Titusville, NJ (September 26, 2012) – Janssen Pharmaceuticals, Inc., announced today that the U.S. Food and Drug Administration (FDA) has approved the Supplemental New Drug Application (sNDA) for updated product labeling for INVEGA® SUSTENNA® (paliperidone palmitate). INVEGA® SUSTENNA® is a monthly extended-release injectable suspension atypical antipsychotic indicated for the treatment of schizophrenia. Among other changes, the approved labeling provides greater flexibility and dosing options for healthcare providers.
After the first initiation dose of INVEGA® SUSTENNA®, patients are given a second initiation dose one week later. Maintenance doses are then given once monthly. The updated product label includes additional instructions for appropriate alternatives to help avoid a missed dose when a patient cannot receive the second dose of INVEGA® SUSTENNA® when recommended.
- To avoid a missed dose, patients may now be given the second initiation dose four days before or after the one-week time point, instead of two days before or after the one-week time point as included in the original label.
- Additionally, if the second INVEGA® SUSTENNA® initiation injection is completely missed, the recommended re-initiation depends on the length of time that has elapsed since the patient's first injection.
Additional Prescribing Information revisions were also made to the Warnings and Precautions section. Dosage adjustment instructions have been added for when INVEGA® SUSTENNA® is co-administered with a strong CYP3A4 inducer (e.g., carbamazepine, rifampin or St. John’s wort). Additionally, information about the product’s Use in Specific Populations, notably nursing women, persons with Parkinson’s Disease or Lewy Body Dementia; and updates to the Boxed Warning and Indications and Usage have also been added. The revised label can be viewed in its entirety at http://www.InvegaSustenna.com/important-product-information.
Approved in 2009, INVEGA® SUSTENNA® is the first injectable once-monthly atypical antipsychotic medication indicated for the treatment of schizophrenia in the U.S. Efficacy was established in four short-term studies and one longer-term study in adults. INVEGA® SUSTENNA® is proven to treat symptoms of schizophrenia and can also be used to lessen the chance of schizophrenia symptoms coming back over the longer-term. INVEGA® SUSTENNA® is administered by a healthcare professional once a month after starting doses. Visit www.InvegaSustenna.com for full prescribing information.
About Schizophrenia and its Treatment
Schizophrenia is a complex brain disorder that affects 2.5 million American adults. The disease typically manifests as hallucinations, delusions, and disorganized thoughts and behavior. Because there are currently no physical or lab tests that diagnose this condition, schizophrenia is diagnosed by the presence of symptom types. Researchers have identified various risk factors for this disease, including heredity, brain damage, and environmental factors, such as social stress, isolation, and drug use. The full constellation of symptoms and the relevant diagnostic criteria should be consulted and are available in the current Diagnostic and Statistical Manual of Mental Disorders as applicable.
Approximately 80 percent of patients with schizophrenia experience at least one relapse within five years of diagnosis, and the risk for relapse in patients can substantially increase as a result of non-adherence. While no medication can assure that patients will be adherent or that patient adherence will improve, the use of a long-acting antipsychotic injectable medication can allow for health care professionals to identify if a patient misses a dose and intervene.
About Janssen Pharmaceuticals, Inc.
As a member of the Janssen Pharmaceutical Companies, Janssen Pharmaceuticals, Inc. is dedicated to addressing and solving some of the most important unmet medical needs of our time. Driven by our commitment to patients, we work together to bring innovative ideas, products, services and solutions to individuals with serious conditions, and to physicians throughout the world.
INVEGA® SUSTENNA® (paliperidone palmitate) is indicated for the treatment of schizophrenia. Efficacy was established in four short-term studies and one longer-term study in adults.
IMPORTANT SAFETY INFORMATION FOR INVEGA® SUSTENNA® (paliperidone palmitate)
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.
- INVEGA® SUSTENNA® is not approved for the treatment of patients with dementia-related psychosis.
See full Prescribing Information for Warnings and Precautions (5.1).
Contraindications: Paliperidone is contraindicated in patients with a known hypersensitivity to either paliperidone, risperidone, or to any components of the formulation.
Cerebrovascular Adverse Reactions: Cerebrovascular Adverse Reactions (e.g., stroke, transient ischemic attacks), including fatalities, were reported in placebo-controlled trials in elderly patients with dementia-related psychosis taking oral risperidone, aripiprazole, and olanzapine. The incidence of Cerebrovascular Adverse Reactions 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 QTc interval and in patients with risk factors for prolonged QTc 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 torsades 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 female 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 (see full Prescribing Information). Discontinue drug if clinically appropriate. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.
- Hyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death have been reported in patients treated with all atypical antipsychotics (APS). Patients starting treatment with APS who have or are at risk for diabetes mellitus should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia during treatment should also undergo fasting blood glucose testing. All patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia. Some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug.
- Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.
- Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Orthostatic Hypotension and Syncope: INVEGA® SUSTENNA® may induce orthostatic hypotension in some patients due to its alpha-blocking activity. INVEGA® SUSTENNA® should be used with caution in patients with known cardiovascular disease, cerebrovascular disease or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, treatment with antihypertensive medications). Monitoring should be considered in patients for whom this may be of concern.
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.
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.
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 performing activities that require mental alertness such as operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA® SUSTENNA® does not adversely affect them.
Seizures: INVEGA® SUSTENNA® should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold. Conditions that lower seizure threshold may be more prevalent in patients 65 years or older.
Administration: For intramuscular injection only. Care should be taken to avoid inadvertent injection into a blood vessel.
Drug Interactions: Strong CYP3A4 inducers: It may be necessary to increase the dose of INVEGA® SUSTENNA® when a CYP3A4 strong inducer (e.g. carbamazepine, rifampin, St. John’s wort) is added. It may be necessary to decrease the dose when a CYP3A4 strong inducer is discontinued.
Pregnancy/Nursing: Patients should be advised to notify their physician if they become pregnant/intend to become pregnant or intend to nurse during treatment with
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.