INVEGA SUSTENNA® INVEGA SUSTENNA® (paliperidone palmitate) extended-release injectable suspension, for intramuscular use (paliperidone palmitate) extended-release injectable suspension, for intramuscular use --------------------------- DOSAGE FORMS AND STRENGTHS --------------------------- HIGHLIGHTS OF PRESCRIBING INFORMATION Extended-release injectable suspension: 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, These highlights do not include all the information needed to use 156 mg/mL, or 234 mg/1.5 mL (3) INVEGA SUSTENNA® safely and effectively. See full prescribing information for INVEGA SUSTENNA®. ----------------------------------- CONTRAINDICATIONS ----------------------------------- INVEGA SUSTENNA® (paliperidone palmitate) extended-release injectable Known hypersensitivity to paliperidone, risperidone, or to any excipients in suspension, for intramuscular use INVEGA SUSTENNA®. (4) Initial U.S. Approval: 2006 -----------------------------WARNINGS AND PRECAUTIONS ----------------------------- WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS • Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with WITH DEMENTIA-RELATED PSYCHOSIS Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse See full prescribing information for complete boxed warning. reactions (e.g. stroke, transient ischemic attack). (5.2) • Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of Elderly patients with dementia-related psychosis treated with antipsychotic drug and close monitoring. (5.3) drugs are at an increased risk of death. INVEGA SUSTENNA® is not approved for use in patients with dementia-related psychosis. (5.1) • QT Prolongation: Avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval. (5.4) • Tardive Dyskinesia: Discontinue drug if clinically appropriate. (5.5) -------------------------------- RECENT MAJOR CHANGES -------------------------------- • Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia Warning and Precautions (5.3, 5.5) 2/2021 and weight gain. (5.6) • Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure -------------------------------- INDICATIONS AND USAGE -------------------------------- and warn patients with known cardiovascular or cerebrovascular disease, and INVEGA SUSTENNA® is an atypical antipsychotic indicated for risk of dehydration or syncope. (5.7) • Treatment of schizophrenia in adults. (1) • Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts • Treatment of schizoaffective disorder in adults as monotherapy and as an (CBC) in patients with pre-existing low white blood cell count (WBC) or history adjunct to mood stabilizers or antidepressants. (1) of leukopenia or neutropenia. Consider discontinuing INVEGA SUSTENNA® if clinically significant decline in WBC in the absence of other causative factors. (5.9) -----------------------------DOSAGE AND ADMINISTRATION----------------------------- • Hyperprolactinemia: Prolactin elevations occur and persist during chronic • For intramuscular injection only. (2.1) administration. (5.10) • Each injection must be administered only by a healthcare professional. (2.1) • Potential for Cognitive and Motor Impairment: Use caution when operating • For deltoid injection, use 1-inch 23G needle for patients weighing less than 90 kg machinery. (5.11) or 1 ½-inch 22G needle for patients weighing 90 kg or more. For gluteal injection, • Seizures: Use cautiously in patients with a history of seizures or with conditions use 1 ½-inch 22G needle regardless of patient weight. (2.1) that lower the seizure threshold. (5.12) Initiation Dosing Monthly Maximum ----------------------------------- ADVERSE REACTIONS ----------------------------------- a Indication (deltoid) Maintenance Dose Monthly Dose The most common adverse reactions (incidence ≥ 5% and occurring at least twice Day 1 Day 8 (deltoid or gluteal) as often as placebo) were injection site reactions, somnolence/sedation, dizziness, Schizophrenia (2.2) 234 mg 156 mg 39-234 mgb 234 mg akathisia, and extrapyramidal disorder. (6) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Schizoaffective 234 mg 156 mg 78-234 mgc 234 mg Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or disorder (2.2) www.fda.gov/medwatch a Administered 5 weeks after the first injection. b The recommended maintenance dose for treatment of schizophrenia is 117 mg. ----------------------------------- DRUG INTERACTIONS ----------------------------------- Some patients may benefit from lower or higher maintenance doses within the • Drugs that may cause orthostatic hypotension: An additive effect may occur additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). when co-administered with INVEGA SUSTENNA®. (7.1) c Adjust dose based on tolerability and/or efficacy using available strengths. The • Strong CYP3A4/P-glycoprotein (P-gp) inducers: Avoid using a strong inducer of 39 mg strength was not studied in the long-term schizoaffective disorder study. CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John’s Wort) during a ® • For patients naïve to oral paliperidone or oral or injectable risperidone, establish dosing interval for INVEGA SUSTENNA . If administering a strong inducer is tolerability with oral paliperidone or oral risperidone prior to initiating treatment necessary, consider managing the patient using paliperidone extended release with INVEGA SUSTENNA®. (2.2) tablets. (2.5, 7.1, 12.3) • Missed Doses: To manage either a missed second initiation dose or a missed ----------------------------- USE IN SPECIFIC POPULATIONS ----------------------------- monthly maintenance dose, refer to the Full Prescribing Information. (2.3) Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates • Moderate to severe renal impairment (creatinine clearance < 50 mL/min): with third trimester exposure. (8.1) INVEGA SUSTENNA® is not recommended. (2.5) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient • Mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min): labeling. Administer 156 mg on treatment day 1 and 117 mg one week later, both administered in the deltoid muscle. Follow with monthly injections of 78 mg in Revised: 08/2021 either the deltoid or gluteal muscle. (2.5) 1 INVEGA SUSTENNA® (paliperidone palmitate) INVEGA SUSTENNA® (paliperidone palmitate) extended-release injectable suspension, for intramuscular use extended-release injectable suspension, for intramuscular use FULL PRESCRIBING INFORMATION: CONTENTS* 7 DRUG INTERACTIONS WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA- 7.1 Drugs Having Clinically Important Interactions with RELATED PSYCHOSIS INVEGA SUSTENNA® 1 INDICATIONS AND USAGE 7.2 Drugs Having No Clinically Important Interactions with ® 2 DOSAGE AND ADMINISTRATION INVEGA SUSTENNA 2.1 Administration Instructions 8 USE IN SPECIFIC POPULATIONS 2.2 Schizophrenia and Schizoaffective Disorder 8.1 Pregnancy 2.3 Missed Doses 8.2 Lactation 2.4 Use with Risperidone or with Oral Paliperidone 8.3 Females and Males of Reproductive Potential 2.5 Dosage Adjustments 8.4 Pediatric Use 2.6 Switching from Other Antipsychotics 8.5 Geriatric Use 2.7 Instructions for Use 8.6 Renal Impairment 3 DOSAGE FORMS AND STRENGTHS 8.7 Hepatic Impairment 8.8 Patients with Parkinson’s Disease or Lewy Body Dementia 4 CONTRAINDICATIONS 9 DRUG ABUSE AND DEPENDENCE 5 WARNINGS AND PRECAUTIONS 9.1 Controlled Substance 5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis 9.2 Abuse 5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly 9.3 Dependence Patients with Dementia-Related Psychosis 10 OVERDOSAGE 5.3 Neuroleptic Malignant Syndrome 10.1 Human Experience 5.4 QT Prolongation 10.2 Management of Overdosage 5.5 Tardive Dyskinesia 11 DESCRIPTION 5.6 Metabolic Changes 12 CLINICAL PHARMACOLOGY 5.7 Orthostatic Hypotension and Syncope 12.1 Mechanism of Action 5.8 Falls 12.2 Pharmacodynamics 5.9 Leukopenia, Neutropenia, and Agranulocytosis 12.3 Pharmacokinetics 5.10 Hyperprolactinemia 13 NONCLINICAL TOXICOLOGY 5.11 Potential for Cognitive and Motor Impairment 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.12 Seizures 13.2 Animal Toxicology and/or Pharmacology 5.13 Dysphagia 14 CLINICAL STUDIES 5.14 Priapism 14.1 Schizophrenia 5.15 Disruption of Body Temperature Regulation 14.2 Schizoaffective Disorder 6 ADVERSE REACTIONS 16 HOW SUPPLIED/STORAGE AND HANDLING 6.1 Clinical Trials Experience 17 PATIENT COUNSELING INFORMATION 6.2 Postmarketing Experience *Sections or subsections omitted from the full prescribing information are not listed. FULL PRESCRIBING INFORMATION 2.2 Schizophrenia and Schizoaffective Disorder For patients who have never taken oral paliperidone or oral or injectable WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS risperidone, it is recommended to establish tolerability with oral paliperidone or WITH DEMENTIA-RELATED PSYCHOSIS oral risperidone prior to initiating treatment with INVEGA SUSTENNA®. Elderly patients with dementia-related psychosis treated with antipsychotic The recommended dosing of INVEGA SUSTENNA® for each approved indication is drugs are at an increased risk of death. INVEGA SUSTENNA® is not approved displayed in Table 1. The recommended initiation of INVEGA SUSTENNA® is with a for use in patients with dementia-related psychosis. [see Warnings and dose of 234 mg on treatment day 1 and 156 mg one week later, both administered Precautions