RISPERDAL CONSTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RISPERDAL CONSTA (RISPERDAL CONSTA).
Risperidone is an atypical antipsychotic with high affinity for serotonin 5-HT2A and dopamine D2 receptors. It also binds to alpha1-adrenergic, alpha2-adrenergic, and histamine H1 receptors, with low affinity for muscarinic receptors. The combination of 5-HT2A and D2 antagonism is thought to improve negative symptoms and reduce extrapyramidal side effects.
| Metabolism | Risperidone is extensively metabolized in the liver by CYP2D6 to the active metabolite 9-hydroxyrisperidone (paliperidone). CYP3A4 and CYP2D6 are involved in minor pathways. The parent drug and metabolite are equally active. |
| Excretion | Risperidone and its active metabolite 9-hydroxyrisperidone are primarily excreted renally (70%), with 14% excreted in feces. The remainder is eliminated via biliary and metabolic pathways. |
| Half-life | The terminal elimination half-life of risperidone is approximately 20 hours for CYP2D6 extensive metabolizers and 24 hours for poor metabolizers (accounting for both risperidone and 9-hydroxyrisperidone). The half-life of the active moiety is about 20 hours, allowing for biweekly dosing of the long-acting injection. |
| Protein binding | Risperidone is approximately 90% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein); 9-hydroxyrisperidone is 77% protein bound. |
| Volume of Distribution | The volume of distribution (Vd) for risperidone is approximately 1-2 L/kg, indicating extensive tissue distribution. The Vd for 9-hydroxyrisperidone is 0.5-1 L/kg. |
| Bioavailability | Oral risperidone has a bioavailability of 70% (first-pass metabolism). The long-acting injectable (Risperdal Consta) has an absolute bioavailability of 100% following intramuscular administration. |
| Onset of Action | The long-acting injectable (Risperdal Consta) requires 3 weeks to achieve therapeutic plasma concentrations after the first injection; during this period, oral antipsychotic supplementation is needed. The onset of clinical effect (e.g., reduction in psychotic symptoms) is typically observed within 1-2 weeks after initiating oral risperidone. |
| Duration of Action | The therapeutic effect of Risperdal Consta after intramuscular injection lasts for 2 weeks (maintenance dosing interval). The pharmacokinetic profile supports biweekly dosing, with the active moiety detectable for up to 4-6 weeks after the last injection. |
| Action Class | Atypical Antipsychotics |
| Brand Substitutes | Restonorm 25 Injection, Restonorm 50 Injection |
25 mg intramuscular every 2 weeks; may increase to 37.5 mg or 50 mg after 4 weeks if needed.
| Dosage form | POWDER |
| Renal impairment | Contraindicated if creatinine clearance < 20 mL/min; for GFR 20-49 mL/min, reduce dose to 25 mg every 2 weeks. |
| Liver impairment | Child-Pugh Class A or B: 25 mg every 2 weeks; Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for patients < 18 years. |
| Geriatric use | Initiate at 25 mg every 2 weeks; consider lower doses due to increased sensitivity; monitor for orthostatic hypotension and extrapyramidal symptoms. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RISPERDAL CONSTA (RISPERDAL CONSTA).
| Breastfeeding | Risperidone and 9-hydroxyrisperidone are excreted into breast milk. M/P ratio not well established; relative infant dose approximately 4-10% of maternal weight-adjusted dose. Monitor infant for sedation, irritability, and poor feeding. Use caution, especially in preterm infants. |
| Teratogenic Risk | First trimester: Limited data, but risperidone is not a major teratogen; risk of malformations similar to background. Second/third trimester: Risk of extrapyramidal symptoms and withdrawal in neonates after late exposure. Not recommended 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. Risperdal Consta is not approved for the treatment of dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to risperidone, paliperidone, or any component of the formulation"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Cerebrovascular adverse events (including stroke) in elderly dementia patients","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Hyperglycemia and diabetes mellitus","Hyperprolactinemia","Orthostatic hypotension","Leukopenia, neutropenia, and agranulocytosis","QT prolongation","Seizures","Priapism","Body temperature regulation disruption","Dysphagia","Potential for cognitive and motor impairment"] |
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| Fetal Monitoring | Monitor maternal weight, glucose, prolactin levels. Assess fetal growth via ultrasound if prolonged use. Neonatal monitoring for extrapyramidal symptoms and withdrawal for 3-5 days post-delivery. |
| Fertility Effects | Risperidone may elevate prolactin levels, causing amenorrhea, galactorrhea, and anovulation. Reversible upon dose reduction or discontinuation. Impact on spermatogenesis not well studied. |