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. |
| Molecular Weight | 410.48 |
| Action Class | Atypical Antipsychotic |
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 | Risperidone crosses the placenta. There are no adequate and well-controlled studies in pregnant women. UZEDY should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms. |
| 2nd trimester | Same as first trimester. |
| 3rd trimester | Same as first trimester. Additionally, monitor neonates for extrapyramidal and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for UZEDY (UZEDY).
| Placental transfer | Risperidone crosses the placenta. Evidence based on human data shows measurable levels in cord blood. |
| Breastfeeding | Risperidone is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. |
■ 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.
| Common Effects | Extrapyramidal symptoms (dystonia, akathisia, parkinsonism), Somnolence and sedation, Insomnia, Headache, Dizziness, Nausea and vomiting, Constipation, Dyspepsia, Weight gain, Increased appetite, Fatigue, Anxiety, Nasal congestion, Rash, Dry mouth, Salivary hypersecretion, Blurred vision |
| Serious Effects | Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia, Stroke and transient ischemic attacks in elderly patients with dementia-related psychosis, QT prolongation and risk of torsades de pointes, Venous thromboembolism, Seizures, Hyperprolactinemia leading to galactorrhea, amenorrhea, gynecomastia, and sexual dysfunction, Metabolic changes including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain, Leukopenia, neutropenia, and agranulocytosis, Orthostatic hypotension and syncope, Priapism, Body temperature dysregulation |
Known hypersensitivity to risperidone or any component of UZEDY
| Precautions |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| 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 |
| Food/Dietary | No clinically significant food interactions have been reported. Grapefruit and grapefruit juice are not expected to affect risperidone levels. Avoid excessive alcohol consumption as it may increase sedative effects. |
| Clinical Pearls | Uzedy (risperidone) is a long-acting injectable atypical antipsychotic. Due to its unique extended-release microsphere formulation, it requires reconstitution with the provided diluent and must be administered immediately after reconstitution. Do not substitute any components. The gluteal muscle is the preferred injection site; rotate between left and right. Observe for post-injection syndrome (somnolence, dysarthria, hypotension) for 3 hours post-injection. Monitor for extrapyramidal symptoms, hyperglycemia, weight gain, and QTc prolongation. Dose adjustments may be needed in renal or hepatic impairment. |
| Patient Advice | Uzedy is a long-acting injection given every 2 weeks by a healthcare professional. · Do not try to self-inject or dispose of the medication; it must be administered by a trained provider. · Common side effects include drowsiness, dizziness, weight gain, and movement problems like tremors or stiffness. · Avoid alcohol and driving until you know how this medication affects you. · Report any new or worsening symptoms of depression, suicidal thoughts, or impulsive behavior. · If pregnant or planning to become pregnant, inform your doctor immediately. |