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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REXULTI (REXULTI).
| Breastfeeding | Brexpiprazole is excreted in human breast milk. The milk-to-plasma (M/P) ratio is not established. A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Infants exposed to brexpiprazole through breast milk should be monitored for adverse effects such as sedation, irritability, and poor feeding. |
| 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. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis (not approved for dementia-related psychosis).
| Serious Effects |
Hypersensitivity to brexpiprazole or any components of the formulation.
| 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. |
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| 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. |