HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`RISPERDAL CONSTA® safely and effectively. See full prescribing
`information for RISPERDAL CONSTA®.
`CONSTA®
`RISPERDAL
`(risperidone)
`INJECTION
`Initial U.S. Approval: 2003
`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. RISPERDAL
`CONSTA® is not approved for use in patients with dementia-related
`psychosis. (5.1)
`
`LONG-ACTING
`
`•
`
`•
`
`•
`
`•
`
`----------------------------RECENT MAJOR CHANGES-----------------------
`Warnings and Precautions (5.8)
`
`
`02/2017
`—————————INDICATIONS AND USAGE————————
`RISPERDAL CONSTA® is an atypical antipsychotic indicated:
`for the treatment of schizophrenia. (1.1)
`•
`as monotherapy or as adjunctive therapy to lithium or valproate for the
`•
`maintenance treatment of Bipolar I Disorder. (1.2)
`——————— DOSAGE AND ADMINISTRATION———————
`For patients who have never taken oral RISPERDAL®, tolerability
`•
`should be established with oral RISPERDAL® prior to initiating
`treatment with RISPERDAL CONSTA®. (2)
`Administer by deep intramuscular (IM) deltoid or gluteal injection.
`Each injection should be administered by a health care professional
`using the appropriate enclosed safety needle (1-inch for deltoid
`administration alternating injections between the two arms and 2-inch
`for gluteal administration alternating injections between the two
`buttocks). Do not administer intravenously. (2)
`25 mg intramuscular (IM) every 2 weeks. Patients not responding to
`25 mg may benefit from a higher dose of 37.5 mg or 50 mg. The
`maximum dose should not exceed 50 mg every 2 weeks. (2)
`Oral RISPERDAL® (or another antipsychotic medication) should be
`given with the first injection of RISPERDAL CONSTA®, and
`continued for 3 weeks (and then discontinued) to ensure adequate
`therapeutic plasma concentrations from RISPERDAL CONSTA®. (2)
`Upward dose adjustment of RISPERDAL CONSTA® should not be
`made more frequently than every 4 weeks. Clinical effects of each
`upward dose adjustment should not be anticipated earlier than 3 weeks
`after injection. (2)
`Avoid inadvertent administration into a blood vessel. (5.16)
`•
`See Full Prescribing Information Section 2.8 for instructions for use.
`•
`——————— DOSAGE FORMS AND STRENGTHS——————
`Vial kits: 12.5 mg, 25 mg, 37.5 mg, and 50 mg (3)
`—————————— CONTRAINDICATIONS—————————
`Known hypersensitivity to risperidone, paliperidone, or to any
`•
`excipients in RISPERDAL CONSTA®. (4)
`——————— WARNINGS AND PRECAUTIONS———————
`Cerebrovascular events, including stroke, in elderly patients with
`•
`dementia-related psychosis. RISPERDAL CONSTA®
`is not
`approved for use in patients with dementia-related psychosis (5.2)
`Neuroleptic Malignant Syndrome: Manage with
`immediate
`discontinuation and close monitoring (5.3)
`Tardive Dyskinesia: Discontinue treatment if clinically appropriate
`(5.4)
`• Metabolic Changes: Atypical antipsychotic drugs have been
`associated with metabolic changes that may increase cardiovascular/
`cerebrovascular
`risk.
`These metabolic
`changes
`include
`hyperglycemia, dyslipidemia, and weight gain. (5.5)
`o Hyperglycemia and Diabetes Mellitus: Monitor patients for
`symptoms of hyperglycemia
`including polydipsia, polyuria,
`polyphagia, and weakness. Monitor glucose regularly in patients
`with diabetes or at risk for diabetes. (5.5)
`o Dyslipidemia: Undesirable alterations have been observed in
`patients treated with atypical antipsychotics. (5.5)
`o Weight Gain: Significant weight gain has been reported. Monitor
`weight gain. (5.5)
`Hyperprolactinemia: Risperidone treatment may elevate prolactin
`levels. Long-standing hyperprolactinemia, when associated with
`
`•
`
`•
`
`•
`
`Reference ID: 4060013
`
`1
`
`hypogonadism, can lead to decreased bone density in men and
`women. (5.6)
`Orthostatic hypotension: associated with dizziness, tachycardia,
`bradycardia, and syncope can occur, especially during initial dose
`titration with oral risperidone. Use caution
`in patients with
`cardiovascular disease, cerebrovascular disease, and conditions that
`could affect hemodynamic responses. (5.7)
`Leukopenia, Neutropenia, and Agranulocytosis have been reported
`with antipsychotics, including RISPERDAL CONSTA®. Patients
`with history of a clinically significant low white blood cell count
`(WBC) or a drug-induced leukopenia/neutropenia should have their
`complete blood cell count (CBC) monitored frequently during the
`first few months of therapy and discontinuation of RISPERDAL
`CONSTA® should be considered at the first sign of a clinically
`significant decline in WBC in the absence of other causative
`factors. (5.9)
`Potential for cognitive and motor impairment: has potential to impair
`judgment, thinking, and motor skills. Use caution when operating
`machinery, including automobiles. (5.10)
`Seizures: Use cautiously in patients with a history of seizures or with
`conditions that potentially lower the seizure threshold. (5.11)
`Dysphagia: Esophageal dysmotility and aspiration can occur. Use
`cautiously in patients at risk for aspiration pneumonia. (5.12)
`Priapism: has been reported. Severe priapism may require surgical
`intervention. (5.13)
`Thrombotic Thrombocytopenic Purpura (TTP): has been reported.
`(5.14)
`Avoid inadvertent administration into a blood vessel. (5.16)
`Suicide: There is increased risk of suicide attempt in patients with
`schizophrenia or bipolar disorder, and close supervision of high-risk
`patients should accompany drug therapy. (5.17)
`Increased sensitivity in patients with Parkinson’s disease or those
`with dementia with Lewy bodies: has been reported. Manifestations
`include mental status changes, motor impairment, extrapyramidal
`symptoms, and features consistent with Neuroleptic Malignant
`Syndrome. (5.19)
`Diseases or conditions that could affect metabolism or hemodynamic
`responses: Use with caution in patients with such medical conditions
`(e.g., recent myocardial infarction or unstable cardiac disease). (5.19)
`—————————— ADVERSE REACTIONS—————————
`The most common adverse reactions in clinical trials in patients with
`schizophrenia (≥ 5%) were headache, parkinsonism, dizziness, akathisia,
`fatigue, constipation, dyspepsia, sedation, weight increased, pain in
`extremity, and dry mouth. The most common adverse reactions in clinical
`trials in patients with bipolar disorder were weight increased (5% in
`monotherapy trial) and tremor and parkinsonism (≥ 10% in adjunctive
`therapy trial). (6)
`that were associated with
`reactions
`The most common adverse
`discontinuation from clinical trials in patients with schizophrenia were
`agitation, depression, anxiety, and akathisia. Adverse reactions that were
`associated with discontinuation
`from bipolar disorder
`trials were
`hyperglycemia (one subject monotherapy trial) and hypokinesia and tardive
`dyskinesia (one subject each in adjunctive therapy trial). (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—————————
`Due to CNS effects, use caution when administering with other
`•
`centrally-acting drugs. Avoid alcohol. (7.1)
`Due to hypotensive effects, hypotensive effects of other drugs with
`this potential may be enhanced. (7.2)
`Effects of levodopa and dopamine agonists may be antagonized.
`(7.3)
`Cimetidine and ranitidine increase the bioavailability of risperidone.
`(7.5)
`Clozapine may decrease clearance of risperidone. (7.6)
`Fluoxetine and paroxetine
`increase plasma concentrations of
`risperidone. (7.11)
`Carbamazepine and other enzyme
`concentrations of risperidone. (7.12)
`——————— USE IN SPECIFIC POPULATIONS———————
`Renal or Hepatic Impairment: dose appropriately with oral
`•
`RISPERDAL® prior to initiating treatment with RISPERDAL
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`
`•
`•
`
`•
`
`inducers decrease plasma
`
`ALKERMES Exh. 2071
`Luye v. Alkermes
`IPR2016-1096
`
`

`

`CONSTA®. A lower starting dose of RISPERDAL CONSTA® of
`12.5 mg may be appropriate in some patients. (2.4)
`Nursing Mothers: should not breast feed. (8.3)
`Pediatric Use: safety and effectiveness not established in patients
`less than 18 years of age. (8.4)
`
`•
`
`Elderly: dosing for otherwise healthy elderly patients is the same
`as for healthy nonelderly. Elderly may be more predisposed to
`orthostatic effects than nonelderly. (8.5)
`See 17 for PATIENT COUNSELING INFORMATION
`Revised: 02/2017
`
`
`
`
`•
`•
`
`
`
`
`
`Reference ID: 4060013
`
`2
`
`

`

`6.6 Changes in ECG
`6.7 Pain Assessment and Local Injection Site
`Reactions
`6.8 Postmarketing Experience
`7 DRUG INTERACTIONS
`7.1 Centrally-Acting Drugs and Alcohol
`7.2 Drugs with Hypotensive Effects
`7.3
`Levodopa and Dopamine Agonists
`7.4 Amitriptyline
`7.5 Cimetidine and Ranitidine
`7.6 Clozapine
`7.7
`Lithium
`7.8 Valproate
`7.9 Digoxin
`7.10 Topiramate
`7.11 Drugs That Inhibit CYP 2D6 and Other CYP
`Isozymes
`7.12 Carbamazepine and Other CYP 3A4 Enzyme
`Inducers
`7.13 Drugs Metabolized by CYP 2D6
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2
`Labor and Delivery
`8.3 Nursing Mothers
`8.4 Pediatric Use
`8.5 Geriatric Use
`9 DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`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 Bipolar Disorder - Monotherapy
`14.3 Bipolar Disorder - Adjunctive Therapy
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`17.1 Orthostatic Hypotension
`17.2 Interference with Cognitive and Motor
`Performance
`17.3 Pregnancy
`17.4 Nursing
`17.5 Concomitant Medication
`17.6 Alcohol
`
`
`
`*Sections or subsections omitted from the full prescribing information are
`not listed.
`
`1
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`WARNING: INCREASED MORTALITY IN ELDERLY
`PATIENTS WITH DEMENTIA-RELATED
`PSYCHOSIS
`INDICATIONS AND USAGE
`1.1 Schizophrenia
`1.2 Bipolar Disorder
`2 DOSAGE AND ADMINISTRATION
`2.1 Schizophrenia
`2.2 Bipolar Disorder
`2.3 General Dosing Information
`2.4 Dosage in Special Populations
`2.5 Reinitiation of Treatment in Patients Previously
`Discontinued
`2.6 Switching from Other Antipsychotics
`2.7 Co-Administration of RISPERDAL CONSTA®
`with Certain Other Medications
`2.8
`Instructions for Use
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1
`Increased Mortality in Elderly Patients with
`Dementia-Related Psychosis
`5.2 Cerebrovascular Adverse Events, Including
`Stroke, in Elderly Patients with Dementia-
`Related Psychosis
`5.3 Neuroleptic Malignant Syndrome (NMS)
`5.4 Tardive Dyskinesia
`5.5 Metabolic Changes
`5.6 Hyperprolactinemia
`5.7 Orthostatic Hypotension
`5.8 Falls
`5.9
`Leukopenia, Neutropenia, and Agranulocytosis
`5.10 Potential for Cognitive and Motor Impairment
`5.11 Seizures
`5.12 Dysphagia
`5.13 Priapism
`5.14 Thrombotic Thrombocytopenic Purpura (TTP)
`5.15 Body Temperature Regulation
`5.16 Administration
`5.17 Antiemetic Effect
`5.18 Suicide
`5.19 Use in Patients with Concomitant Illness
`5.20 Osteodystrophy and Tumors in Animals
`5.21 Monitoring: Laboratory Tests
`6 ADVERSE REACTIONS
`6.1 Commonly-Observed Adverse Reactions in
`Double-Blind, Placebo-Controlled Clinical Trials
`- Schizophrenia
`6.2 Commonly-Observed Adverse Reactions in
`Double-Blind, Placebo-Controlled Clinical Trials
`– Bipolar Disorder
`6.3 Other Adverse Reactions Observed During the
`Clinical Trial Evaluation of Risperidone
`6.4 Discontinuations Due to Adverse Reactions
`6.5 Dose Dependency of Adverse Reactions in
`Clinical Trials
`
`3
`
`
`
`
`
`Reference ID: 4060013
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`

`

`
`
`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. 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 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. RISPERDAL CONSTA®
`(risperidone) is not approved for the treatment of patients with dementia-related psychosis.
`[see Warnings and Precautions (5.1)]
`1
`INDICATIONS AND USAGE
`1.1 Schizophrenia
`RISPERDAL CONSTA® (risperidone) is indicated for the treatment of schizophrenia [see
`Clinical Studies (14.1)].
`
`1.2 Bipolar Disorder
`RISPERDAL CONSTA® is indicated as monotherapy or as adjunctive therapy to lithium or
`valproate for the maintenance treatment of Bipolar I Disorder [see Clinical Studies (14.2, 14.3)].
`
`2 DOSAGE AND ADMINISTRATION
`For patients who have never taken oral RISPERDAL®, it is recommended to establish
`tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®.
`
`RISPERDAL CONSTA® should be administered every 2 weeks by deep intramuscular (IM)
`deltoid or gluteal injection. Each injection should be administered by a health care professional
`using the appropriate enclosed safety needle [see Dosage and Administration (2.8)]. For deltoid
`administration, use the 1-inch needle alternating injections between the two arms. For gluteal
`administration, use the 2-inch needle alternating injections between the two buttocks. Do not
`administer intravenously.
`
`2.1 Schizophrenia
`The recommended dose for the treatment of schizophrenia is 25 mg IM every 2 weeks. Although
`dose response for effectiveness has not been established for RISPERDAL CONSTA®, some
`patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg. The
`
`Reference ID: 4060013
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`

`
`
`maximum dose should not exceed 50 mg RISPERDAL CONSTA® every 2 weeks. No additional
`benefit was observed with dosages greater than 50 mg RISPERDAL CONSTA®; however, a
`higher incidence of adverse effects was observed.
`
`The efficacy of RISPERDAL CONSTA® in the treatment of schizophrenia has not been
`evaluated in controlled clinical trials for longer than 12 weeks. Although controlled studies have
`not been conducted to answer the question of how long patients with schizophrenia should be
`treated with RISPERDAL CONSTA®, oral risperidone has been shown to be effective in
`delaying time to relapse in longer-term use. It is recommended that responding patients be
`continued on treatment with RISPERDAL CONSTA® at the lowest dose needed. The physician
`who elects to use RISPERDAL CONSTA® for extended periods should periodically re-evaluate
`the long-term risks and benefits of the drug for the individual patient.
`
`2.2 Bipolar Disorder
`The recommended dose for monotherapy or adjunctive therapy to lithium or valproate for the
`maintenance treatment of Bipolar I Disorder is 25 mg IM every 2 weeks. Some patients may
`benefit from a higher dose of 37.5 mg or 50 mg. Dosages above 50 mg have not been studied in
`this population. The physician who elects to use RISPERDAL CONSTA® for extended periods
`should periodically re-evaluate the long-term risks and benefits of the drug for the individual
`patient.
`
`2.3 General Dosing Information
`A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose
`adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that
`increase risperidone plasma concentrations [see Drug Interactions (7.11)] or in patients who
`have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5 mg dose
`has not been investigated in clinical trials.
`
`Oral RISPERDAL® (or another antipsychotic medication) should be given with the first injection
`of RISPERDAL CONSTA® and continued for 3 weeks (and then discontinued) to ensure that
`adequate therapeutic plasma concentrations are maintained prior to the main release phase of
`risperidone from the injection site [see Clinical Pharmacology (12.3)].
`
`Upward dose adjustment should not be made more frequently than every 4 weeks. The clinical
`effects of this dose adjustment should not be anticipated earlier than 3 weeks after the first
`injection with the higher dose.
`
`In patients with clinical factors such as hepatic or renal impairment or certain drug interactions
`that increase risperidone plasma concentrations [see Drug Interactions (7.11)], dose reduction as
`
`Reference ID: 4060013
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`

`
`
`low as 12.5 mg may be appropriate. The efficacy of the 12.5 mg dose has not been investigated
`in clinical trials.
`
`Do not combine two different dose strengths of RISPERDAL CONSTA® in a single
`administration.
`
`2.4 Dosage in Special Populations
`Elderly
`For elderly patients treated with RISPERDAL CONSTA®, the recommended dosage is 25 mg
`IM every 2 weeks. Oral RISPERDAL® (or another antipsychotic medication) should be given
`with the first injection of RISPERDAL CONSTA® and should be continued for 3 weeks to
`ensure that adequate therapeutic plasma concentrations are maintained prior to the main release
`phase of risperidone from the injection site [see Clinical Pharmacology (12.3)].
`
`Renal or Hepatic Impairment
`Patients with renal or hepatic impairment should be treated with titrated doses of oral
`RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®. The recommended
`starting dose is 0.5 mg oral RISPERDAL® twice daily during the first week, which can be
`increased to 1 mg twice daily or 2 mg once daily during the second week. If a total daily dose of
`at least 2 mg oral RISPERDAL® is well tolerated, an injection of 25 mg RISPERDAL
`CONSTA® can be administered every 2 weeks. Oral supplementation should be continued for
`3 weeks after the first injection until the main release of risperidone from the injection site has
`begun. In some patients, slower titration may be medically appropriate. Alternatively, a starting
`dose of RISPERDAL CONSTA® of 12.5 mg may be appropriate. The efficacy of the 12.5 mg
`dose has not been investigated in clinical trials.
`
`Patients with renal impairment may have less ability to eliminate risperidone than normal adults.
`Patients with impaired hepatic function may have an increase in the free fraction of the
`risperidone, possibly resulting in an enhanced effect [see Clinical Pharmacology (12.3)]. Elderly
`patients and patients with a predisposition to hypotensive reactions or for whom such reactions
`would pose a particular risk should be instructed in nonpharmacologic interventions that help to
`reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several
`minutes before attempting to stand in the morning and slowly rising from a seated position).
`These patients should avoid sodium depletion or dehydration, and circumstances that accentuate
`hypotension (alcohol intake, high ambient temperature, etc.). Monitoring of orthostatic vital
`signs should be considered [see Warnings and Precautions (5.7)].
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`Reference ID: 4060013
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`

`
`
`2.5 Reinitiation of Treatment in Patients Previously Discontinued
`There are no data to specifically address reinitiation of treatment. When restarting patients who
`have had an interval off treatment with RISPERDAL CONSTA®, supplementation with oral
`RISPERDAL® (or another antipsychotic medication) should be administered.
`
`2.6 Switching from Other Antipsychotics
`There are no systematically collected data to specifically address switching patients from other
`antipsychotics to RISPERDAL CONSTA®, or concerning concomitant administration with other
`antipsychotics. Previous antipsychotics should be continued for 3 weeks after the first injection
`of RISPERDAL CONSTA® to ensure that therapeutic concentrations are maintained until the
`main release phase of risperidone from the injection site has begun [see Clinical Pharmacology
`(12.3)]. For patients who have never taken oral RISPERDAL®, it is recommended to establish
`tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®.
`As recommended with other antipsychotic medications, the need for continuing existing EPS
`medication should be re-evaluated periodically.
`
`2.7 Co-Administration of RISPERDAL CONSTA® with Certain Other
`Medications
`Co-administration of carbamazepine and other CYP 3A4 enzyme inducers (e.g., phenytoin,
`rifampin, phenobarbital) with risperidone would be expected to cause decreases in the plasma
`concentrations of the sum of risperidone and 9-hydroxyrisperidone combined, which could lead
`to decreased efficacy of RISPERDAL CONSTA® treatment. The dose of risperidone needs to be
`titrated accordingly for patients receiving these enzyme inducers, especially during initiation or
`discontinuation of therapy with these inducers [see Drug Interactions (7.11)]. At the initiation of
`therapy with carbamazepine or other known CYP 3A4 hepatic enzyme inducers, patients should
`be closely monitored during the first 4-8 weeks, since the dose of RISPERDAL CONSTA® may
`need to be adjusted. A dose increase, or additional oral RISPERDAL®, may need to be
`considered. On discontinuation of carbamazepine or other CYP 3A4 hepatic enzyme inducers,
`the dosage of RISPERDAL CONSTA® should be re-evaluated and, if necessary, decreased.
`Patients may be placed on a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before
`the planned discontinuation of carbamazepine or other CYP 3A4 inducers to adjust for the
`expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone. For
`patients treated with the recommended dose of 25 mg RISPERDAL CONSTA® and
`discontinuing from carbamazepine or other CYP3A4 enzyme inducers, it is recommended to
`continue treatment with the 25-mg dose unless clinical judgment necessitates lowering the
`RISPERDAL CONSTA® dose to 12.5 mg or necessitates interruption of RISPERDAL
`CONSTA® treatment. The efficacy of the 12.5 mg dose has not been investigated in clinical
`trials.
`
`Reference ID: 4060013
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`

`
`
`Fluoxetine and paroxetine, CYP 2D6 inhibitors, have been shown to increase the plasma
`concentration of risperidone 2.5-2.8 fold and 3-9 fold respectively. Fluoxetine did not affect the
`plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of
`9-hydroxyrisperidone by about 10%. The dose of risperidone needs to be titrated accordingly
`when fluoxetine or paroxetine is co-administered. When either concomitant fluoxetine or
`paroxetine is initiated or discontinued, the physician should re-evaluate the dose of RISPERDAL
`CONSTA®. When initiation of fluoxetine or paroxetine is considered, patients may be placed on
`a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before the planned start of
`fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of
`risperidone. When fluoxetine or paroxetine is initiated in patients receiving the recommended
`dose of 25 mg RISPERDAL CONSTA®, it is recommended to continue treatment with the
`25 mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA® dose to
`12.5 mg or necessitates interruption of RISPERDAL CONSTA® treatment. When RISPERDAL
`CONSTA® is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of
`12.5 mg can be considered. The efficacy of the 12.5 mg dose has not been investigated in clinical
`trials. The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the
`pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied. [see Drug
`Interactions (7.11)]
`
`Instructions for Use
`2.8
`For deltoid or gluteal intramuscular injection only
`
`IMPORTANT RESOURCES
`For additional information, visit www.risperdalconsta.com or call Janssen Pharmaceuticals, Inc.
`at 1-800-JANSSEN (1-800-526-7736).
`
`Important Information
`
`RISPERDAL CONSTA® requires close attention to these step-by-step Instructions for Use to
`help ensure successful administration.
`Use components provided
`The components in this dose pack are specifically designed for use with RISPERDAL
`CONSTA®. RISPERDAL CONSTA® must be reconstituted only in the diluent supplied in the
`dose pack.
`Do not substitute ANY components of the dose pack.
`Do not store suspension after reconstitution
`Administer dose as soon as possible after reconstitution to avoid settling.
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`Reference ID: 4060013
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`
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`Proper dosing
`The entire contents of the vial must be administered to ensure intended dose of RISPERDAL
`CONSTA® is delivered.
`
`
`
`
`SINGLE-USE DEVICE
`Do not reuse. Medical devices require specific material characteristics to perform as intended.
`These characteristics have been verified for single use only. Any attempt to re-process the device
`for subsequent re-use may adversely affect the integrity of the device or lead to deterioration in
`performance.
`
`Dose pack contents
`
`
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`Reference ID: 4060013
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`
`
`
` Assemble components
`
`
`Step 1
`
`Take out dose pack Connect vial adapter to vial
`
`
`Wait 30 minutes
`Remove dose pack
`from the refrigerator
`and allow to sit at
`room temperature for
`at least 30 minutes
`before reconstituting.
`
`Do not warm any
`other way.
`
`
`Remove cap from
`vial
`Flip off colored cap
`from vial.
`
`Wipe top of the grey
`stopper with an
`alcohol swab. Allow
`to air dry.
`
`Do not remove grey
`rubber stopper.
`
`
`Prepare vial
`adapter
`Hold sterile blister as
`shown. Peel back and
`remove paper
`backing.
`
`Do not remove vial
`adapter from blister.
`
`Do not touch spike
`tip at any time. This
`will result in
`contamination.
`
`
`
`
`Connect vial adapter to
`vial
`Place vial on a hard
`surface and hold by the
`base. Center vial adapter
`over the grey rubber
`stopper. Push vial
`adapter straight down
`onto vial top until it
`snaps securely into place.
`
`Do not place vial adapter
`on at an angle or diluent
`may leak upon transfer to
`the vial.
`
`
`
`
`
`
`Reference ID: 4060013
`
` 10
`
`

`

`
`
`Connect prefilled syringe to vial adapter
`
`
`
`
`Use proper grip
`Hold by white collar
`at the tip of the
`syringe.
`
`Do not hold syringe
`by the glass barrel
`during assembly.
`
`
`
`
`Remove cap
`Holding the white
`collar, snap off the
`white cap.
`Do not twist or cut off
`the white cap.
`Do not touch syringe
`tip. This will result in
`contamination.
`
`
`
`
`
`The broken-off cap
`can be discarded.
`
`
`
`
`Connect syringe to
`vial adapter
`Hold vial adapter by
`skirt to keep
`stationary.
`Hold syringe by
`white collar then
`insert tip into the luer
`opening of the vial
`adapter.
`Do not hold the glass
`syringe barrel. This
`may cause the white
`collar to loosen or
`detach.
`Attach the syringe to
`the vial adapter with a
`firm clockwise
`twisting motion until
`it feels snug.
`Do not over-tighten.
`Over-tightening may
`cause the syringe tip
`to break.
`
`
`
`
`Remove sterile
`blister
`
`
`
`
`Keep vial vertical to
`prevent leakage.
`Hold base of vial and
`pull up on the sterile
`blister to remove.
`
`Do not shake.
`
`Do not touch exposed
`luer opening on vial
`adapter.
`This will result in
`contamination.
`
`
`
`
`Reference ID: 4060013
`
` 11
`
`

`

`
`
`
`Step 2
`
`
`
`Reconstitute microspheres
`
`
`
`
`
`Transfer suspension
`to syringe
`Invert vial
`completely. Slowly
`pull plunger rod down
`to withdraw entire
`contents from the vial
`into the syringe.
`
`
`
`
`Remove vial
`adapter
`Hold white collar on
`the syringe and
`unscrew from vial
`adapter.
`Tear section of the
`vial label at the
`perforation. Apply
`detached label to the
`syringe for
`identification
`purposes.
`Discard both vial and
`vial adapter
`appropriately.
`
`
`
`Suspend microspheres
`in diluent
`Continuing to hold
`down the plunger rod,
`shake vigorously for
`at least 10 seconds, as
`shown.
`Check the suspension.
`When properly mixed,
`the suspension appears
`uniform, thick and
`milky in color.
`Microspheres will be
`visible in the liquid.
`Immediately proceed
`to the next step so
`suspension does not
`settle.
`
`
`
`Inject diluent
`Inject entire amount
`of diluent from
`syringe into the vial.
`
`
`
`
`
`Reference ID: 4060013
`
` 12
`
`

`

`
`
`
`Step 3
`
`
`
`Attach needle
`
`Select appropriate needle
`Choose needle based on
`injection location
`(gluteal or deltoid).
`
`
`
`Resuspend microspheres
`Fully remove the blister
`pouch.
`Just before injection, shake
`syringe vigorously again, as
`some settling will have
`occurred.
`
`
`
`
`Attach needle
`Peel blister pouch open part
`way and use to grasp the base
`of the needle, as shown.
`Holding the white collar on
`the syringe, attach syringe to
`needle luer connection with a
`firm clockwise twisting
`motion until snug.
`Do not touch needle luer
`opening. This will result in
`contamination.
`
`Reference ID: 4060013
`
` 13
`
`

`

`
`
`
`Step 4
`
`
`Inject dose
`
`
`
`Remove air
`bubbles
`Hold needle
`upright and tap
`gently to make
`any air bubbles
`rise to the top.
`Slowly and
`carefully press
`plunger rod
`upward to
`remove air.
`
`Remove
`transparent
`needle protector
`Move the needle
`safety device
`back towards the
`syringe,
`as shown. Then
`hold white collar
`on syringe and
`carefully pull the
`transparent
`needle protector
`straight off.
`Do not twist
`transparent
`needle protector,
`as the luer
`connection may
`loosen.
`
`
`
`
`
`Inject
`Immediately
`inject entire
`contents of
`syringe
`intramuscularly
`(IM) into the
`gluteal or deltoid
`muscle of the
`patient.
`Gluteal injection
`should be made
`into the upper-
`outer quadrant of
`the gluteal area.
`Do not
`administer
`intravenously.
`
`
`
`
`Reference ID: 4060013
`
` 14
`
`
`
`
`
`Properly
`dispose of
`needles
`Check to
`confirm needle
`safety device is
`fully engaged.
`Discard in an
`approved sharps
`container.
`Also discard the
`unused needle
`provided in the
`dose pack.
`
`
`Secure needle in
`safety device
`Using one hand,
`place needle
`safety device at a
`45-degree angle
`on a hard, flat
`surface. Press
`down with a
`firm, quick
`motion until
`needle is fully
`engaged in safety
`device.
`
`Avoid needle
`stick injury:
`Do not use two
`hands.
`Do not
`intentionally
`disengage or
`mishandle the
`needle safety
`device.
`Do not attempt
`to straighten the
`needle or engage
`the safety device
`if the needle is
`bent or damaged.
`
`
`

`

`
`
`3 DOSAGE FORMS AND STRENGTHS
`RISPERDAL CONSTA® is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, and
`50 mg risperidone. It is provided as a dose pack, consisting of a vial containing the risperidone
`microspheres, a pre-filled syringe containing 2 mL of diluent for RISPERDAL CONSTA®, a
`West-Medimop Vial Adapter®, and two Terumo SurGuard® 3 Needles for intramuscular
`injection (a 21 G UTW 1-inch needle with needle protection device for deltoid administration
`and a 20 G TW 2-inch needle with needle protection device for gluteal administration).
`
`4 CONTRAINDICATIONS
`RISPERDAL CONSTA® is contraindicated in patients with a known hypersensitivity to either
`risperidone or paliperidone, or to any of the excipients in the RISPERDAL CONSTA®
`formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have
`been reported in patients treated with risperidone and in patients treated with paliperidone.
`Paliperidone 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. RISPERDAL CONSTA® (risperidone) is not approved for the
`treatment of dementia-related psychosis (see Boxed Warning).
`
`5.2 Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients
`with Dementia-Related Psychosis
`Cerebrovascular adverse