For Billing Reimbursement and SupportImportant Safety Information for INVEGA® SUSTENNA®Important Safety Information RISPERDAL® CONSTA®

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INVEGA® SUSTENNA® (paliperidone palmitate) extended-release injectable suspension and
RISPERDAL® CONSTA® (risperidone) long-acting injection

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Introduction:
This Web site is intended for informational purposes and is not intended to provide reimbursement or legal advice. It is not intended to increase or maximize reimbursement by any payer. We strongly suggest that you consult your payer organization with regard to local reimbursement policies. The information presented represents no statement, promise, or guarantee by Janssen®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. concerning levels of reimbursement, payment, or charge. Laws, regulations, and policies concerning reimbursement are complex and are updated frequently and should be verified by the user. Please consult your legal counsel or reimbursement specialist for any reimbursement or billing questions.

INVEGA® SUSTENNA® (paliperidone palmitate) extended-release injectable suspension is indicated for the acute and maintenance treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION FOR INVEGA® SUSTENNA®

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 the 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. INVEGA® SUSTENNA® (paliperidone palmitate) is not approved for the treatment of patients with dementia-related psychosis.

  • Hypersensitivity: Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone and paliperidone, which is a metabolite of risperidone. Therefore paliperidone is contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in INVEGA® SUSTENNA®.

  • Cerebrovascular Adverse Events (CAEs): CAEs, including fatalities and stroke, have been reported in elderly patients with dementia-related psychosis taking oral risperidone in clinical trials. The incidence of CAEs with risperidone was significantly higher than with placebo. INVEGA® SUSTENNA® is not approved for the treatment of patients with dementia-related psychosis.

  • Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with the use of antipsychotic medications, including paliperidone. Clinical manifestations include muscle rigidity, fever, altered mental status and evidence of autonomic instability (see full Prescribing Information). Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and close medical monitoring, and treatment of any concomitant serious medical problems.

  • QT Prolongation: Paliperidone causes a modest increase in the corrected QT (QTc) interval. Avoid the use of drugs that also increase QT interval and in patients with risk factors for prolonged QT interval. Paliperidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Certain circumstances may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.

  • Tardive Dyskinesia (TD): TD is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic medications. The risk of developing TD and the likelihood that dyskinetic movements will become irreversible are believed to increase with duration of treatment and total cumulative dose, but can develop after relatively brief treatment at low doses. Elderly women patients appeared to be at increased risk for TD, although it is impossible to predict which patients will develop the syndrome. Prescribing should be consistent with the need to minimize the risk of TD. Discontinue drug if clinically appropriate. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

  • Hyperglycemia and Diabetes: Hyperglycemia, some cases extreme and associated with ketoacidosis, hyperosmolar coma or death has been reported in patients treated with atypical antipsychotics (APS), including INVEGA® SUSTENNA®. Patients starting treatment with APS who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. Some patients require continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

  • Weight Gain: Weight gain has been observed with INVEGA® SUSTENNA® and other atypical antipsychotic medications. Monitor weight gain.

  • Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, INVEGA® SUSTENNA® elevates prolactin levels and the elevation persists during chronic administration. Paliperidone has a prolactin-elevating effect similar to risperidone, which is associated with higher levels of prolactin elevation than other antipsychotic agents.

  • Orthostatic Hypotension and Syncope: INVEGA® SUSTENNA® may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. Monitoring should be considered in patients for whom this may be of concern. INVEGA® SUSTENNA® should be used with caution in patients with known cardiovascular disease, cerebrovascular disease or conditions that would predispose patients to hypotension.

  • Leukopenia, Neutropenia and Agranulocytosis have been reported with antipsychotics, including paliperidone. Patients with a history of clinically significant low white blood cell count (WBC) or drug-induced leukopenia/neutropenia should have frequent complete blood cell counts during the first few months of therapy. At the first sign of a clinically significant decline in WBC and in the absence of other causative factors, discontinuation of INVEGA® SUSTENNA® should be considered. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue INVEGA® SUSTENNA® and have their WBC followed until recovery.

  • Potential for Cognitive and Motor Impairment: Somnolence, sedation, and dizziness were reported as adverse reactions in subjects treated with INVEGA® SUSTENNA®. INVEGA® SUSTENNA® has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA® SUSTENNA® does not affect them adversely, and should use caution when operating machinery.

  • Seizures: INVEGA® SUSTENNA® should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold.

  • Suicide: The possibility of suicide attempt is inherent in schizophrenia. Close supervision of high-risk patients should accompany drug therapy.

  • Administration: For intramuscular injection only. Care should be taken to avoid inadvertent injection into a blood vessel.

  • Commonly Observed Adverse Reactions for INVEGA® SUSTENNA®: The most common adverse reactions in clinical trials in patients with schizophrenia(≥5% and twice placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal disorder.


Please see the full Prescribing Information.


RISPERDAL® CONSTA®. (risperidone) long-acting injection is indicated for the treatment of schizophrenia and the maintenance treatment of Bipolar I Disorder, either as monotherapy or as adjunctive therapy to lithium or valproate.

IMPORTANT SAFETY INFORMATION FOR RISPERDAL® CONSTA®.

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 the 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.

Cerebrovascular Adverse Events (CAEs): CAEs, including fatalities, have been reported in elderly patients with dementia-related psychosis taking oral risperidone in clinical trials. The incidence of CAEs with risperidone was significantly higher than with placebo. RISPERDAL® CONSTA®. is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with the use of antipsychotic medications, including RISPERDAL® CONSTA®. . Clinical manifestations include muscle rigidity, fever, altered mental status and evidence of autonomic instability (see full Prescribing Information). Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems.

Tardive Dyskinesia (TD): TD is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic medications. The risk of developing TD and the likelihood that dyskinetic movements will become irreversible are believed to increase with duration of treatment and total cumulative dose. Elderly patients appeared to be at increased risk for TD. Prescribing should be consistent with the need to minimize the risk of TD. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Hyperglycemia and Diabetes: Hyperglycemia, some cases extreme and associated with ketoacidosis, hyperosmolar coma or death has been reported in patients treated with atypical antipsychotics (APS), including RISPERDAL® CONSTA®. . Patients starting treatment with APS who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, RISPERDAL® CONSTA® elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.

Orthostatic Hypotension: RISPERDAL® CONSTA®. may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. Monitoring should be considered in patients for whom this may be of concern. RISPERDAL® CONSTA®. should be used with caution in patients with known cardiovascular disease, and conditions that would predispose patients to hypotension.

Leukopenia, Neutropenia and Agranulocytosis has been reported with antipsychotics, including risperidone. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have frequent complete blood cell counts during the first few months of therapy. At the first sign of a decline in WBC and in the absence of other causative factors, discontinuation of RISPERDAL® CONSTA®. should be considered.

Potential for Cognitive and Motor Impairment: RISPERDAL® CONSTA®. has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that RISPERDAL® CONSTA® does not affect them adversely.

Seizures: RISPERDAL® CONSTA®. should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold.

Dysphagia: Esophageal dysmotility and aspiration can occur. Use cautiously in patients at risk for aspiration pneumonia.

Priapism has been reported. Severe priapism may require surgical intervention.

Thrombotic Thrombocytopenic Purpura (TTP) has been reported.

Administration: Care should be taken to avoid inadvertent injection into a blood vessel.

Suicide: The possibility of suicide attempt is inherent in schizophrenia or bipolar disorder. Close supervision of high-risk patients should accompany drug therapy.

Increased sensitivity in patients with Parkinson's disease or those with dementia with Lewy bodies has been reported. Manifestations and features are consistent with NMS.

Use RISPERDAL® CONSTA®. with caution in patients with conditions and medical conditions that could affect metabolism or hemodynamic responses (e.g. recent myocardial infarction or unstable cardiac disease).

Extrapyramidal Symptoms (EPS): The overall incidence of EPS-related adverse events in patients with schizophrenia treated with 25 mg and 50 mg of RISPERDAL® CONSTA®. and placebo, respectively, were akathisia* (4%, 11%, 6%), Parkinsonism† (8%, 15%, 9%) and tremor (0%, 3%, 0%).

* Akathisia and restlessness
† Extrapyramidal disorder, musculoskeletal stiffness, muscle rigidity, and bradykinesia

The overall incidence of EPS-related adverse events in patients with Bipolar I Disorder treated with adjunctive therapy with RISPERDAL® CONSTA® and placebo respectively were Parkinsonism** (15% and 6%), tremor (24% and 16%), and dyskinesia‡ (6% and 3%).

** Muscle rigidity, hypokinesia, cogwheel rigidity, and bradykinesia
‡ Muscle twisting and dyskinesia

Weight Gain: In a 12-week trial in patients with schizophrenia, the percentage of patients experiencing weight gain (>7% of baseline body weight) was 6% placebo vs 9% RISPERDAL® CONSTA®.

In a 24-month monotherapy trial in patients with Bipolar I Disorder, the percentage of patients experiencing weight gain (>7% of baseline body weight) was 2.8% placebo vs 11.6% RISPERDAL® CONSTA®.

In a 52-week adjunctive therapy trial in patients with Bipolar I Disorder, the percentage of patients experiencing weight gain (>7% of baseline body weight) was 27.3% placebo vs 26.8% RISPERDAL® CONSTA®.

Maintenance Treatment: Patients should be periodically reassessed to determine the need for continued treatment.

Commonly Observed Adverse Reactions for RISPERDAL® CONSTA®. : The most common adverse reactions in clinical trials in patients with schizophrenia (≥5%) were headache, Parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increase, pain in extremities, and dry mouth.

The most common adverse reactions in clinical trials in patients with Bipolar I Disorder were weight increased (5% in monotherapy trial) and tremor and Parkinsonism (≥ 10% in adjunctive therapy trial).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

01CS09051


For more information, read the full US Prescribing Information by clicking here.