CAPLYTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAPLYTA (CAPLYTA).
CAPLYTA (lumateperone) is a second-generation antipsychotic with a unique mechanism of action. It acts as a serotonin 5-HT2A receptor antagonist and a dopamine D2 receptor antagonist. It also functions as a serotonin transporter (SERT) inhibitor and has partial agonist activity at dopamine D1 receptors. Additionally, it modulates glutamate via effects on NMDA receptors and mTOR signaling.
| Metabolism | Primarily metabolized by CYP3A4 and, to a lesser extent, CYP2D6. The major metabolic pathways include oxidation and glucuronidation. |
| Excretion | Following oral administration of lumateperone, approximately 81% of the dose is excreted in feces (mostly as metabolites) and 12% in urine (as metabolites). Less than 1% is excreted unchanged in urine. |
| Half-life | The terminal elimination half-life of lumateperone is approximately 18 hours, supporting once-daily dosing with steady state achieved within 5 days. |
| Protein binding | Lumateperone is approximately 97.4% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The volume of distribution is approximately 7.9 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Absolute oral bioavailability is approximately 3% due to extensive first-pass metabolism. |
| Onset of Action | Clinical response may be observed within 1-2 weeks of daily oral dosing; however, full therapeutic effects may require up to 4-6 weeks. |
| Duration of Action | Once-daily dosing maintains therapeutic plasma concentrations over 24 hours, with sustained efficacy in schizophrenia and bipolar depression during continued administration. |
42 mg orally once daily, with or without food. Initiate at 42 mg/day; no dose titration required.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), pharmacokinetic data not available; use is not recommended. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). For moderate or severe hepatic impairment (Child-Pugh B or C), pharmacokinetic data not available; use is not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). No dosing guidelines available. |
| Geriatric use | No dose adjustment based on age alone; however, elderly patients may have reduced renal or hepatic function. Use caution with monitoring for adverse effects. In pharmacokinetic studies, no significant age-related differences observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CAPLYTA (CAPLYTA).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Caution advised due to potential for infant sedation, EPS, or growth effects. |
| Teratogenic Risk | Pregnancy Category C. First trimester: No adequate human studies; animal studies show fetal developmental toxicity at exposures similar to clinical doses. Second/third trimester: Neonates exposed late may exhibit extrapyramidal symptoms (EPS) and/or withdrawal after delivery. |
| Fetal Monitoring |
■ FDA Black Box Warning
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to lumateperone or any of the excipients in CAPLYTA"]
| Precautions | ["Increased mortality in elderly patients with dementia-related psychosis","Cerebrovascular adverse reactions, including stroke, in elderly patients with dementia-related psychosis","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","Metabolic changes: hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain","Leukopenia, neutropenia, and agranulocytosis","Orthostatic hypotension and syncope","Falls","Seizures","Potential for cognitive and motor impairment","Body temperature dysregulation","Dysphagia","Anticholinergic effects"] |
| Food/Dietary | Take with food to enhance absorption. Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and may increase lumateperone levels. No significant interactions with other foods. |
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| Monitor for maternal EPS, metabolic changes (glucose, lipids), and weight. Fetal monitoring for growth and movement. Neonatal monitoring for EPS, sedation, and withdrawal symptoms post-delivery. |
| Fertility Effects | In animal studies, no adverse effects on fertility observed. Human data insufficient; may cause hyperprolactinemia potentially impairing fertility. |
| Clinical Pearls | CAPLYTA (lumateperone) is an atypical antipsychotic approved for schizophrenia and bipolar depression. It has a unique mechanism: D2, 5-HT2A, and SERT antagonism with glutamate modulation. Key pearls: (1) No need for dose titration; start at 42 mg once daily with food. (2) CYP3A4 substrate; avoid strong CYP3A4 inhibitors (e.g., ketoconazole) or reduce dose to 21 mg. (3) May cause somnolence/sedation; caution with driving. (4) Low risk of metabolic side effects (weight gain, dyslipidemia) compared to other atypicals. (5) No QTc prolongation at clinically relevant doses. (6) Can be used in renal or hepatic impairment without dose adjustment (except severe hepatic: 21 mg). (7) Not approved for dementia-related psychosis. |
| Patient Advice | Take CAPLYTA exactly as prescribed, once daily with food. Swallow capsules whole; do not crush or chew. · Do not stop taking this medication suddenly without talking to your doctor; it may cause withdrawal symptoms. · Avoid alcohol and grapefruit juice while taking CAPLYTA, as they may increase side effects or alter drug levels. · This drug may cause drowsiness or dizziness; do not drive or operate heavy machinery until you know how it affects you. · Report any unusual muscle movements, restlessness, or fever with stiff muscles to your doctor immediately. · Contact your doctor if you experience thoughts of suicide or worsening depression, especially in the first few weeks of treatment. · Store at room temperature away from moisture and heat. · Take missed doses as soon as you remember, but skip if it is almost time for your next dose. Do not double dose. |