LURASIDONE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Lurasidone is an atypical antipsychotic that acts as a full antagonist at D2 and 5-HT2A receptors, with high affinity for 5-HT7 and 5-HT1A receptors, moderate affinity for alpha2C and alpha2A adrenergic receptors, and no appreciable affinity for H1, M1, or alpha1 receptors.
| Metabolism | Primarily metabolized by CYP3A4; also undergoes metabolism via carbonyl reduction and N-dealkylation. Major metabolites: ID-14283 (active), ID-14326, and ID-11614. |
| Excretion | Approximately 80% of total radioactivity recovered in feces (67% as metabolites, 9% as unchanged drug) and 19% in urine (mostly metabolites); less than 1% excreted as unchanged parent in urine. |
| Half-life | Terminal elimination half-life is approximately 18 hours (range 14–24 hours), supporting once-daily dosing. |
| Protein binding | 99% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 6173 L (or ~88 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 9–19% (mean ~12%) when taken with food (≥350 calories); absorption is increased 2–3 fold with food. |
| Onset of Action | Oral: Onset of clinical effect (antipsychotic) may be observed within 1–2 weeks, with full effect over 4–6 weeks. |
| Duration of Action | Duration of clinical effect persists for approximately 24 hours due to once-daily administration; steady state achieved after 6–7 days. |
| Molecular Weight | 492.9 |
40 mg orally once daily initially, titrated to 80 mg once daily; maximum 80 mg per day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate impairment (CrCl ≥ 30 mL/min); not recommended for severe impairment (CrCl < 30 mL/min) due to lack of data. |
| Liver impairment | Mild impairment (Child-Pugh A): no adjustment. Moderate impairment (Child-Pugh B): reduce dose: initial 20 mg daily, max 80 mg daily. Severe impairment (Child-Pugh C): not recommended (no data). |
| Pediatric use | Not FDA-approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at lower dose (40 mg once daily); titrate slowly with monitoring for orthostatic hypotension, sedation, and QT prolongation. |
| 1st trimester | There is no adequate and well-controlled study in pregnant women; use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | Same as T1; may increase risk of extrapyramidal symptoms and/or withdrawal symptoms in neonates. |
| 3rd trimester | Neonates exposed during third trimester are at risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tremor). |
Clinical note
Strong CYP3A4 inhibitors and inducers are contraindicated Can cause somnolence and akathisia.
| Placental transfer | Lurasidone crosses the placenta in animal studies; unknown degree in humans. |
| Breastfeeding | Not recommended during breastfeeding; it is excreted in milk in animal studies; consider alternative agents. |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lurasidone is not approved for the treatment of patients with dementia-related psychosis.
| Common Effects | Nausea Vomiting Weight gain Sleepiness Dryness in mouth Indigestion Parkinsonism Akathisia inability to stay still Anxiety Stomach discomfort Restlessness Upper abdominal pain Agitation Insomnia difficulty in sleeping Increased saliva production |
| Serious Effects |
Known hypersensitivity to lurasidone or any component of the formulationConcomitant use with strong CYP3A4 inducers (e.g., rifampin, St. John's wort)
| Precautions | Increased mortality in elderly patients with dementia-related psychosis, Suicidal thoughts and behaviors, Cerebrovascular adverse events (e.g., stroke) in elderly dementia patients, Neuroleptic malignant syndrome (NMS), Tardive dyskinesia, Metabolic changes (hyperglycemia, dyslipidemia, weight gain), Hyperprolactinemia, Leukopenia, neutropenia, and agranulocytosis, Orthostatic hypotension and syncope, Seizures, Body temperature dysregulation, Dysphagia, Cognitive and motor impairment |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | Limited human data; animal studies show fetal harm at doses ≥ human therapeutic range. First trimester: potential risk of congenital malformations (neural tube defects, cardiac anomalies) based on animal studies. Second/third trimester: risk of neonatal extrapyramidal symptoms, withdrawal, or poor neonatal adaptation syndrome following late third trimester exposure. |
| Fetal Monitoring | Monitor for fetal growth, amniotic fluid volume, and fetal movement. Assess neonatal adaptation post-delivery (e.g., respiratory depression, feeding difficulties, tremors). Maternal monitoring: weight, metabolic parameters (glucose, lipids), EPS, and QTc interval. |
| Fertility Effects | In animal studies, no impairment of male or female fertility at doses up to 2-4 times MRHD. In humans, hyperprolactinemia may occur (due to D2 blockade) leading to menstrual irregularities, galactorrhea, or reduced libido, potentially impairing fertility. |
| Food/Dietary | Take with food (≥350 calories). Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition increasing lurasidone exposure. High-fat meal may further increase absorption. |
| Clinical Pearls | Lurasidone requires administration with food (≥350 calories) to enhance absorption by ~2-fold; avoid grapefruit/grapefruit juice. Monitor for akathisia, somnolence, and metabolic changes (minimal weight gain relative to other atypicals). Use with caution in renal impairment (CrCl ≤30 mL/min: max dose 40 mg/day) and hepatic impairment (Child-Pugh moderate: max 40 mg/day; severe: not recommended). QT prolongation risk, especially in hypokalemia or concurrent QT-prolonging drugs. Efficacy in bipolar depression with unique receptor profile (5-HT7 antagonism). |
| Patient Advice | Take lurasidone with food (at least 350 calories) to ensure proper absorption. · Avoid grapefruit and grapefruit juice while taking this medication. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. · Report any involuntary muscle movements, restlessness, or changes in mood immediately. · Limit alcohol consumption as it may increase side effects like drowsiness. |