Lumateperone

Indications

Lumateperone is used for: Schizophrenia

Adult Dose

Schizophrenia Indicated for treatment of schizophrenia 42 mg PO qDay Dose titration not required Hepatic impairment Mild (Child-Pugh A): No dose adjustment required Moderate or severe (Child-Pugh B or C): Avoid use; increased systemic exposure to lumateperone associated

Child Dose

Renal Dose

Renal impairment: No dose adjustment required

Administration

Contra Indications

History of hypersensitivity; reactions have included pruritus, rash (eg, allergic dermatitis, papular rash, and generalized rash), and urticaria

Precautions

Neuroleptic malignant syndrome (NMS), a potentially fatal symptom complex, reported with administration of antipsychotic drugs; if NMS suspected, immediately discontinue lumateperone and provide intensive symptomatic treatment and monitoring Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs; risk appears to be highest among elderly individuals, especially women, but it is not possible to predict which patients are likely to develop the syndrome May cause metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain Leukopenia and neutropenia reported with antipsychotic agents, including lumateperone; agranulocytosis reported with other agents in the class May cause orthostatic hypotension and syncope; risk is greatest during initial dose administration Antipsychotics, including lumateperone, may cause somnolence, postural hypotension, and motor and sensory instability, which may lead to falls and, consequently, fractures and other injuries May cause seizures; risk is greatest with history of seizures or with conditions that lower seizure threshold May cause somnolence and has the potential to impair judgment, thinking, and motor skills May disrupt the body’s ability to reduce core body temperature; strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevated core body temperature Esophageal dysmotility and aspiration reported with antipsychotic drug use Geriatric patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death Geriatric patients with dementia who were treated with antipsychotics had a higher incidence of stroke and transient ischemic attacks, including fatal stroke

Pregnancy-Lactation

Pregnancy Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery Available data from case reports on use in pregnant women are insufficient to establish any drug-associated risks for birth defects, miscarriage, or adverse maternal or fetal outcomes Register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ Animal studies No malformations were observed with oral administration of lumateperone to pregnant rats and rabbits during organogenesis at doses up to 2.4 and 9.7 times, respectively, the maximum recommended human dose (MRHD) of 42 mg/day on a mg/m2 basis When pregnant rats were administered lumateperone during organogenesis through lactation, the number of perinatal deaths of pups was increased at 4.9 times the MRHD, with no adverse effects on pups at 2.4 times the MRHD Clinical considerations There is risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth; unknown if this is a direct result of the illness or other comorbid factors Infertility Based on findings from animal studies, lumateperone may impair male and female fertility Lactation Data are not available regarding presence of lumateperone or its metabolites in human milk, effect on breastfed infants, or effect on milk production

Interactions

Adverse Effects

Side effects of Lumateperone : >10% Somnolence/sedation (24%) 1-10% Nausea (9%) Extrapyramidal symptoms (6.7%) Dry mouth (6%) Dizziness (5%) Creatine phosphokinase increased (4%) Fatigue (3%) Vomiting (3%) Hepatic transaminases increased (2%) Decreased appetite (2%) Frequency Not Defined Dystonia

Mechanism of Action

The mechanism of action of lumateperone in the treatment of schizophrenia is unknown; however, efficacy could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors