REXULTI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REXULTI (REXULTI).
Partial agonist at D2 and 5-HT1A receptors; antagonist at 5-HT2A and α1B/α2C adrenergic receptors.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; also metabolized by CYP2C8 and aldehyde oxidase. |
| Excretion | Approximately 25% of the dose is excreted in urine as unchanged drug and metabolites; about 54% is excreted in feces. Renal excretion of unchanged drug is minor (<1%). |
| Half-life | Terminal elimination half-life is approximately 19–23 days for brexpiprazole and its major metabolite DM-3411, requiring up to 2–3 months to reach steady state. |
| Protein binding | >99% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd/F is approximately 1.56 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: Absolute bioavailability is approximately 95% (tablet form). |
| Onset of Action | Oral: Clinical effects may be observed within 2–4 weeks; full therapeutic response may take several weeks. |
| Duration of Action | Due to long half-life, effects persist for weeks after discontinuation; taper recommended to avoid withdrawal. |
| Molecular Weight | 422.48 |
| Action Class | Atypical Antipsychotic |
2 mg orally once daily initially; increase to 4 mg once daily no sooner than week 2; target dose 4 mg once daily; range 2-4 mg once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for GFR ≥ 15 mL/min; not recommended in ESRD (eGFR < 15 mL/min). |
| Liver impairment | Child-Pugh A or B: no adjustment; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for patients under 18 years of age. |
| Geriatric use | Initiate at 2 mg once daily; maximum 4 mg once daily; monitor for orthostatic hypotension and sedation. |
| 1st trimester | Limited human data; animal studies show developmental toxicity. Use only if potential benefit justifies risk. |
| 2nd trimester | No adequate human studies; consider fetal effects of dopamine antagonism. Use with caution. |
| 3rd trimester | Risk of extrapyramidal symptoms and/or withdrawal in neonate with late third trimester exposure. |
Clinical note
Comprehensive clinical and safety monograph for REXULTI (REXULTI).
| Placental transfer | Expected to cross placenta based on molecular weight and lipophilicity; specific data not available. |
| Breastfeeding | Present in rat milk; unknown if excreted in human milk. Consider developmental benefits of breastfeeding vs. potential adverse effects. Monitor infant for sedation, irritability, and weight gain. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis (not approved for dementia-related psychosis).
| Common Effects | Weight gain, Akathisia, Somnolence, Sedation, Nausea, Constipation, Headache, Insomnia, Extrapyramidal symptoms, Increased appetite |
| Serious Effects | Increased mortality in elderly patients with dementia-related psychosis, Suicidal thoughts or behaviors, Neuroleptic malignant syndrome, Tardive dyskinesia, Stroke and transient ischemic attacks in elderly with dementia, Hyperglycemia and diabetes mellitus, Leukopenia, neutropenia, and agranulocytosis, Orthostatic hypotension and syncope, Seizures, Body temperature dysregulation |
Hypersensitivity to brexpiprazole or any excipients
| Precautions | Suicidal thoughts and behaviors; neuroleptic malignant syndrome; tardive dyskinesia; metabolic changes (hyperglycemia, dyslipidemia, weight gain); orthostatic hypotension; seizures; leukopenia/neutropenia; cognitive and motor impairment; dysphagia; body temperature dysregulation; concomitant use of opioids. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | REXULTI (brexpiprazole) is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, brexpiprazole caused developmental toxicity (including fetal malformations, reduced fetal weight, and increased fetal death) at doses less than the maximum recommended human dose (MRHD) based on mg/m². In the first trimester, there is a potential risk of major malformations, but data are insufficient. In the second and third trimesters, antipsychotic exposure may cause extrapyramidal and/or withdrawal symptoms in neonates. Use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor pregnant women for worsening of psychiatric symptoms. Perform baseline and follow-up fetal ultrasound if exposure occurs during pregnancy. Monitor neonates for extrapyramidal symptoms, withdrawal, or excessive sedation after delivery. Monitor for gestational diabetes and weight gain. |
| Fertility Effects | In animal studies, brexpiprazole did not impair fertility in rats. However, hyperprolactinemia associated with antipsychotics may reduce fertility in humans due to inhibition of gonadotropin-releasing hormone. Clinical significance is unknown. |
| Food/Dietary | REXULTI can be taken with or without food. No specific food restrictions. However, grapefruit juice may increase brexpiprazole exposure; avoid concurrent consumption. Alcohol may potentiate CNS depression; avoid use. |
| Clinical Pearls | REXULTI (brexpiprazole) is a partial agonist at D2 and 5-HT1A receptors and an antagonist at 5-HT2A, similar to aripiprazole but with higher affinity. It has lower intrinsic activity at D2, which may reduce the risk of akathisia and activation. Dosing adjustments: reduce dose in moderate-to-severe hepatic impairment (Child-Pugh score ≥7) or moderate-to-severe renal impairment (CrCl <60 mL/min). For schizophrenia, start at 1 mg/day, titrate weekly to target 2-4 mg/day; max 4 mg/day. For MDD adjunctive, start at 0.5-1 mg/day, titrate to 1-3 mg/day; max 3 mg/day. Monitor for metabolic changes (weight, glucose, lipids) and extrapyramidal symptoms. Avoid abrupt discontinuation; taper gradually. |
| Patient Advice | Take REXULTI once daily with or without food; swallowing whole tablets. · Do not crush, chew, or split tablets. · Avoid alcohol while taking REXULTI. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Report any unusual muscle movements, especially of face, tongue, or jaw. · Notify doctor of any thoughts of suicide or worsening depression, especially early in treatment. · May cause weight gain and changes in blood sugar or cholesterol; regular monitoring is needed. · Do not stop abruptly; your doctor will guide you on tapering. · If pregnant or planning to become pregnant, discuss risks; there is a pregnancy registry. |