RISPERDAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RISPERDAL (RISPERDAL).
Risperidone is a benzisoxazole atypical antipsychotic that antagonizes dopamine D2 and serotonin 5-HT2A receptors. It also blocks alpha1-adrenergic, alpha2-adrenergic, and histamine H1 receptors.
| Metabolism | Risperidone is extensively metabolized by cytochrome P450 2D6 (CYP2D6) to its active metabolite, 9-hydroxyrisperidone (paliperidone). A minor pathway involves CYP3A4 and CYP3A5. The metabolite is further metabolized via N-dealkylation and oxidative pathways. |
| Excretion | Renal: 70% (30% as unchanged drug, 40% as metabolites), Fecal/Biliary: 14% |
| Half-life | 20 hours (parent drug), 23 hours (active metabolite 9-hydroxyrisperidone). Steady state reached in 5-6 days. Extended in elderly and hepatic/renal impairment. |
| Protein binding | 90% (albumin and alpha-1-acid glycoprotein). Active metabolite 77% bound. |
| Volume of Distribution | 1-2 L/kg. Large Vd indicates extensive tissue distribution and penetration into CNS. |
| Bioavailability | Oral: 70% (with extensive first-pass metabolism). IM: 100% for immediate-release. Long-acting IM: fraction absorbed over depot injection. |
| Onset of Action | Oral: 1-2 hours (peak plasma concentration). Clinical antipsychotic effect: 1-2 weeks for initial response, full effect 4-6 weeks. IM: 30-60 minutes for peak levels. |
| Duration of Action | Oral: 24 hours (maintained with once or twice daily dosing). IM depot: 2 weeks between doses. Clinical effect duration depends on receptor occupancy. |
| Action Class | Atypical Antipsychotics |
| Brand Substitutes | Sycodone 2mg Tablet, Relivon 2mg Tablet, Restonorm 2mg Tablet, Genrest 2mg Tablet, Zisdon 2mg Tablet, Sycodone 1mg Tablet, Rion 1mg Tablet, Zepid 1mg Tablet, Rozidal 1mg Tablet, Regrace 1mg Tablet, Ristab 4mg Tablet, Rion 4mg Tablet, Rozidal 4mg Tablet, Sizomax 4mg Tablet, Respik Plus 4mg Tablet, Riszes 3mg Tablet, Rpn 3mg Tablet, Ridone 3mg Tablet, Rispee 3mg Tablet, Eritric 3mg Tablet |
2-8 mg orally once daily or divided twice daily; maximum 16 mg/day
| Dosage form | TABLET |
| Renal impairment | CrCl <30 mL/min: initial 0.5 mg twice daily, increase by 0.5 mg increments; max 3 mg/day |
| Liver impairment | Child-Pugh class A or B: initial 0.5 mg twice daily, increase by 0.5 mg increments; max 3 mg/day; Child-Pugh C: not studied |
| Pediatric use | 13-17 yr: 0.5 mg once daily, titrate by 0.5-1 mg/day at ≥24 hr intervals; target 3 mg/day; max 6 mg/day. 10-12 yr: 0.5 mg once daily, titrate by 0.5 mg/day; target 1-2.5 mg/day; max 3 mg/day |
| Geriatric use | Initial 0.5 mg twice daily; increase by 0.5 mg increments; max 3 mg/day; 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 RISPERDAL (RISPERDAL).
| Breastfeeding | Risperidone and its active metabolite 9-hydroxyrisperidone are excreted in breast milk. Milk-to-plasma ratio (M/P) approximately 0.42-0.44. Relative infant dose is about 4-9% of maternal weight-adjusted dose. Monitor infant for sedation, poor feeding, and extrapyramidal symptoms. Consider benefits of breastfeeding vs. risk. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: Risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates if exposed during third trimester. Overall, not considered a major teratogen. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperidone 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 (e.g., stroke, transient ischemic attack) in elderly with dementia","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Hyperglycemia and diabetes mellitus","Weight gain","Dyslipidemia","Orthostatic hypotension and syncope","Seizures","Leukopenia, neutropenia, and agranulocytosis","QT interval prolongation","Hyperprolactinemia","Body temperature dysregulation","Dysphagia","Priapism","Thrombotic thrombocytopenic purpura (TTP)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, glucose levels, weight, and psychiatric status. For fetus/neonate, monitor for extrapyramidal symptoms, sedation, and withdrawal signs after delivery. Consider ultrasound for fetal growth if prolonged use. |
| Fertility Effects | Risperidone may increase serum prolactin levels, potentially causing menstrual irregularities, anovulation, and reduced fertility. Effects are reversible upon dose reduction or discontinuation. |