`
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
`
` These highlights do not include all the information needed to use
`
`
`
`
`
`
`
` INVEGA SUSTENNA® safely and effectively. See full prescribing
`
`
`
`
`
`
`
` information for INVEGA SUSTENNA®.
`
`
`
`
`
`
`
` Mild renal impairment (creatinine clearance 50 mL/min to < 80 mL/min):
`
`
`
`
`
`
`
`
`
`
`
`
`
` 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 either the deltoid or gluteal muscle. (2.5)
`
`
`
`
`
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® (paliperidone palmitate) extended-release
`
`
`
` injectable suspension, for intramuscular use
`
`
`
`
` Initial U.S. Approval: 2006
`
`
`
`
`
`
`
`
`
`
` WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
`
`
`
`
`
` WITH DEMENTIA-RELATED PSYCHOSIS
`
`
` See full prescribing information for complete boxed warning.
`
`
`
`
`
`
`
`
` Elderly patients with dementia-related psychosis treated with
`
`
`
`
`
` antipsychotic drugs are at an increased risk of death. (5.1)
`
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® is not approved for use in patients with
`
`
`
`
`
`
`
` dementia-related psychosis. (5.1)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` ----------------------------RECENT MAJOR CHANGES-------------------------
`
`
`
`
`
`
`
` Dosage and Administration (2.5)
` 06/2017
` Warnings and Precautions (5.5)
`
`
`
`
` 12/2017
`
`
`
` Warnings and Precautions (5.8)
`
`
`
`
`
` 02/2017
`
` Warnings and Precautions (5.10)
`
`
`
`
` 06/2017
`
`
`
` ----------------------------INDICATIONS AND USAGE---------------------------
` INVEGA SUSTENNA® is an atypical antipsychotic indicated for
`
`
`
`
`
`
`
` Treatment of schizophrenia in adults. (1)
`
`
`
`
`
`
`
` Treatment of schizoaffective disorder in adults as monotherapy and as an
`
`
`
`
`
`
`
`
`
`
`
`
` adjunct to mood stabilizers or antidepressants. (1)
`
`
`
`
`
`
`
`
`
`
`
` -----------------------DOSAGE AND ADMINISTRATION----------------------
`
` For intramuscular injection only. (2.1)
`
`
`
`
`
`
`
` Each injection must be administered only by a health care professional.
`
`
`
`
`
`
`
`
`
`
`
`
`
` (2.1)
` For deltoid injection, use 1-inch 23G needle for patients weighing less than
`
`
`
`
`
`
`
`
`
`
`
` 90 kg or 1½-inch 22G needle for patients weighing 90 kg or more. For
`
`
`
`
`
`
`
`
`
`
`
`
`
` gluteal injection, use 1½-inch 22G needle regardless of patient weight.
`
`
`
`
`
`
`
`
`
`
` (2.1)
`
`
`
`
` Monthly
`
`
`
` Maintenance Dosea
`
`
`
` Maximum
`
`
`
` Monthly
`
`
`
` --------------------DOSAGE FORMS AND STRENGTHS---------------------
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Extended-release injectable suspension: 39 mg, 78 mg, 117 mg, 156 mg, or
`
`
`
`
` 234 mg (3)
`
`-------------------------------CONTRAINDICATIONS------------------------------
`
`
`
`
`
`
`
`
`
`
` Known hypersensitivity to paliperidone, risperidone, or to any excipients in
` INVEGA SUSTENNA®. (4)
`
`
`
`
` ---------------------------WARNINGS AND PRECAUTIONS-------------------
`
` Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients
`
`
`
`
`
`
`
`
`
` with Dementia-Related Psychosis: Increased incidence of cerebrovascular
`
`
`
`
`
`
`
` adverse reactions (e.g. stroke, transient ischemic attack). (5.2)
`
`
`
`
`
`
`
` Neuroleptic Malignant Syndrome: Manage with immediate discontinuation
`
`
`
`
`
`
`
`
`
` of drug and close monitoring. (5.3)
`
`
`
`
`
` 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)
`
`
`
`
`
`
`
`
`
` Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus,
`
`
`
`
`
`
` dyslipidemia and weight gain. (5.6)
`
`
`
`
`
` Orthostatic Hypotension and Syncope: Monitor heart rate and blood
`
`
`
`
`
`
`
`
`
`
` pressure and warn patients with known cardiovascular or cerebrovascular
`
`
`
`
`
`
`
`
` disease, and risk of dehydration or syncope. (5.7)
`
`
`
`
`
`
`
` Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood
`
`
`
`
`
`
`
` counts (CBC) in patients with pre-existing low white blood cell count
`
`
`
`
`
`
`
`
`
` (WBC) or history of leukopenia or neutropenia. Consider discontinuing
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® if clinically significant decline in WBC in the
`
`
`
`
`
`
`
`
`
`
` absence of other causative factors. (5.9)
`
`
`
`
`
` Hyperprolactinemia: Prolactin elevations occur and persist during chronic
`
`
`
`
`
`
`
`
`
` administration. (5.10)
`
` Potential for Cognitive and Motor Impairment: Use caution when
`
`
`
`
`
`
`
`
`
`
` operating machinery. (5.11)
`
`
` Seizures: Use cautiously in patients with a history of seizures or with
`
`
`
`
`
`
`
`
`
`
`
`
` conditions that lower the seizure threshold. (5.12)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Dose
`
`
`
` Initiation Dosing
`
`
`
`
`
`
`
` Indication
`
`
`
` (deltoid)
`
` Day 1
`
`
`
` Day 8
`
`
`
` (deltoid or gluteal)
`
`
`
`
`
`
`
`
`
`
`
` 234 mg
`
`
`
`
`
` 156 mg
`
`
`
`
`
` 234 mg
`
`
`
`
`
` 156 mg
`
`
`
` Schizophrenia
`
`
`
` (2.2)
`
`
`
` Schizoaffective
`
`
`
`
`
` disorder (2.2)
`
`
`
` 39-234 mgb
`
`
`
`
`
` 78-234 mgc
`
`
`
`
`
`
`
` 234 mg
`
`
`
`
`
` 234 mg
`
`a
`
`b
`
`
`c
`
`
`
`
`
`
`
`
` Administered 5 weeks after the first injection.
`
`
`
` The recommended maintenance dose for treatment of schizophrenia is 117
`
`
`
`
`
`
` mg. Some patients may benefit from lower or higher maintenance doses
`
`
`
`
`
`
`
` within the additional available strengths (39 mg, 78 mg, 156 mg, and 234
`
`
`
`
`
`
`
`
`
`
`
`
` mg).
`
`
`
`
`
`
`
`
`
` Adjust dose based on tolerability and/or efficacy using available strengths.
`
` The 39 mg strength was not studied in the long-term schizoaffective
`
`
`
`
`
`
`
`
`
` disorder study.
`
` For patients naïve to oral paliperidone or oral or injectable risperidone,
`
`
`
`
`
`
`
`
`
`
`
`
` establish tolerability with oral paliperidone or oral risperidone prior to
`
`
`
`
`
`
`
`
`
`
`
` initiating treatment with INVEGA SUSTENNA®. (2.2)
`
`
`
`
`
` Missed Doses: To manage either a missed second initiation dose or a
`
`
`
`
`
`
`
`
`
`
`
`
` missed monthly maintenance dose, refer to the Full Prescribing
`
`
`
`
`
`
`
`
` Information. (2.3)
`
`
` Moderate to severe renal impairment (creatinine clearance < 50 mL/min):
`
`
`
`
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® is not recommended. (2.5)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` ------------------------------ADVERSE REACTIONS-----------------------------
`
` The most common adverse reactions (incidence ≥ 5% and occurring at least
`
`
`
`
`
`
`
`
`
`
` twice as often as placebo) were injection site reactions, somnolence/sedation,
`
`
`
`
`
`
`
`
` dizziness, akathisia, and extrapyramidal disorder. (6)
`
`
`
`
`
`
`
`
`
`
`
`
` To report SUSPECTED ADVERSE REACTIONS, contact Janssen
`
`
`
` Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at
`
`
`
`
` 1-800-FDA-1088 or www.fda.gov/medwatch
`
`
`
`
`---------------------------------DRUG INTERACTIONS---------------------------
` Drugs that may cause orthostatic hypotension: An additive effect may
`
`
`
`
`
`
`
`
`
`
`
` occur when co-administered with INVEGA SUSTENNA®. (7.1)
`
`
`
`
`
`
`
` Strong CYP3A4/P-glycoprotein (P-gp) inducers: Avoid using a strong
`
`
`
`
`
`
`
` inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John’s
`
`
`
`
`
`
`
`
`
` Wort) during a dosing interval for INVEGA SUSTENNA®. If
`
`
`
`
`
`
`
`
` administering a strong inducer is necessary, consider managing the patient
`
`
`
`
` using paliperidone extended release tablets. (2.5, 7.1, 12.3)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` -----------------------USE IN SPECIFIC POPULATIONS----------------------
` Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in
`
`
`
`
`
`
`
` neonates with third trimester exposure. (8.1)
`
`
`
`
`
`
`
`
`
`
`
`
` See 17 for PATIENT COUNSELING INFORMATION and FDA-
` approved patient labeling.
`
`
`
`
`
`
`
`
` Revised: 12/2017
`
`
`
`
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
`
`
`7.1
`
`
`7.2
`
`Drugs Having Clinically Important Interactions
`
`
`
`
`
`
`
` with INVEGA SUSTENNA®
`
`
`
`Drugs Having No Clinically Important
`
`
`
`
`
`
`
` Interactions with INVEGA SUSTENNA®
`
`
`
`
`
`
`
` 8 USE IN SPECIFIC POPULATIONS
`
`
`
`
`Pregnancy
`
`8.1
`
`
`8.2
`Labor and Delivery
`
`
`
`
`
`8.3
`Nursing Mothers
`
`
`
`
`8.4
`Pediatric Use
`
`
`
`
`8.5
`Geriatric Use
`
`
`
`
`8.6
`Renal Impairment
`
`
`
`8.7
`Hepatic Impairment
`
`
`
`8.8
`Patients with Parkinson’s Disease or Lewy Body
`
`
`
`
`
`
`
`
`
`Dementia
`
`
`
`
` 9 DRUG ABUSE AND DEPENDENCE
`
`
`
`Controlled Substance
`
`9.1
`
`
`
`9.2
`Abuse
`
`
`
`9.3
`Dependence
`
`
`
`10 OVERDOSAGE
`
`
`10.1 Human Experience
`
`
`
`
`10.2 Management of Overdosage
`
`
`
`
`
`11 DESCRIPTION
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`12.1 Mechanism of Action
`
`
`
`
`12.2 Pharmacodynamics
`
`
`12.3 Pharmacokinetics
`
`
`
`
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of
`
`
`
`
`
`
`Fertility
`
`
`
`14 CLINICAL STUDIES
`
`
`14.1 Schizophrenia
`
`
`
`14.2 Schizoaffective Disorder
`
`
`
`
`
` 16 HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`
` 17 PATIENT COUNSELING INFORMATION
`
`
`
` *Sections or subsections omitted from the full prescribing information are not
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`5.2
`
`
` FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`
`
` WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS
` WITH DEMENTIA-RELATED PSYCHOSIS
`
`
`
`
`
` INDICATIONS AND USAGE
`1
`
`
`
`
` 2 DOSAGE AND ADMINISTRATION
`
`
`
`Administration Instructions
`
`2.1
`
`
`
`2.2
`Schizophrenia and Schizoaffective Disorder
`
`
`
`
`
`2.3
`Missed Doses
`
`
`
`
`2.4
`Use with Risperidone or with Oral Paliperidone
`
`
`
`
`
`
`
`
`2.5
`Dosage Adjustments
`
`
`
`
`2.6
`Switching from Other Antipsychotics
`
`
`
`
`
`
`2.7
`Instructions for Use
`
`
`
`
`
` 3 DOSAGE FORMS AND STRENGTHS
`
`
`
`
`4 CONTRAINDICATIONS
`
`
` 5 WARNINGS AND PRECAUTIONS
`
`
`Increased Mortality in Elderly Patients with
`
`5.1
`
`
`
`
`
`
`
`Dementia-Related Psychosis
`
`
`Cerebrovascular Adverse Reactions, Including
`
`
`
`
`
`Stroke, in Elderly Patients with Dementia-
`
`
`
`
`
`
`
`Related Psychosis
`
`
`
`
`Neuroleptic Malignant Syndrome
`
`5.3
`
`
`
`
`QT Prolongation
`
`5.4
`
`
`Tardive Dyskinesia
`
`5.5
`
`
`
`Metabolic Changes
`
`5.6
`
`
`
`Orthostatic Hypotension and Syncope
`
`5.7
`
`
`
`
`
`Falls
`
`5.8
`
`
`Leukopenia, Neutropenia, and Agranulocytosis
`
`5.9
`
`
`
`
`
`5.10 Hyperprolactinemia
`
`
`
`5.11 Potential for Cognitive and Motor Impairment
`
`
`
`
`
`
`
`5.12 Seizures
`
`
`
`5.13 Dysphagia
`
`
`
`5.14 Priapism
`
`
`
`5.15 Disruption of Body Temperature Regulation
`
`
`
`
`
`
`
` 6 ADVERSE REACTIONS
`
`
`
`Clinical Trials Experience
`
`6.1
`
`
`
`
`6.2
`Postmarketing Experience
`
`
`
`
`7 DRUG INTERACTIONS
`
`
`
`
` listed.
`
`Reference ID: 4198682
`
`
`
`
`
`
`FULL PRESCRIBING INFORMATION
`
`
`
`
`
`
`
`
`
` WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA
`RELATED PSYCHOSIS
`
`
` Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at
`
`
`
` an increased risk of death [see Warnings and Precautions (5.1)].
`
`
`
` INVEGA SUSTENNA® is not approved for use in patients with dementia-related
`
` psychosis [see Warnings and Precautions (5.1)].
`
`
`
`
`
`
`
`
`
`
`
` INDICATIONS AND USAGE
` 1
`
`
`
`INVEGA SUSTENNA® (paliperidone palmitate) is indicated for the treatment of:
`
`
`
` Schizophrenia in adults [see Clinical Studies (14.1)].
`
`
`
` Schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or
`
`
`
`
`
`
`
` antidepressants [see Clinical Studies (14.2)].
`
`
`
`
`
` 2 DOSAGE AND ADMINISTRATION
` 2.1 Administration Instructions
`
`
`
`
`
`
`
` Each injection must be administered only by a healthcare professional.
`
`
`
`
`
`
`
`
`
` Parenteral drug products should be inspected visually for foreign matter and discoloration prior to
`
`
`
`
`
`
`
` administration, whenever product and container permit.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® is intended for intramuscular use only. Do not administer by any other
`
`
`
`
`
`
`
`
`
` route. Avoid inadvertent injection into a blood vessel. Administer the dose in a single injection;
`
`
`
`
`
`
`
`
`
`
`
` do not administer the dose in divided injections. Inject slowly, deep into the deltoid or gluteal
`
`
`
`
`
` muscle.
`
` INVEGA SUSTENNA® must be administered using only the needles that are provided in the
`
`
` INVEGA SUSTENNA® kit.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` The recommended needle size for administration of INVEGA SUSTENNA® into the deltoid
`
`
`
`
`
` muscle is determined by the patient’s weight:
`
`
`
` For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
`
`
`
`
`
` For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended.
`
`
`
`
`
`
`
`
`
` Deltoid injections should be alternated between the two deltoid muscles.
`
`
`
`
`
`
`
`
`
` The recommended needle size for administration of INVEGA SUSTENNA® into the gluteal
`
`
`
`
`
` muscle is the 1½-inch, 22 gauge needle regardless of patient weight.
`
`
`
`
`
`
`
`
`
` Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be
`
`
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` alternated between the two gluteal muscles.
`
`
`
`
`
` 2.2 Schizophrenia and Schizoaffective Disorder
`
`
`
`
`
`
`
` For patients who have never taken oral paliperidone or oral or injectable risperidone, it is
`
`
`
`
`
` recommended to establish tolerability with oral paliperidone or oral risperidone prior to initiating
`
` treatment with INVEGA SUSTENNA®.
`
`
`
`
`
`
`
`
`
`
` The recommended dosing of INVEGA SUSTENNA® for each approved indication is displayed in
`
`
`
`
`
`
` Table 1. The recommended initiation of INVEGA SUSTENNA® is with a dose of 234 mg on
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. Following
`
`
`
`
`
`
`
`
`
` the second initiation dose, monthly maintenance doses can be administered in either the deltoid or
`
`
`
`
`
` gluteal muscle.
`
`
`
`Table 1:
`
`
`
`Recommended Dosing of INVEGA SUSTENNA for Adults with Schizophrenia or
`
`
`
`
`
`Schizoaffective Disorder
`
`
`
`
`
` Indication
`
` Schizophrenia
`
`
`
` Initiation Dosing
`
`
`
` (deltoid)
`
`
`
` Day 1
`
`
`
` Day 8
`
`
`
` 234 mg
`
`
`
`
`
` 156 mg
`
`
`
` Monthly
`
` Maintenance Dosea
`
`
`
`
`
` (deltoid or gluteal)
`
`
`
`
`
` Maximum
`
`
`
` Monthly Dose
`
`
`
`
`
` 234 mg
`
`
`
`
`
`
`
` Schizoaffective disorder
`
`
`
` 234 mg
`
`
`
`
` 39-234 mgb
`
`
`
`
` 78-234 mgc
`
`
`
`
`
` 156 mg
`
`
`
`
`
` 234 mg
`
`
`
`
`
` b
`
`
`
`
` a Administered 5 weeks after the first injection.
`
`
`
`
`
`
`
`
`
` The recommended maintenance dose for treatment of schizophrenia is 117 mg. Some patients may benefit
`
`
`
`
` from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg,
`
`
`
`
`
`
`
`
`
`
`
`
`
` and 234 mg).
`
`
`
` c Adjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not
`
`
`
`
`
`
`
`
`
` studied in the long-term schizoaffective disorder study.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the
`
`
`
`
`
`
`
` prolonged-release characteristics of INVEGA SUSTENNA® should be considered [see Clinical
`
` Pharmacology (12.3)], as the full effect of the dose adjustment may not be evident for several
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` months.
`
`
`
`
`
`
`
` 2.3 Missed Doses
`
`
` Avoiding Missed Doses
`
` It is recommended that the second initiation dose of INVEGA SUSTENNA® be given one week
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` after the first dose. To avoid a missed dose, patients may be given the second dose 4 days before
`
`
`
`
`
`
`
`
`
`
`
` or after the one-week time point. Similarly, the third and subsequent injections after the initiation
`
` regimen are recommended to be given monthly. To avoid a missed monthly dose, patients may be
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` given the injection up to 7 days before or after the monthly time point.
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` Management of a Missed Second Initiation Dose
`
`
` If the target date for the second INVEGA SUSTENNA® injection (one week ± 4 days) is missed,
`
`
`
`
`
`
`
`
`
`
`
` the recommended reinitiation depends on the length of time which has elapsed since the patient's
`
`
`
`
`
`
`
`
`
` first injection. In case of a missed second initiation dose follow the dosing instructions provided
`
`
`
`
`
`
`
` in Table 2.
`
`
`
`
`
` Table 2:
`
`
`
`
`
`
`
`
`
` Management of a Missed Second Initiation Dose
`
`
`
`
`
`
`
` TIMING OF MISSED SECOND
`
`
`
` INITIATION DOSE
`
`
`
` DOSING
`
` Less than 4 weeks since first injection
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Administer the second initiation dose of 156 mg in the deltoid
`
`
`
`
`
`
`
` It is recommended to administer a third injection of 117 mg in
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` muscle as soon as possible.
`
`1.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` either the deltoid or gluteal muscle 5 weeks after the first injection
`
`
`
`
`
`
`
`
`
`
`
` (regardless of the timing of the second injection).
`
`
`
`
`
`
`
`
`
`
`
` 4 to 7 weeks since first injection
`
`
`
`
`
`
` 2. Thereafter, resume regular monthly dosing in either the deltoid or
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` gluteal muscle.
`
`
`
`
`
`
`
`
`
`
`
`
`
` Resume dosing with two injections of 156 mg in the following
`
`
`
`
`
` manner:
`
`
`
`
`
`
`
`
`
`
`
` More than 7 weeks since first injection Restart dosing with recommended initiation (see Section 2.2,
`
`
`
`
`
` 1. Administer a deltoid injection as soon as possible.
`
`
` 2. Administer a second deltoid injection 1 week later.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 3. Thereafter, resume regular monthly dosing in either the
`
`
`
`
`
`
`
`
`
`
`
`
`
` deltoid or gluteal muscle.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Table 1):
`
`
` 1. Administer a 234 mg deltoid injection on Day 1.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 2. Administer a 156 mg deltoid injection 1 week later.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 3. Thereafter, resume regular monthly dosing in either the
`
`
`
`
`
`
`
` deltoid or gluteal muscle.
`
`
`
`
`
`
`
`
` Management of a Missed Maintenance Dose
`
`
`
`
`
` In case of a missed maintenance dose follow the dosing instructions provided in Table 3.
`
`
`
`
`
` Table 3:
`
`
`
`
`
`
`
` Management of a Missed Maintenance Dose
`
`
`
`
`
`
`
` TIMING OF MISSED
`
`
`
` MAINTENANCE DOSE
`
`
`
`
`
` DOSING
`
`
`
`
`
` 4 to 6 weeks since last injection
`
`
`
`
`
`
`
`
`
`
`
` Resume regular monthly dosing as soon as possible at the patient’s
`
`
`
`
`
`
`
`
`
` previously stabilized dose, followed by injections at monthly
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` intervals.
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` More than 6 weeks to 6 months since
`
`
`
`
`
`
`
`
`
`
`
`
`
` Resume the same dose the patient was previously stabilized on
`
`
`
`
`
` last injection
`
`
`
`
`
`
`
` (unless the patient was stabilized on a dose of 234 mg, then the first
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 2 injections should each be 156 mg) in the following manner:
`
`
`
`
`
`
` 1. Administer a deltoid injection as soon as possible.
`
`
`
`
`
`
`
`
`
`
`
`
` 2. Administer a second deltoid injection 1 week later at the same
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` dose.
`
`
` 3. Thereafter, resume administering the previously stabilized
`
`
`
`
`
`
`
`
`
` dose in the deltoid or gluteal muscle 1 month after the second
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` injection.
`
`
`
`
`
`
`
`
`
` More than 6 months since last injection Restart dosing with recommended initiation (see Section 2.2,
`
`
`
`
`
`
`
`
`
`
` Table 1):
`
`
` 1. Administer a 234 mg deltoid injection on Day 1.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 2. Administer a 156 mg deltoid injection 1 week later.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 3. Thereafter, resume administering the previously stabilized
`
`
`
`
`
`
`
`
`
` dose in the deltoid or gluteal muscle 1 month after the second
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` injection.
`
`
`
`
`
`
`
` 2.4 Use with Risperidone or with Oral Paliperidone
`
`
`
`
`
` Since paliperidone is the major active metabolite of risperidone, caution should be exercised when
`
`
`
`
`
`
` INVEGA SUSTENNA® is coadministered with risperidone or with oral paliperidone for extended
`
`
`
`
`
`
` periods of time. Safety data involving concomitant use of INVEGA SUSTENNA® with other
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` antipsychotics is limited.
`
` 2.5 Dosage Adjustments
`
`
`
` Renal Impairment
` INVEGA SUSTENNA® has not been systematically studied in patients with renal impairment [see
`
` Clinical Pharmacology (12.3)]. For patients with mild renal impairment (creatinine clearance ≥
`
`
`
` 50 mL/min to < 80 mL/min [Cockcroft-Gault Formula]), initiate INVEGA SUSTENNA® with a
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` dose of 156 mg on treatment day 1 and 117 mg one week later. Administer both doses in the deltoid
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` muscle. Thereafter, follow with monthly injections of 78 mg in either the deltoid or gluteal muscle
`
`
`
`
`
` [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
`
`
`
`
`
`
`
`
`
`
`
`
`
` INVEGA SUSTENNA® is not recommended in patients with moderate or severe renal impairment
` (creatinine clearance < 50 mL/min) [see Use in Specific Populations (8.6) and Clinical
`
`
`
`
`
`
`
`
`
`
`
` Pharmacology (12.3)].
`
`
`
` Coadministration with Strong CYP3A4/P-glycoprotein (P-gp) Inducers
`
`
`
` Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John’s
`
`
`
`
`
`
` Wort) during the 1-month dosing interval for INVEGA SUSTENNA®, if possible. If administering
`
`
` a strong inducer is necessary, consider managing the patient using paliperidone extended release
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
` tablets [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
`
`
`
`
`
` 2.6 Switching from Other Antipsychotics
`
`
`
`
`
` There are no systematically collected data to specifically address switching patients with
`
`
`
`
`
`
`
` schizophrenia or schizoaffective disorder from other antipsychotics to INVEGA SUSTENNA®, or
`
`
`
`
`
`
`
`
`
`
`
`
` concerning concomitant administration with other antipsychotics.
`
`
`
`
`
` Switching from Oral Antipsychotics
`
`
`
`
`
`
`
` For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability
`
`
`
` should be established with oral paliperidone or oral risperidone prior to initiating treatment with
`
` INVEGA SUSTENNA®.
`
`
`
`
`
`
`
`
`
`
`
`
` Previous oral antipsychotics can be gradually discontinued at the time of initiation of treatment
`
`
`
`
` with INVEGA SUSTENNA®. Recommended initiation of INVEGA SUSTENNA® is with a dose
`
`
`
`
`
`
`
`
`
`
`
`
` of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` [see Dosage and Administration (2.2)]. Patients previously stabilized on different doses of
`
`
`
`
` INVEGA® Extended-Release tablets can attain similar paliperidone steady-state exposure during
`
`
`
`
` maintenance treatment with INVEGA SUSTENNA® monthly doses as depicted in Table 4.
`
`
`
`
`
`
`
`
`Table 4:
`
`
`
`
`
` Formulation
`
`
`
`
`
`
`
`
`
`Doses of INVEGA and INVEGA SUSTENNA Needed to Attain Similar Steady-State
`
`
`
`
`
`
`Paliperidone Exposure During Maintenance Treatment
`
`
`
` INVEGA®
`
` Extended-Release Tablet
`
` Once Daily
`
` 12
`
` 9
`
` 6
`
` 3
`
`
`
` Dosing Frequency
`
` Dose (mg)
`
`
`
` INVEGA SUSTENNA®
`
` Injection
` Once every 4 weeks
`
`
`
` 234
`
` 156
`
` 117
` 39-78
`
`
`
` Switching from Long-Acting Injectable Antipsychotics
`
`
`
`
`
`
`
`
`
`
`
` For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability
`
`
`
` should be established with oral paliperidone or oral risperidone prior to initiating treatment with
`
` INVEGA SUSTENNA®.
`
`
`
`
`
`
`
`
`
`
`
`
` When switching patients currently at steady-state on a long-acting injectable antipsychotic, initiate
`
`
`
`
`
`
` INVEGA SUSTENNA® therapy in place of the next scheduled injection. INVEGA SUSTENNA®
`
`
`
` should then be continued at monthly intervals. The one-week initiation dosing regimen as
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` described in Section 2.2 is not required. See Table 1 above for recommended monthly maintenance
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` dosing. Based on previous clinical history of tolerability and/or efficacy, some patients may benefit
`
`
`
`
`
`
`
`
`
`
`
` from lower or higher maintenance doses within the available strengths (39 mg, 78 mg, 117 mg,
`
`
`
`
`
`
`
`
`
`
`
`
`
` 156 mg, and 234 mg). The 39 mg strength was not studied in the long-term schizoaffective disorder
`
`
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` study. Monthly maintenance doses can be administered in either the deltoid or gluteal muscle [see
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Dosage and Administration (2.2)].
`
`
`
`
`
`
`
`
`
` If INVEGA SUSTENNA® is discontinued, its prolonged-release characteristics must be
`
`
`
`
`
`
`
`
`
`
`
`
`
` considered. As recommended with other antipsychotic medications, the need for continuing
`
`
`
`
`
` existing extrapyramidal symptoms (EPS) medication should be re-evaluated periodically.
`
`
`
` 2.7
`
`
`
` Instructions for Use
`
`
`
`
`
` Each injection must be administered only by a healthcare professional.
`
`The kit contains a prefilled syringe and 2 safety needles (a 1 ½-inch 22 gauge needle and a 1-inch
`
`
`
` 23 gauge needle) for intramuscular injection.
`
`
`
`
`
` INVEGA SUSTENNA® is for single use only.
`
`
`
`
`
`a. Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous
`
`
`
`
`
`
`
`
`
` suspension.
`
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
`
`
`
` b. Select the appropriate needle.
`
`
`
`
`
` For DELTOID injection:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` If the patient weighs less than 90 kg, use the 1-inch 23 gauge needle (needle with blue
`
`
`
`
`
` colored hub).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` If the patient weighs 90 kg or more, use the 1 ½-inch 22 gauge needle (needle with gray
`
`
`
`
`
` colored hub).
`
`
`
` For GLUTEAL injection:
`
`
`
`
`
`
`
`
`
`
`
`
`
` Use the 1 ½-inch 22 gauge needle (needle with gray colored hub) regardless of patient’s
`
`
`
`
`
` weight.
`
`
`
` c. While holding the syringe upright, remove the rubber tip cap with an easy clockwise twisting
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` motion.
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
` d. Peel the safety needle pouch half way open. Grasp the needle sheath using the plastic peel
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` pouch. Attach the safety needle to the luer connection of the syringe with an easy clockwise
`
`
`
`
`
` twisting motion.
`
`
`
`
`
` e. Pull the needle sheath away from the needle with a straight pull. Do not twist the sheath as the
`
`
`
`
`
`
`
`
`
`
`
` needle may be loosened from the syringe.
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` f. Bring the syringe with the attached needle in upright position to de-aerate. De-aerate the
`
`
`
`
`
`
`
`
`
`
`
` syringe by moving the plunger rod carefully forward.
`
`
`
`
`
`
`
`
`
`
`
`
`
` g. Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal
`
`
`
`
`
` muscle of the patient. Do not administer by any other route.
`
` h. After the injection is complete, use either thumb or finger of one hand (h1, h2) or a flat surface
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` (h3) to activate the needle protection system. The needle protection system is fully activated
`
`
`
`
`
`
`
` when a ‘click’ is heard. Discard the syringe with needle appropriately.
`
`
`
` h1
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
`
`
`h2
`
`
`
` h3
`
`
`
`
`
` 3 DOSAGE FORMS AND STRENGTHS
`
`
` INVEGA SUSTENNA® is available as a white to off-white aqueous extended-release injectable
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` suspension for intramuscular injection in dose strengths of 39 mg, 78 mg, 117 mg, 156 mg, and
`
`
`
`
`
`
`
`
`
` 234 mg paliperidone palmitate.
`
`
`
` 4 CONTRAINDICATIONS
`
`
` INVEGA SUSTENNA® is contraindicated in patients with a known hypersensitivity to either
`
`
`
`
`
` paliperidone or risperidone, or to any of the excipients in the INVEGA SUSTENNA® formulation.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported
`
`
`
`
`
`
`
`
`
`
`
`
`
` in patients treated with risperidone and in patients treated with paliperidone. Paliperidone palmitate
`
`
`
`
`
` is converted to paliperidone, which is a metabolite of risperidone.
`
`
`
`
` 5 WARNINGS AND PRECAUTIONS
`
`
` 5.1
`
` Increased Mortality in Elderly Patients with Dementia-Related Psychosis
`
`
`
`
`
`
`
` Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an
`
`
`
`
`
`
`
`
`
`
`
` increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks),
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated
`
`
`
`
`
` patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%,
`
`
`
`
`
`
`
` compared to a rate of about 2.6% in the placebo group.
`
`
`
` Although the causes of death were varied, most of the deaths appeared to be either cardiovascular
`
`
`
`
`
`
`
` (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies
`
`
`
`
`
` suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic
`
`
`
`
`
`
`
`
`
` drugs may increase mortality. The extent to which the findings of increased mortality in
`
`
`
`
`
` observational studies may be attributed to the antipsychotic drug as opposed to some
`
`
`
`
` characteristic(s) of the patients is not clear. INVEGA SUSTENNA® is not approved for the
`
` treatment of patients with dementia-related psychosis [see Boxed Warning and Warnings and
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Precautions (5.2)].
`
`5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients
`
`
`
`
` with Dementia-Related Psychosis
`
`
`In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with
`
`
`
`
`
`
`
`
`
` dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular
`
`
`
`
`
`
`
` accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects.
`
` No studies have been conducted with oral paliperidone, INVEGA SUSTENNA®, or the 3-month
`
`
`
`
`
`
`
`
`
`
`
`
` paliperidone palmitate extended-release injectable suspension in elderly patients with dementia.
`
`
`
`
`
`
`
`
`
` These medicines are not approved for the treatment of patients with dementia-related psychosis
`
`
`
`
`
`
`
`
`
` [see Boxed Warning and Warnings and Precautions (5.1)].
`
`5.3 Neuroleptic Malignant Syndrome
`
`
` A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome
`
`
`
`
`
`
`
`
`
` (NMS) has been reported in association with antipsychotic drugs, including paliperidone.
`
`
`
` Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and
`
`
`
`
`
`
`
` evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and
`
`
`
` cardiac dysrhythmia). Additional signs may
`
`
`
`
`
` include elevated creatine phosphokinase,
`
`
`
`
`
` myoglobinuria (rhabdomyolysis), and acute renal failure.
`
`
`
`
`
`
`
` The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis,
`
`
`
`
`
` it is important to identify cases in which the clinical presentation includes both serious medical
`
`
`
`
`
` illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated
`
`
`
`
`
`
`
`
`
`
`
`
`
` extrapyramidal signs and symptoms (EPS). Other important considerations in the differential
`
`
`
` diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central
`
`
`
`
`
`
`
` nervous system pathology.
`
`
`
` The management of NMS should include: (1) immediate discontinuation of antipsychotic drugs
`
`
`
`
`
`
`
`
`
` and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and
`
`
`
`
`
`Reference ID: 4198682
`
`
`
`
`
`
` medical monitoring; and (3) treatment of any concomitant serious medical problems for which
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` specific treatments are available. There is no general agreement about specific pharmacological
`
`
`
`
`
`
`
` treatment regimens for uncomplicated NMS.
`
`
`
`
`
`
`
`
`
` If a patient appears to require antipsychotic drug treatment after recovery from NMS,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` reintroduction of drug therapy should be closely monitored, since recurrences of NMS have been
`
`
`
`
`
`
`
`
`
`
`
` reported.
`
`
`
` 5.4 QT Prolongation
`
`
`
`
`
`
`
`
`
`
`
` Paliperidone causes a modest increase in the corrected QT (QTc) interval. The use of paliperidone
`
`
`
`
`
`
`
` should be avoided in combination with other drugs that are known to prolong QTc including Class
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic
`
`
`
`
`
` medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g.,
`
`
`
`
`
`
`
` gatifloxacin,