U.S. Products Using Alkermes Technologies

All product information provided is intended for the U.S. audience only. These products may not be available in countries outside the U.S. or may be available under a different trademark; in different strengths; or for different indications. Countries outside the U.S. may have different regulatory requirements that would call for different information to be available.

Products using Alkermes technologies:

We have granted licenses under our proprietary technologies to enable third parties to develop, commercialize and, in some cases, manufacture products for which we receive royalties and/or manufacturing revenues. Such arrangements in the U.S. include the following:

Bydureon Prescribing Information Product Website

Important Safety Information for BYDUREON® (exenatide extended-release for injectable suspension)

WARNING: RISK OF THYROID C-CELL TUMORS

Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies. BYDUREON is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with BYDUREON. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

See full prescribing information for complete boxed warning.

 

Indications

BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.

  • Because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans, prescribe only to patients for whom potential benefits are considered to outweigh potential risk.
  • Not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.
  • Not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis, and cannot be recommended for use with insulin.
  • BYDUREON and BYETTA® (exenatide) injection both contain the same active ingredient, exenatide, and should not be used together.
  • Exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, based on postmarketing data. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON; consider other antidiabetic therapies for these patients.

Contraindications

  • BYDUREON is contraindicated in patients with known prior severe hypersensitivity reactions to exenatide or to any of the product components.

Warnings and Precautions

  • Based on postmarketing data, exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation of BYDUREON, observe patients carefully for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYDUREON should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
  • Increased risk of hypoglycemia when used in combination with glucose-independent insulin secretagogues (eg, sulfonylureas). Clinicians may consider reducing the sulfonylurea (SFU) dose.
  • Should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or moderate renal failure. Postmarketing reports of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation.
  • Not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
  • Patients may develop antibodies to exenatide. In 5 registration trials, attenuated glycemic response was associated in 6% of BYDUREON-treated patients with antibody formation. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
  • Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and other suspect medications and promptly seek medical advice.
  • No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYDUREON or any other antidiabetic drug.

Withdrawals

  • In 5 comparator-controlled, 24- to 30-week BYDUREON trials, the incidence of withdrawal due to adverse events was 4.9% for BYDUREON, 4.9% for BYETTA, and 2.0% for other comparators. The most common adverse reactions leading to withdrawal for BYDUREON, BYETTA, and comparators respectively were: nausea (0.5%,1.5%, 0.3%); injection-site nodule (0.5%, 0.0%, 0.0%); diarrhea (0.3%, 0.4%, 0.3%); injection-site reaction (0.2%, 0.0%, 0.0%); and headache (0.2%, 0.0%, 0.0%). One percent of BYDUREON patients withdrew due to injection-site adverse reactions.

Adverse Reactions (≥5%)

  • BYDUREON vs BYETTA: 24-week trial, nausea (14% vs 35%), diarrhea (9.3% vs 4.1%), injection-site erythema (5.4% vs 2.4%); 30-week trial, nausea (27% vs 33.8%), diarrhea (16.2% vs 12.4%), vomiting (10.8% vs 18.6%), injection-site pruritus (18.2% vs 1.4%), constipation (10.1% vs 6.2%), gastroenteritis viral (8.8% vs 5.5%), gastroesophageal reflux disease (7.4% vs 4.1%), dyspepsia (7.4% vs 2.1%), injection-site erythema (7.4% vs 0.0%), fatigue (6.1% vs 3.4%), headache (6.1% vs 4.8%), injection-site hematoma (5.4% vs 11.0%).
  • BYDUREON vs titrated insulin glargine: nausea (12.9% vs 1.3%), headache (9.9% vs 7.6%), diarrhea (9.4% vs 4.0%), injection-site nodule (6.0% vs 0.0%).
  • Combination trial vs sitagliptin and pioglitazone: nausea (24.4% vs 9.6% and 4.8%), diarrhea (20.0% vs 9.6% and 7.3%), vomiting (11.3% vs 2.4% and 3.0%), headache (9.4% vs 9.0% and 5.5%), constipation (6.3% vs 3.6% and 1.2%), fatigue (5.6% vs 0.6% and 3.0%), dyspepsia (5.0% vs 3.6% and 2.4%), decreased appetite (5.0% vs 1.2% and 0.0%), injection-site pruritus (5.0% vs 4.8% and 1.2%).
  • Monotherapy trial vs sitagliptin, pioglitazone, and metformin: nausea (11.3% vs 3.7%, 4.3%, and 6.9%), diarrhea (10.9% vs 5.5%, 3.7%, and 12.6%), injection-site nodule (10.5% vs 6.7%, 3.7%, and 10.2%), constipation (8.5% vs 2.5%, 1.8%, and 3.3%), headache (8.1% vs 9.2%, 8.0%, and 12.2%), dyspepsia (7.3% vs 1.8%, 4.9%, and 3.3%).
  • Injection-site reactions were observed more frequently in BYDUREON-treated patients (17.1%) vs patients treated with BYETTA (12.7%), titrated insulin glargine (1.8%), or placebo injection (6.4%-13.0%). Injection-site reactions were observed in 14.2% of antibody-positive patients vs 3.1% of antibody-negative patients, with higher incidence in those with higher-titer antibodies. BYETTA-treated patients had similar incidence between antibody-positive and antibody-negative patients (5.8% vs 7.0%). Small, asymptomatic, subcutaneous injection-site nodules are seen with the use of BYDUREON.

Hypoglycemia

  • No major hypoglycemia was reported for BYDUREON- or comparator-treated patients in five 24- to 30-week trials. Minor hypoglycemia incidences for BYDUREON vs comparator-treated patients were as follows: 24-week trial vs BYETTA: with SFU, 12.5% vs 11.8%; without SFU, 0.0% for both; 30-week trial vs BYETTA: with SFU, 14.5% vs 15.4%; without SFU, 0.0% vs 1.1%; monotherapy trial vs sitagliptin, pioglitazone, and metformin: 2.0% vs 0.0% (all comparators); combination trial vs sitagliptin and pioglitazone: 1.3% vs 3.0% and 1.2%; vs titrated insulin glargine, with SFU, 20.0% vs 43.9%; without SFU, 3.7% vs 19.1%.

Drug Interactions

  • BYDUREON slows gastric emptying and can reduce the rate of absorption of orally administered drugs. Use with caution with oral medications.
  • Postmarketing reports of increased international normalized ratio (INR) sometimes associated with bleeding with concomitant use of warfarin. Monitor INR frequently until stable upon initiation or alteration of BYDUREON.

Use in Specific Populations

  • Based on animal data, BYDUREON may cause fetal harm and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Caution should be exercised when administered to a nursing woman.
  • Use in pediatric patients is not recommended as safety and effectiveness have not been established.

For complete safety profile and other important prescribing considerations, see the Prescribing Information and Medication Guide.

RISPERDAL CONSTA® (risperidone Long-Acting Injection), a Janssen product, is indicated for the treatment of schizophrenia and for the longer-term treatment of Bipolar I Disorder and utilizes Alkermes’ proprietary extended-release microsphere technology.
Prescribing Information

Important Safety Information for RISPERDAL CONSTA® (risperidone Long-Acting Injection)

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® is not approved for use in patients with dementia-related psychosis.

  • 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/mm 3) 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.

INVEGA SUSTENNA® (paliperidone palmitate), a Janssen product, is indicated for the treatment of schizophrenia and schizoaffective disorder and utilizes Alkermes’ proprietary nanoparticle injectable extended-release technology.
Prescribing Information

Important Safety Information and Indication for INVEGA SUSTENNA® (paliperidone palmitate)

INVEGA SUSTENNA® (paliperidone palmitate) is indicated for schizophrenia and schizoaffective disorder.

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
  • INVEGA SUSTENNA® 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 excipients 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 by a healthcare professional. Care should be taken to avoid inadvertent injection into a blood vessel.
  • Drug Interactions: Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of INVEGA SUSTENNA ® when a strong inducer of both CYP3A4 and P-gp (e.g. carbamazepine, rifampin, St. John’s wort) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of INVEGA SUSTENNA ®.
  • 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 INVEGA SUSTENNA®.
  • 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. No adverse events occurred at a rate of ≥5% and twice placebo during the long-term double-blind, placebo-controlled study in patients with schizoaffective disorder. The following adverse reactions occurred more frequently (a ≥2% difference vs. placebo) in the long-term study in patients with schizoaffective disorder: weight increased, nasopharyngitis, headache, hyperprolactinemia, and pyrexia.

Please see the full Prescribing Information

INVEGA TRINZA®; (paliperidone palmitate), a Janssen product, is indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA for at least four months and utilizes Alkermes’ proprietary technology.
Prescribing Information

Important Safety Information and Indication for INVEGA TRINZA® (paliperidone palmitate)

INVEGA TRINZA® (paliperidone palmitate) a 3-month injection, is an atypical antipsychotic indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA® (1-month paliperidone palmitate) for at least four months.

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
  • INVEGA TRINZA® 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 excipients 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 TRINZA® 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 TRINZA® may induce orthostatic hypotension in some patients due to its alpha-blocking activity. INVEGA TRINZA® 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 TRINZA® 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 TRINZA® and have their WBC followed until recovery.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, INVEGA TRINZA® 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 TRINZA®. INVEGA TRINZA® 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 TRINZA® does not adversely affect them.

Seizures: INVEGA TRINZA® 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 by a healthcare professional. Care should be taken to avoid inadvertent injection into a blood vessel.

Drug Interactions: Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of INVEGA TRINZA®when a strong inducer of both CYP3A4 and P-gp (e.g. carbamazepine, rifampin, St. John’s wort) is co-administered. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended release tablets.

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 INVEGA TRINZA®.

Commonly Observed Adverse Reactions for INVEGA TRINZA®: The most common adverse reactions (incidence ≥ 5% and occurring at least twice as often as placebo) were injection site reaction, weight increased, headache, upper respiratory tract infection, akathisia and parkinsonism.

Please see full Prescribing Information , including Boxed WARNING, for INVEGA TRINZA®.

 

BYDUREON® is a registered trademark of Amylin Pharmaceuticals, LLC. AMPYRA® is a registered trademark of Acorda Therapeutics, Inc. RISPERDAL CONSTA®, INVEGA SUSTENNA® and INVEGA TRINZA® are trademarks of Johnson & Johnson.

This page is intended for the U.S. audience only.