IMPORTANT SAFETY INFORMATION FOR INVEGA^® SUSTENNA^®, RISPERDAL^® CONSTA^®, INVEGA^®, AND CONCERTA^®

IMPORTANT SAFETY INFORMATION FOR INVEGA^® SUSTENNA^® (paliperidone palmitate)

• Contraindications: Paliperidone is contraindicated in patients with a known hypersensitivity to either paliperidone, risperidone, or to any components of 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^® 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 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. 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.
• 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 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.
• 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.
• 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.

IMPORTANT SAFETY INFORMATION FOR RISPERDAL^® CONSTA^® (risperidone)

• Contraindications: RISPERDAL^® CONSTA^® is contraindicated in patients with a known hypersensitivity to the product.
• 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. The incidence of CAEs 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. 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.
• 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. 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, some cases extreme and associated with ketoacidosis, hyperosmolar coma or death have 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 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. Monitor glucose regularly in patients with diabetes or at risk for diabetes. Some patients require continuation of anti-diabetic 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.
• Hyperprolactinemia: As with other drugs that antagonize dopamine D₂ receptors, risperidone 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 and Syncope: RISPERDAL^® CONSTA^® may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. RISPERDAL^® CONSTA^® 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) and additionally elderly patients with renal or hepatic impairment. Monitoring should be considered in patients for whom this may be of concern.
• Leukopenia, Neutropenia and Agranulocytosis have been reported with antipsychotics, including RISPERDAL^® CONSTA^®. 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 RISPERDAL^® CONSTA^® 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 RISPERDAL^® CONSTA^® and have their WBC followed until recovery.
• Potential for Cognitive and Motor Impairment: Somnolence was reported in multiple trials in subjects treated with RISPERDAL^® CONSTA^®. Since 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 adversely affect them.
• Seizures: RISPERDAL^® CONSTA^® should be used cautiously in patients with a history of seizures.
• Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer’s dementia. 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: For intramuscular injection only. 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).
• 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 disorder were weight increased (5% in monotherapy trial) and tremor and Parkinsonism (≥10% in adjunctive therapy trial).

Please see the full Prescribing Information.

IMPORTANT SAFETY INFORMATION FOR INVEGA^® (paliperidone)

• 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 (eg, 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 (eg, heart failure, history of MI or ischemia, conduction abnormalities), cerebrovascular disease or conditions that would predispose patients to hypotension (eg, 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.

Please see the full Prescribing Information.

IMPORTANT SAFETY INFORMATION FOR CONCERTA^® (methylphenidate HCl)

CONCERTA^® should not be taken by patients with: allergies to methylphenidate or other ingredients in CONCERTA^®; significant anxiety, tension, or agitation; glaucoma; Tourette's syndrome, tics, or family history of Tourette's syndrome; current or recent use of monoamine oxidase inhibitors (MAOIs). Children under 6 years of age should not take CONCERTA^®.

Abuse of methylphenidate may lead to dependence. CONCERTA^® should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, other serious cardiac problems, or patients with pre-existing severe gastrointestinal narrowing. Use with caution in patients with hypertension and other cardiovascular conditions, psychosis, bipolar disorder, and history of seizures/EEG abnormalities. Stimulants may cause new psychotic or manic symptoms; discontinuation of treatment may be appropriate. Aggressive behavior or hostility should be monitored in patients beginning ADHD treatment. Methylphenidate may produce difficulties with visual accommodation and blurring of vision. Hematologic monitoring is advised during prolonged therapy. Growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

The most common adverse reaction (>5%) reported in children and adolescents was upper abdominal pain. The most common adverse reactions (>10%) reported in adults were dry mouth, nausea, decreased appetite, headache, and insomnia.

Please see full US Prescribing Information.