Titusville, N.J., April 11, 2011 - The U.S. Food and Drug Administration (FDA) on April 6 approved INVEGA® (paliperidone) extended-release tablets for the treatment of schizophrenia in adolescents 12 to 17 years of age. The efficacy of INVEGA® to treat schizophrenia in adolescents was established in one six-week clinical study. INVEGA® is an atypical antipsychotic medication and was first approved in the U.S. in December 2006 for the treatment of schizophrenia in adults. Janssen Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., markets INVEGA® in the U.S.
Schizophrenia is a complex, chronic brain disorder that causes a variety of symptoms which can include hearing voices, having fixed false beliefs or delusions, disorganized thinking, and unusual behaviors. It can begin in late adolescence or early adulthood, and about one percent of adults in the general population has schizophrenia. The prevalence of schizophrenia in adolescents is not known, but it is estimated to be less than in the adult population.
"Although rare, schizophrenia in adolescents is a very serious and disabling brain condition that affects every aspect of an adolescent's life and has significant consequences," said Husseini Manji, M.D., F.R.C.P.C., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Pharmaceutical Research & Development, LLC. "This new indication for INVEGA® provides an additional option for clinicians who treat adolescents with schizophrenia and further demonstrates our commitment to helping people with diseases of the brain."
Early diagnosis of schizophrenia and medical treatment are important in managing this life-long disease. Schizophrenia can be successfully treated over time but, like many treatable chronic diseases, there is no known cure. Adolescents with schizophrenia are usually treated with a comprehensive plan, including medication, individual therapy and specialized programs. Medication requires careful monitoring by a skilled clinician.
The efficacy of INVEGA® in adolescents with schizophrenia was established in a six-week randomized, double-blind, placebo-controlled study using a fixed-dose weight-based treatment group design over a dose range of 1.5 to 12 milligrams per day. The study was conducted in several countries, including the United States, and involved adolescents ranging in age from 12 years to 17 years, all of whom met DSM-IV criteria for schizophrenia, with diagnosis confirmation using a specialized diagnostic assessment for affective disorders and schizophrenia.
Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS), a validated multi-item inventory composed of 30 individual items to evaluate positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression.
Overall, this study demonstrated efficacy of INVEGA® in adolescents with the dose range of 3 to 12 milligrams a day. The study used a weight-based dosing regimen with a low, medium, and high dose groups. INVEGA® was adequately tolerated within the dose range of 3 to 12 milligrams a day. Adverse events were dose related. In the total paliperidone treatment group the most commonly reported adverse events in this study were: somnolence (sleepiness) (13%), akathisia (restlessness) (9%), headache (9%), and insomnia (9%).
Please see the Important Safety Information below. Please visit http://janssen.com/products.html for additional important product information.
IMPORTANT SAFETY INFORMATION FOR INVEGA® (paliperidone)
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® is not approved for the treatment of patients with dementia-related psychosis.
Contraindications: Paliperidone is contraindicated in patients with a known hypersensitivity to either paliperidone, risperidone, or to any of the components in the formulation.
Cerebrovascular Adverse Events (CAEs): CAEs (e.g., stroke, transient ischemia 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 CAEs was significantly higher than with placebo. INVEGA® 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 (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. The 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- Hyperglycemia, some cases extreme and associated with ketoacidosis, hyperosmolar coma or death has been reported in patients treated with atypical antipsychotics (APS), including INVEGA®. 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 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 anti-diabetic treatment despite discontinuation of the suspect drug.
Dyslipidemia-Undesirable alterations in lipids 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. When treating adolescent patients with INVEGA®, weight gain should be assessed against that expected with normal growth.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, INVEGA® 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.
Gastrointestinal: INVEGA® should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing. Rare instances of obstructive symptoms have been reported in patients with known strictures taking non-deformable formulations. INVEGA® should only be used in patients who are able to swallow the tablet whole.
Orthostatic Hypotension and Syncope: INVEGA® may induce orthostatic hypotension in some patients due to its alpha-blocking activity. INVEGA® should be used with caution in patients with known cardiovascular disease (e.g., heart failure, history of MI or ischemia, conduction abnormalities), cerebrovascular disease or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, treatment with anti-hypertensive medications). Monitoring should be considered in patients who are vulnerable 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® 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® and have their WBC followed until recovery.
Potential for Cognitive and Motor Impairment: Somnolence was reported in subjects treated with INVEGA®. INVEGA® 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® does not adversely affect them.
Seizures: INVEGA® 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.
Suicide: The possibility of suicide attempt is inherent in psychotic illnesses. Close supervision of high-risk patients should accompany drug therapy. Prescriptions should be written for the smallest quantity of tablets to reduce the risk of overdose.
Commonly Observed Adverse Reactions: The most commonly observed adverse reactions in clinical trials occurring at an incidence of >5% and at least 2 times placebo in the treatment of schizophrenia were: Adults - extrapyramidal symptoms, tachycardia, and akathisia; Adolescents (12-17 years of age) were: somnolence, akathisia, tremor, dystonia, cogwheel rigidity, anxiety, weight increased and tachycardia. The most commonly observed adverse reactions in clinical trials occurring at an incidence of ?5% and at least 2 times placebo in the treatment of schizoaffective disorder were: Adults - extrapyramidal symptoms, somnolence, dyspepsia, constipation, weight increased, and nasopharyngitis.
This is not a complete list of all possible side effects. Ask your doctor or treatment team if you have any questions or want more information.
If you have any questions about INVEGA® or your therapy, talk with your doctor.
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.
INVEGA® (paliperidone) extended release tablets, an atypical antipsychotic medication, was approved in the U.S. in December 2006. Janssen Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., markets INVEGA®. It is approved for the treatment of schizophrenia in adults and adolescents (12-17 years of age) in the U.S. The efficacy of INVEGA® in schizophrenia was established in three six-week clinical trials in adults and in one six-week trial in adolescents (12-17 years of age), as well as in one maintenance trial in adults. INVEGA® is the only medication approved to treat schizoaffective disorder in adults. The efficacy of INVEGA® in schizoaffective disorder was established in two six-week trials in adults.
About Johnson & Johnson Pharmaceutical Research & Development
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) is a subsidiary of Johnson & Johnson, the world's most broadly based producer of health care products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout the United States, Europe and Asia. J&JPRD is focusing its drug discovery and drug development efforts to address unmet medical needs worldwide in a variety of therapeutic areas including cardiovascular and metabolic diseases, oncology, immunology, central nervous system disorders, including pain, and virology. More information can be found at http://www.jnjpharmarnd.com.
Janssen Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., is based in Titusville, N.J., and is the only large pharmaceutical company in the U.S. dedicated solely to mental health. It currently markets prescription medications for the treatment of schizophrenia, bipolar mania, schizoaffective disorder and the treatment of symptoms associated with autistic disorder. Ortho-McNeil-Janssen Pharmaceuticals, Inc, is a member of the Johnson & Johnson family of companies. For more information about Janssen, visit http://www.janssen.com.