coadministered with moderate CYP3A4 inhibitors.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.rifabutinSerious - Use Alternative (1)rifabutin will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.rifampinSerious - Use Alternative (1)rifampin will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.rifapentineSerious - Use Alternative (1)rifapentine will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.ritonavirMonitor Closely (1)ritonavir will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.saquinavirMonitor Closely (1)saquinavir will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.schisandraMonitor Closely (1)schisandra will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.secobarbitalSerious - Use Alternative (1)secobarbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.sertralineMonitor Closely (1)sertraline will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.sotorasibSerious - Use Alternative (1)sotorasib will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.St John's WortSerious - Use Alternative (1)St John's Wort will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.telotristat ethylSerious - Use Alternative (1)telotristat ethyl will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.tetracyclineMonitor Closely (1)tetracycline will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.verapamilMonitor Closely (1)verapamil will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.voxelotorMonitor Closely (1)voxelotor will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors. >10% Schizophrenia Somnolence/sedation (24%) Bipolar disorder (adjunctive therapy) Somnolence/sedation (13%) Dizziness (11%) Bipolar disorder (monotherapy) Headache (14%) Somnolence/sedation (13%) 1-10% Schizophrenia 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%) Bipolar disorder (adjunctive therapy) Nausea (9%) Dry mouth (5%) Vomiting (4%) Extrapyramidal symptoms, adjunctive therapy (4%) Diarrhea (3%) Upper respiratory tract infection (3%) Blurred vision (3%) Increased blood prolactin (2%) Extrapyramidal symptoms, monotherapy (1.3%) Bipolar disorder (monotherapy) Dizziness (8%) Nausea (8%) Dry mouth (5%) Diarrhea (4%) Vomiting (4%) Abdominal pain (2%) Upper respiratory tract infection (2%) Frequency Not Defined Dystonia Postmarketing Reports Burning sensation, including skin burning sensation Black Box Warnings Increased mortality in elderly patients with dementia-related psychosis Increased mortality in elderly patients with dementia-related psychosis observed when treated with antipsychotic drugs Not approved for treatment of patients with dementia-related psychosis Suicidal thoughts and behaviors Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors Safety and effectiveness not established in pediatric patients Contraindications History of hypersensitivity; reactions have included pruritus, rash (eg, allergic dermatitis, papular rash, and generalized rash), and urticaria Cautions 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 Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during initial few months of drug therapy, and at times of dosage changes; counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider; consider changing therapeutic regimen, including possibly discontinuing therapy, in patients whose depression is persistently worse, or who are experiencing suicidal thoughts or behaviors 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 Drug interaction overview CYP3A4 inhibitors ​Strong inhibitors: Reduce lumateperone dose to 10.5 mg/day Moderate inhibitors: Reduce lumateperone dose to 21 mg/day Moderate or strong CYP3A4 inhibitors increase systemic exposure of lumateperone CYP3A4 inducers Avoid coadministration CYP3A4 inducers decrease systemic exposure of lumateperone 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 Lumateperone and its metabolites are present in human breast milk in low amounts; in a clinical lactation study, lumateperone was detected in human milk at an estimated daily infant dose 0.0004 mg/kg, with a relative infant dose (RID) of 0.06% the maternal weight-adjusted dosage Several major circulating metabolites were similarly detected in breast milk in low amounts; however, aniline metabolites were not present in milk or maternal plasma at quantifiable levels; there are no data on effects of therapy on breastfed infant or effects on milk production Consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. 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 Absorption Bioavailability: 4.4% Peak plasma time: 1-2 hr Ingestion with high-fat meal Lowers lumateperone mean peak plasma concentration by 33% and increases mean AUC by 9% Median peak plasma time delayed ~1 hr (from 1 hr at fasted state to 2 hr in the presence of food) Distribution Protein bound: 97.4% Vd: 4.1 L/kg Metabolism Extensively metabolized with >20 metabolites identified in vivo Multiple enzymes, including but not limited to uridine 5’-diphospho- glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2, are involved in the metabolism of lumateperone Elimination Half-life: ~18 hr (IV administration) Clearance: 27.9 L/hr Excretion: Feces: 29%; urine 58% Oral Administration Administer with food Storage Store at controlled room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. QL Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. ST Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. Plans Select State: Alabama Alaska Arizona Arkansas