BREXPIPRAZOLE
Clinical safety rating: safe
Animal studies have demonstrated safety
Partial agonist at dopamine D2 and serotonin 5-HT1A receptors; antagonist at serotonin 5-HT2A receptors.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; minor pathways via CYP1A2 and CYP2C8. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2D6; ~25% renal excretion (mostly as metabolites), ~60% fecal excretion (mostly as metabolites). |
| Half-life | 91 hours (range 70–120 hours) for the parent drug; repeated dosing leads to steady state in ~3–4 weeks. The active metabolite DM-3411 has a half-life of ~86 hours. |
| Protein binding | >99% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | ~1.56 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: ~95% (high bioavailability, but food increases AUC by ~30% and Cmax by ~40%). |
| Onset of Action | Oral: Symptomatic improvement may begin within 1–2 weeks, but full therapeutic effect typically requires 4–6 weeks. |
| Duration of Action | Due to the long half-life, once-daily dosing maintains therapeutic concentrations; effects persist for several days after discontinuation. |
Oral: 1 mg once daily initially, titrate to 2 mg once daily after 3-7 days, then to 4 mg once daily based on response; maximum 4 mg once daily.
| Dosage form | TABLET |
| Renal impairment | For severe renal impairment (eGFR 15-29 mL/min/1.73 m²): maximum dose 3 mg once daily. For end-stage renal disease (eGFR <15 mL/min/1.73 m²): not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: maximum dose 2 mg once daily; Child-Pugh Class C: not recommended. |
| Pediatric use | Children (10-17 years): initial 0.5 mg once daily, titrate to target 1-2 mg once daily; maximum 4 mg once daily. Weight-based: no specific weight-based guidelines; dosing based on clinical response. |
| Geriatric use | No specific dose adjustment required based solely on age, but caution due to increased sensitivity; initiate at 0.5-1 mg once daily and titrate slowly, with maximum 4 mg once daily. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 or CYP2D6 inhibitors require dose adjustment May cause suicidal thoughts and metabolic changes including weight gain and dyslipidemia.
| Breastfeeding | No data on presence in human milk or effects on breastfed infant; M/P ratio unknown. Breastfeeding is not recommended due to potential for adverse effects on infant development. |
| Teratogenic Risk | Pregnancy category C. First trimester: Limited human data; animal studies show fetal developmental toxicity at doses similar to human therapeutic doses. Second and third trimesters: Risk of extrapyramidal and/or withdrawal symptoms in neonates after late third trimester exposure; no specific structural malformations identified. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
| Common Effects | adjunct for depression |
| Serious Effects |
Known hypersensitivity to brexpiprazole or any components of the formulation.
| Precautions | Increased mortality in elderly patients with dementia-related psychosis; suicidal thoughts and behaviors; neuroleptic malignant syndrome; tardive dyskinesia; metabolic changes (hyperglycemia, dyslipidemia, weight gain); orthostatic hypotension; seizures; body temperature dysregulation; dysphagia; leukopenia/neutropenia/agranulocytosis; cognitive and motor impairment; hyperprolactinemia. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase brexpiprazole levels. No significant food interactions otherwise. May be taken without regard to meals. |
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| Fetal Monitoring | Monitor maternal mental status, vital signs, and weight gain; fetal ultrasound for growth and anatomy; neonatal monitoring for extrapyramidal symptoms, sedation, and feeding difficulties after delivery. |
| Fertility Effects | In animal studies, reversible decreases in fertility and mating indices in males and females at doses similar to human exposure. Human data limited; potential for hormonal disruption. |
| Clinical Pearls | Brexpiprazole has a lower propensity for akathisia compared to aripiprazole due to partial agonism at 5-HT1A and antagonism at 5-HT2A receptors. Monitor for weight gain and metabolic changes; consider baseline and periodic monitoring of glucose and lipids. Avoid use in dementia-related psychosis due to increased mortality risk. Titrate slowly to minimize orthostatic hypotension. |
| Patient Advice | Take once daily with or without food. · Do not drive or operate heavy machinery until you know how this medication affects you. · Report any restlessness, muscle stiffness, fever, or confusion immediately. · Avoid alcohol and grapefruit products while taking this medication. · Do not stop taking abruptly; consult your doctor before discontinuing. · Inform your doctor of all medications you are taking, especially antidepressants and blood pressure medications. |