RISPERIDONE
Clinical safety rating: safe
Animal studies have demonstrated safety
Risperidone is an atypical antipsychotic that antagonizes dopamine D2 receptors and serotonin 5-HT2A receptors. It also has moderate affinity for alpha1-adrenergic and H1-histaminergic receptors, and low affinity for muscarinic receptors.
| Metabolism | Extensively metabolized in the liver via CYP2D6 and CYP3A4 to 9-hydroxyrisperidone (paliperidone), which has similar pharmacological activity. The parent drug and metabolite are equally active. |
| Excretion | Renal (70% as metabolites, 14% as parent drug) and fecal (14%) |
| Half-life | Risperidone: 3 hours (CYP2D6 extensive metabolizers), 20 hours (poor metabolizers); active metabolite 9-hydroxyrisperidone: 21-30 hours; steady-state reached in 5-6 days |
| Protein binding | Risperidone: 90% bound to albumin and alpha-1-acid glycoprotein; 9-hydroxyrisperidone: 77% bound |
| Volume of Distribution | Risperidone: 1-2 L/kg; 9-hydroxyrisperidone: 0.5-1 L/kg; extensive tissue distribution |
| Bioavailability | Oral: 70% (tablet), 70% (oral solution); intramuscular: 100% for immediate-release, 28% for long-acting injection relative to oral |
| Onset of Action | Oral: 1-2 hours for antipsychotic effect, up to 1-2 weeks for full therapeutic response; intramuscular: 15-30 minutes for sedation, 1-2 weeks for antipsychotic effect |
| Duration of Action | Oral: 24 hours with once-daily dosing; intramuscular: 2 weeks for the long-acting formulation (Risperdal Consta) after steady state achieved |
Initial 2 mg orally once daily, titrated to target dose of 4-6 mg orally once daily (or divided twice daily); maximum 16 mg/day. Alternatively, long-acting IM injection: 25 mg IM every 2 weeks.
| Dosage form | SOLUTION |
| Renal impairment | CrCl ≥30 mL/min: no adjustment. CrCl <30 mL/min: initiate at 0.5 mg orally twice daily for at least 1 week, then increase by 0.5 mg twice daily as tolerated; maximum 3 mg/day. |
| Liver impairment | Child-Pugh Class A or B: initiate at 0.5 mg orally twice daily, increase cautiously. Class C: avoid or use with extreme caution; no specific established dose. |
| Pediatric use | Adolescents (13-17 yr) with schizophrenia: initial 0.5 mg orally once daily, titrate to 3 mg/day as tolerated. Children (10-17 yr) with bipolar mania: initial 0.5 mg once daily, titrate to 1-2.5 mg/day. Weight-based not standard; use fixed dosing. |
| Geriatric use | Initiate at 0.5 mg orally once daily; increase by 0.5 mg/day increments; target dose 1-2 mg/day; monitor for orthostasis and extrapyramidal symptoms. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP2D6 inhibitors may increase levels Can cause hyperprolactinemia and metabolic changes.
| Breastfeeding | Risperidone is excreted into breast milk with a milk-to-plasma (M/P) ratio of approximately 0.5 for the parent drug and 0.3 for the active moiety (risperidone + 9-hydroxyrisperidone). Relative infant dose (RID) is about 2-4% of the maternal weight-adjusted dose. Monitor the infant for sedation, poor feeding, and extrapyramidal effects. The benefit of breastfeeding should be weighed against potential risks. |
| Teratogenic Risk | Risperidone is not a major teratogen in humans based on available studies, but there is a slight increase in risk for gestational diabetes and preterm birth. Third-trimester exposure may cause neonatal extrapyramidal symptoms (e.g., agitation, hypertonia, tremors) and withdrawal symptoms (e.g., respiratory distress, feeding difficulties). |
■ 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.
| Common Effects | bipolar disorder |
| Serious Effects |
["Hypersensitivity to risperidone or any component of the formulation"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Cerebrovascular adverse events (stroke, TIA) in elderly with dementia","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Hyperglycemia and diabetes mellitus","Weight gain","Hyperprolactinemia","Orthostatic hypotension","Seizures","Leukopenia/neutropenia/agranulocytosis","QT interval prolongation","Priapism","Dysphagia","Body temperature dysregulation","Potential for cognitive and motor impairment"] |
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| Fetal Monitoring | For pregnant women: monitor for gestational diabetes, excessive weight gain, and signs of preeclampsia. For neonates: monitor for extrapyramidal symptoms (e.g., dystonia, rigidity), withdrawal, and respiratory depression. Consider therapeutic drug monitoring (TDM) during pregnancy as levels may decrease. |
| Fertility Effects | Risperidone can increase prolactin levels, leading to menstrual irregularities, galactorrhea, and possible ovulatory dysfunction in females, potentially reducing fertility. In males, hyperprolactinemia may cause decreased libido and erectile dysfunction. Effects are reversible upon dose reduction or discontinuation. |