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. |
| Molecular Weight | 410.49 |
| 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 | Limited human data; animal studies show developmental toxicity. Use only if benefit outweighs risk. |
| 2nd trimester | May cause extrapyramidal symptoms and withdrawal in neonates. Monitor for abnormal muscle movements. |
| 3rd trimester | Risk of neonatal extrapyramidal symptoms, agitation, and feeding difficulties. Consider gradual discontinuation before delivery. |
Clinical note
Comprehensive clinical and safety monograph for RISPERDAL CONSTA (RISPERDAL CONSTA).
| Placental transfer | Crosses the placenta; fetal concentrations approximately 50-100% of maternal levels. Transporter-mediated transfer (P-gp). |
| Breastfeeding | Excreted in breast milk in low amounts; infant exposure estimated at <5% maternal weight-adjusted dose. Monitor infant for sedation, irritability, and feeding problems. Consider alternative if available. |
■ 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 | Neuroleptic Malignant Syndrome (NMS), Tardive Dyskinesia, Stroke and transient ischemic attacks in elderly patients with dementia-related psychosis, Hyperglycemia and diabetes mellitus, Hyperprolactinemia, Orthostatic hypotension and syncope, Seizures, Leukopenia, neutropenia, and agranulocytosis, QT prolongation, Priapism |
Known hypersensitivity to risperidone or any componentConcomitant use with drugs that prolong QT interval (e.g., Class IA/III antiarrhythmics, certain antipsychotics)
| 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 |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Avoid grapefruit juice as it may increase plasma concentrations of risperidone. No other known food or dietary restrictions. |
| Clinical Pearls | Risperdal Consta is a long-acting injectable atypical antipsychotic requiring oral risperidone coverage for the first 3 weeks. Administer only into gluteal muscle every 2 weeks; do not substitute on a milligram-to-milligram basis with oral risperidone. Monitor for orthostatic hypotension, extrapyramidal symptoms, and weight gain. Avoid in elderly with dementia-related psychosis due to increased mortality risk. |
| Patient Advice | You will receive an injection every 2 weeks into your buttock muscle. · Keep taking your oral medication for the first 3 weeks after starting the injection. · Do not stop your injection without talking to your doctor; missing doses can cause return of symptoms. · Rare but serious side effects include neuroleptic malignant syndrome (fever, muscle stiffness, confusion) and tardive dyskinesia (uncontrolled movements). · May cause dizziness when standing up, especially early in treatment. Rise slowly. · Avoid alcohol and grapefruit juice during treatment. |