WARNINGS AND PRECAUTIONS ----------------

1 HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------- WARNINGS AND PRECAUTIONS ---------------------------------- These highlights do not include all the information needed to use CAPLYTA safely Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: and effectively. See full prescribing information for CAPLYTA. Increased incidence of cerebrovascular adverse reactions ( , stroke and transient CAPLYTA (lumateperone) capsules, for oral use ischemic attack). ( ). Initial Approval: 2019 Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( ). WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH Tardive Dyskinesia: Discontinue treatment if clinically appropriate.

2 ( ). DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and See full prescribing information for complete boxed warning. weight gain. ( ). Elderly patients with dementia-related psychosis treated with antipsychotic drugs Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC). are at an increased risk of death. CAPLYTA is not approved for the treatment of in patients with pre-existing low white blood cell count (WBC) or history of leukopenia patients with dementia-related psychosis. ( ) or neutropenia. Consider discontinuing CAPLYTA if clinically significant decline in WBC.

3 Antidepressants increased the risk of suicidal thoughts and behaviors in occurs in absence of other causative factors. ( ). pediatric and young adult patients. Closely monitor all antidepressant-treated Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients for worsening and emergence of suicidal thoughts and behaviors. Safety patients with known cardiovascular or cerebrovascular disease, and risk of dehydration and effectiveness of CAPLYTA have not been established in pediatric patients. or syncope. ( ). ( , ) Seizures: Use cautiously in patients with a history of seizure or with conditions that lower seizure threshold. ( ). Potential for Cognitive and Motor Impairment: Use caution when operating machinery.

4 ------------------------------------ RECENT MAJOR CHANGES ------------------------------------ ( ). Boxed Warning 12/2021. Indication and Usage (1) 12/2021 --------------------------------------- ADVERSE REACTIONS --------------------------------------- Dosage and Administration ( ) 12/2021 Most common adverse reactions in clinical trials (incidence > 5% and greater than twice WARNINGS and PRECAUTIONS ( , , , ) 12/2021 placebo) were ( ): Schizophrenia: somnolence/sedation and dry mouth ------------------------------------ INDICATIONS AND USAGE ------------------------------------- Bipolar depression: somnolence/sedation, dizziness, nausea, dry mouth. CAPLYTA is an atypical antipsychotic indicated for the treatment of: To report SUSPECTED ADVERSE REACTIONS, contact Intra-Cellular Therapies, Inc.

5 At Schizophrenia in adults. (1) 1-888-611-4824 or FDA at 1-800-FDA-1088 or Depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate. (1) --------------------------------------- DRUG INTERACTIONS --------------------------------------- CYP3A4 inducers: Avoid concomitant use. ( , ). -------------------------------- DOSAGE AND ADMINISTRATION --------------------------------- Moderate or strong CYP3A4 inhibitors: Avoid concomitant use. ( , ). The recommended dosage of CAPLYTA is 42 mg once daily with or without food. ( ). Dose titration is not required. ( ) --------------------------------- USE IN SPECIFIC POPULATIONS --------------------------------- Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with ------------------------------ DOSAGE FORMS AND STRENGTHS -------------------------------- third trimester exposure.

6 ( ). Capsules: 42 mg (3) Lactation: Breastfeeding not recommended. ( ). -------------------------------------- CONTRAINDICATIONS ---------------------------------------- Moderate or severe hepatic impairment: Avoid use. ( , ). Known hypersensitivity to lumateperone or any components of CAPLYTA. (4) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Revised: 12/2021. FULL PRESCRIBING INFORMATION: CONTENTS* 6 ADVERSE REACTIONS. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED Clinical Trials Experience PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS 7 DRUG INTERACTIONS. 1 INDICATIONS AND USAGE Drugs Having Clinically Important Interactions with CAPLYTA.

7 2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS. Recommended Dosage Pregnancy Dosage Recommendations for Concomitant Use with CYP3A4 Inducers Lactation and Moderate or Strong CYP3A4 Inhibitors Females and Males of Reproductive Potential Dosage Recommendations for Patients with Hepatic Impairment Pediatric Use 3 DOSAGE FORMS AND STRENGTHS Geriatric Use 4 CONTRAINDICATIONS Hepatic Impairment 5 WARNINGS AND PRECAUTIONS 10 OVERDOSAGE. Increased Mortality in Elderly Patients with Dementia-Related Psychosis 11 DESCRIPTION. Suicidal Thoughts and Behaviors in Children, Adolescents and Young Adults 12 CLINICAL PHARMACOLOGY. Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Mechanism of Action Dementia-Related Psychosis Pharmacodynamics Neuroleptic Malignant Syndrome Pharmacokinetics Tardive Dyskinesia 13 NONCLINICAL TOXICOLOGY.

8 Metabolic Changes Carcinogenesis, Mutagenesis, Impairment of Fertility Leukopenia, Neutropenia, and Agranulocytosis Animal Toxicology and/or Pharmacology Orthostatic Hypotension and Syncope 14 CLINICAL STUDIES. Falls Schizophrenia Seizures Depressive Episodes Associated with Bipolar I or II Disorder Potential for Cognitive and Motor Impairment 16 HOW SUPPLIED/ STORAGE AND HANDLING. Body Temperature Dysregulation 17 PATIENT COUNSELING INFORMATION. Dysphagia *Sections or subsections omitted from the Full Prescribing Information are not listed. FULL PRESCRIBING INFORMATION Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behavior in the Pooled Placebo- controlled Trials of Antidepressants in Pediatric* and WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH Adult Patients DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS.

9 Drug-Placebo Difference in Number of Patients of Increased Mortality in Elderly Patients with Dementia-Related Psychosis Age Range Suicidal Thoughts or Behaviors per 1000 Patients Treated 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 Increases Compared to Placebo patients with dementia-related psychosis [see WARNINGS and PRECAUTIONS ( )]. <18 years old 14 additional patients Suicidal Thoughts and Behaviors 18-24 years old 5 additional patients Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric Decreases Compared to Placebo and young adults in short-term studies.

10 Closely monitor all antidepressant- treated patients for clinical worsening, and for emergence of suicidal thoughts and 25-64 years old 1 fewer patient behaviors [see WARNINGS and PRECAUTIONS ( )]. The safety and effectiveness 65 years old 6 fewer patients of CAPLYTA have not been established in pediatric patients [see Use in Specific *CAPLYTA is not approved for use in pediatric patients. Populations ( )]. It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, 1 INDICATIONS AND USAGE and young adults extends to longer-term use, , beyond four months. However, there CAPLYTA is indicated for the treatment of: is substantial evidence from placebo- controlled maintenance trials in adults with MDD.