UZEDY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UZEDY (UZEDY).
Atypical antipsychotic; antagonist at dopamine D2 and serotonin 5-HT1A/5-HT2A receptors; partial agonist at serotonin 5-HT1A receptors
| Metabolism | Substrate of CYP3A4 and CYP1A2; metabolized to paliperidone |
| Excretion | Primarily renal: 80% as metabolites, 1% unchanged. Biliary/fecal: 20%. |
| Half-life | Terminal half-life approximately 30 days (range 23–37 days) after subcutaneous injection, supporting monthly dosing. |
| Protein binding | ~98% bound primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | Vd/F ~1000 L (approximately 14 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Subcutaneous: 100% (prodrug risperidone ISM). |
| Onset of Action | Subcutaneous: 3–4 weeks to steady-state; clinical effect observed within 2–3 weeks. |
| Duration of Action | Therapeutic effect lasts 4–5 weeks after single subcutaneous injection; dosing interval is monthly. |
UZEDY (risperidone) extended-release injectable suspension: 75 mg, 100 mg, 150 mg, or 200 mg IM gluteal injection every 2 weeks after a single oral dose of 2 mg risperidone for 2 days; or 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, or 150 mg IM every 4 weeks after oral overlap for 2 days. Oral risperidone may be omitted if patient is stable on oral risperidone 2 mg/day.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | CrCl <30 mL/min: Not recommended. CrCl 30-49 mL/min: Administer 25 mg IM every 4 weeks; no dose >25 mg. CrCl ≥50 mL/min: No adjustment. |
| Liver impairment | Child-Pugh Class A or B: No dosage adjustment required. Child-Pugh Class C: Not studied; use caution. |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | For geriatric patients, initiate with 25 mg IM every 4 weeks; maximum dose 50 mg IM every 4 weeks. Consider lower starting doses and slower titration. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UZEDY (UZEDY).
| Breastfeeding | Risperidone and its active metabolite 9-hydroxyrisperidone are excreted in breast milk; the milk-to-plasma ratio is approximately 0.5 for risperidone and 0.24 for 9-hydroxyrisperidone. Multiple studies indicate infant doses are low (relative infant dose <10% of weight-adjusted maternal dose). Monitor infant for sedation, irritability, and poor feeding. Breastfeeding is generally considered acceptable with caution. |
| Teratogenic Risk | UZEDY (risperidone) is not associated with major congenital malformations in the first trimester based on limited data, but may increase risk for extrapyramidal symptoms and withdrawal symptoms in neonates after third trimester exposure. No specific trimester risks are established; avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to risperidone, paliperidone, or any component of the formulation"]
| Precautions | ["Cerebrovascular adverse reactions in elderly patients with dementia","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Metabolic changes (hyperglycemia, dyslipidemia, weight gain)","Leukopenia, neutropenia, agranulocytosis","Orthostatic hypotension and syncope","Seizures","Potential for cognitive and motor impairment","Dysphagia","Body temperature regulation disruption"] |
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| Fetal Monitoring | Monitor maternal psychiatric status, weight gain, blood glucose, and prolactin levels. For neonates exposed in third trimester, observe for symptoms of extrapyramidal toxicity (e.g., hypertonia, tremor) or withdrawal (e.g., agitation, respiratory distress). |
| Fertility Effects | Risperidone can elevate prolactin levels via dopamine D2 blockade, potentially causing menstrual irregularities, anovulation, and galactorrhea, thereby reducing fertility. Effects are reversible upon dose reduction or discontinuation. |