LATUDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LATUDA (LATUDA).
Lurasidone is an atypical antipsychotic with high affinity for dopamine D2, serotonin 5-HT2A, and serotonin 5-HT7 receptors, and moderate affinity for serotonin 5-HT1A receptors. It acts as an antagonist at D2 and 5-HT2A receptors, and as a partial agonist at 5-HT1A receptors. The exact mechanism of action in schizophrenia and bipolar depression is unknown but is thought to involve modulation of these receptors.
| Metabolism | Primarily metabolized via CYP3A4. Minor contributions from CYP2D6 and other pathways. |
| Excretion | Approximately 80% of the dose is eliminated in feces (mostly as unchanged drug and metabolites) and about 10% in urine. Less than 2% is excreted as unchanged lurasidone in urine. |
| Half-life | Terminal elimination half-life is approximately 20–40 hours (mean about 29 hours) in adults, supporting once-daily dosing. Steady-state is reached within 7 days. |
| Protein binding | Lurasidone is highly protein-bound (approximately 99%) primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 6.2 L/kg (or 400–600 L), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 9–19% (mean ~12–15%) when administered with food (at least 350 calories). Administration with food increases Cmax and AUC by about 2-fold compared to fasting. |
| Onset of Action | Not fully characterized; antipsychotic effects may be observed within 1–2 weeks of oral administration, but full therapeutic response may require up to 4–6 weeks. |
| Duration of Action | Dosing interval is once daily due to its half-life. Steady-state concentrations are maintained with once-daily administration, providing sustained receptor occupancy over 24 hours. |
40 mg orally once daily initially, titrated to 80-160 mg once daily; maximum 160 mg/day. Administer with food (at least 350 calories).
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 20 mg daily initially, max 80 mg/day. GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: 20 mg daily initially, max 80 mg/day. Child-Pugh Class C: contraindicated. |
| Pediatric use | Age 13-17 years: initiate at 40 mg daily, titrate to 80-120 mg daily. Safety and efficacy for <13 years not established. |
| Geriatric use | Initiate at 20 mg daily, max 80 mg daily. Caution due to increased sensitivity (orthostatic hypotension, sedation). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LATUDA (LATUDA).
| Breastfeeding | It is not known whether lurasidone is excreted in human breast milk. Limited data suggest minimal excretion; the M/P ratio is unknown. Caution is advised due to potential for adverse effects in the infant. Consider benefits of breastfeeding and importance of drug to mother. |
| Teratogenic Risk | Lurasidone (LATUDA) is classified as Pregnancy Category B. Human data are limited; animal studies have not demonstrated teratogenicity at doses up to 15 times the maximum recommended human dose. However, neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal symptoms and/or withdrawal symptoms after delivery. Use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. LATUDA is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort)","Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir)","Known hypersensitivity to lurasidone or any component of the formulation"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Suicidal thoughts and behaviors","Cerebrovascular adverse events (including stroke) in elderly patients with dementia","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Metabolic changes (hyperglycemia, diabetes mellitus, dyslipidemia, weight gain)","Hyperprolactinemia","Leukopenia, neutropenia, and agranulocytosis","Orthostatic hypotension and syncope","Seizures","Potential for cognitive and motor impairment","Body temperature regulation disruption","Dysphagia","Priapism","Activation of mania/hypomania"] |
Loading safety data…
| Fetal Monitoring | Monitor for maternal adverse effects (e.g., somnolence, akathisia, metabolic changes). In neonates, monitor for extrapyramidal signs, feeding difficulties, sedation, and respiratory distress. Consider fetal growth monitoring if prolonged use during pregnancy. |
| Fertility Effects | In animal studies, lurasidone did not impair fertility at doses up to 2 times the maximum recommended human dose on a mg/m² basis. Effects on human fertility are unknown. |