inhibitors (schizophrenia only) or CYP3A4 inhibitors: use 50% of the usual dose; Concurrent use of strong/moderate CYP2D6 inhibitors AND strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Known CYP2D6 poor metabolizer taking concurrent strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Concurrent use of strong CYP3A4 inducers: double usual dose over 12 wk; titrate by clinical response.
- PO (Children 1317 yr): 0.5 mg once daily on Days 14, then ↑ to 1 mg once daily on Days 57, then ↑ to 2 mg once daily on Day 8. May ↑ dose by 1 mg/day on weekly basis (not to exceed 4 mg once daily). Known CYP2D6 poor metabolizers: use 50% of the usual dose. Concurrent use of strong CYP2D6 inhibitors (schizophrenia only) or CYP3A4 inhibitors: use 50% of the usual dose; Concurrent use of strong/moderate CYP2D6 inhibitors AND strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Known CYP2D6 poor metabolizer taking concurrent strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Concurrent use of strong CYP3A4 inducers: double usual dose over 12 wk; titrate by clinical response.
Renal Impairment
- PO (Adults and Children 1317 yr): Moderate/severe/end-stage renal impairment [CCr <60 mL/min]: maximum daily dose should not exceed 3 mg.
Hepatic Impairment
- (Adults and Children 1317 yr): Moderate to severe hepatic impairment [Child-Pugh score ≥7]: maximum daily dose should not exceed 3 mg.
Major Depressive Disorder
- PO (Adults): 0.5 or 1 mg once daily initially, may be ↑ to 2 mg once daily (not to exceed 3 mg once daily); Known CYP2D6 poor metabolizers: use 50% of the usual dose. Concurrent use of strong CYP2D6 inhibitors (schizophrenia only) or CYP3A4 inhibitors: use 50% of the usual dose; Concurrent use of strong/moderate CYP2D6 inhibitors AND strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Known CYP2D6 poor metabolizer taking concurrent strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Concurrent use of strong CYP3A4 inducers: double usual dose over 12 wk; titrate by clinical response.
Renal Impairment
- PO (Adults): Moderate/severe/end-stage renal impairment [CCr <60 mL/min]: maximum daily dose should not exceed 2 mg.
Hepatic Impairment
- PO (Adults): Moderate to severe hepatic impairment [Child-Pugh score ≥7]: maximum daily dose should not exceed 2 mg.
Agitation Associated with Dementia Due to Alzheimers Disease
- PO (Adults): 0.5 mg once daily on Days 17, then ↑ to 1 mg once daily on Days 814, then ↑ to 2 mg once daily on Day 15. May ↑ to 3 mg once daily after ≥14 days based on clinical response and tolerability. Known CYP2D6 poor metabolizers: use 50% of the usual dose. Concurrent use of strong CYP2D6 inhibitors (schizophrenia only) or CYP3A4 inhibitors: use 50% of the usual dose; Concurrent use of strong/moderate CYP2D6 inhibitors AND strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Known CYP2D6 poor metabolizer taking concurrent strong/moderate CYP3A4 inhibitors: use 25% of the usual dose; Concurrent use of strong CYP3A4 inducers: double usual dose over 12 wk; titrate by clinical response.
Renal Impairment
- PO (Adults): Moderate/severe/end-stage renal impairment [CCr <60 mL/min]: maximum daily dose should not exceed 2 mg.
Hepatic Impairment
- PO (Adults): Moderate to severe hepatic impairment [Child-Pugh score ≥7]: maximum daily dose should not exceed 2 mg.
Therapeutic Classification: antipsychotics, antidepressants
Pharmacologic Classification: serotonin-dopamine activity modulators (SDAM)
Absorption: Well absorbed (95%) following oral administration.
Distribution: Displays extravascular distribution.
Protein Binding: >99%.
Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 and CYP2D6 isoenzymes; the CYP2D6 enzyme system exhibits genetic polymorphism (7% of population may be poor metabolizers and may have significantly ↑ brexpiprazole concentrations and an ↑ risk of adverse effects). 25% excreted in urine (<1% unchanged), 46% in feces (14% unchanged).
Half-life: 91 hr.
(improvement in symptoms)