SECUADO is indicated for the treatment of adults with schizophrenia [ see Clinical Studies (14) ]. SECUADO is an atypical antipsychotic indicated for the treatment of adults with schizophrenia. ( 1 )
Contraindications
SECUADO is contraindicated in patients with: Severe hepatic impairment (Child-Pugh C) [see Specific Populations (8.7) , Clinical Pharmacology (12.3) ] . A history of hypersensitivity reactions to asenapine or any components of the transdermal system. Reactions with asenapine have included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing and rash [see Warnings and Precautions (5.6) , Adverse Reactions (6) ].
Severe hepatic impairment (Child-Pugh C). ( 8.7 , 12.3 ) Known hypersensitivity to SECUADO or to any components in the transdermal system. ( 4 , 5.6 , 17 )
Warnings and precautions
Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( 5.3 ) Tardive Dyskinesia: Discontinue if clinically appropriate. ( 5.4 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain.
( 5.5 ) Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing SECUADO if a clinically significant decline in WBC occurs in absence of other causative factors.
( 5.9 ) QT Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. ( 5.10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.12 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.13 ) External Heat: Avoid exposing SECUADO to external heat sources during wear because both the rate and extent of absorption are increased.
( 5.16 ) Application Site Reactions: During wear time or immediately after removal of SECUADO, local skin reactions may occur. Instruct patients to select a different transdermal system application site each day to limit the occurrence of skin reactions. ( 5.17 )
5.1Increased 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 that seen 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. SECUADO is not approved for the treatment of patients with dementia-related psychosis [ see Warnings and Precautions (5.2) ].
5.2Cerebrovascular Adverse Reactions, Including Stroke, In Elderly Patients with Dementia-Related Psychosis
In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. SECUADO is not approved for the treatment of patients with dementia-related psychosis [ see Warnings and Precautions (5.1) ].
5.3Neuroleptic Malignant Syndrome
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
If NMS is suspected, immediately discontinue SECUADO and provide intensive symptomatic treatment and monitoring.
5.4Tardive Dyskinesia
Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs, including SECUADO. The risk appears to be highest among the elderly, especially elderly women, but it is not possible to predict which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible increases with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatment period, even at low doses. It may also occur after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process.
The effect that symptomatic suppression has upon the long-term course of tardive dyskinesia is unknown. Given these considerations, SECUADO should be prescribed in a manner that is most likely to reduce the risk of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients: (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs; and (2) for whom alternative, effective, but potentially less harmful treatments are not available or appropriate.
In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. Periodically reassess the need for continued treatment. If signs and symptoms of tardive dyskinesia appear in a patient on SECUADO, drug discontinuation should be considered. However, some patients may require treatment with SECUADO despite the presence of the syndrome.
5.5Metabolic Changes
Atypical antipsychotic drugs, including SECUADO, have caused metabolic changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and body weight gain. Although all of the drugs in the class to date have been shown to produce some metabolic changes, each drug has its own specific risk profile. Hyperglycemia and Diabetes Mellitus Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics.
There have been reports of hyperglycemia in patients treated with sublingual asenapine. Assess fasting plasma glucose before or soon after initiation of antipsychotic medication, and monitor periodically during long-term treatment. Reports of hyperglycemia in patients treated with SECUADO were <1% in the placebo-controlled trial. Data from the placebo-controlled schizophrenia trial are presented in Table 1 . Table 1: Changes in Fasting Glucose in Adult Patients in the 6-Week, Placebo-Controlled, Fixed Dose Schizophrenia Trial Placebo SECUADO 3.8 mg/24 hours 7.6 mg/24 hours N * = Number of patients who had assessments at both Baseline and Endpoint.
Mean Change from Baseline in Fasting Glucose at Endpoint Change from Baseline (mg/dL) (N*) 0.03 (174) 3.28 (174) 3.72 (172) Proportion of Patients with Shifts from Baseline to Endpoint Normal to High <100 to ≥ 126 mg/dL (n/N*) 0% (0/198) 3.1% (6/196) 3.0% (6/199) Borderline to High ≥100 and < 126 to ≥126 mg/dL (n/N*) 2.0% (4/198) 1.0% (2/196) 1.0% (2/199) In the sublingual asenapine 52-week, double-blind, comparator-controlled trial that included primarily patients with schizophrenia, the mean increase from baseline of fasting glucose was 2.4 mg/dL.
Dyslipidemia Atypical antipsychotics cause adverse alterations in lipids. Before or soon after initiation of antipsychotic medication, obtain a fasting lipid profile at baseline and monitor periodically during treatment. Data from the placebo-controlled schizophrenia trial presented in Table 2 . Table 2: Changes in Lipids in Adult Patients in the 6-Week, Placebo-Controlled, Fixed Dose Schizophrenia Trial Placebo SECUADO 3.8 mg/24 hours 7.6 mg/24 hours N * = Number of patients who had assessments at both Baseline and Endpoint.
Mean Change from Baseline Total Cholesterol (mg/dL)
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Interactions
Antihypertensive drugs: SECUADO may enhance antihypertensive effects. Monitor blood pressure and adjust dosage of antihypertensive drug accordingly. ( 7.1 ) Strong CYP1A2 Inhibitors: Consider dose reduction for SECUADO based on clinical response. ( 7.1 ) Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine dose by half. ( 7.1 )
7.1Drugs Having Clinically Important Drug Interactions with
SECUADO Table 6: Clinically Important Drug Interactions with SECUADO Antihypertensive Drugs Clinical Implication Because of its α 1 -adrenergic antagonism with potential for inducing hypotension, SECUADO may enhance the effects of certain antihypertensive agents [see Warnings and Precautions (5.7) ] . Prevention or Management: Monitor blood pressure and adjust dosage of antihypertensive drug accordingly. Examples: Diuretics, ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers, Alpha-blockers Strong CYP1A2 Inhibitors Clinical Implication Asenapine is metabolized by CYP1A2.
Concomitant use of SECUADO with a CYP1A2 inhibitor increases AUC and C max of asenapine [see Clinical Pharmacology (12.3) ] . Prevention or Management: Dosage reduction for SECUADO based on clinical response may be necessary. Examples: Fluvoxamine, ciprofloxacin, enoxacin CYP2D6 substrates and inhibitors Clinical Implication Asenapine may enhance the inhibitory effects of paroxetine on its own metabolism by CYP2D6. Concomitant use of SECUADO with paroxetine increases paroxetine AUC and C max [see Clinical Pharmacology (12.3) ] .
Prevention or Management: Reduce paroxetine dose by half when paroxetine is used in combination with SECUADO. Examples: Paroxetine
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including SECUADO, during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms.
Studies have not been conducted with SECUADO in pregnant women. There are no available human data informing the drug-associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. No teratogenicity was observed in animal reproduction studies with intravenous administration of asenapine to rats and rabbits during organogenesis at doses 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg of sublingual asenapine twice daily and 1.1 and 0.66 times, respectively, the MRHD of 12.8 mg of transdermal asenapine daily.
In a pre-and post-natal study in rats, intravenous administration of asenapine at doses up to 0.7 times the MRHD of 10 mg of sublingual asenapine twice daily produced increases in post-implantation loss and early pup deaths, and decreases in subsequent pup survival and weight gain [ see Data ]. These doses are up to 1.1 times the MRHD of 12.8 mg transdermal asenapine daily. Advise pregnant women of the potential risk to a fetus.
Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.
Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Data Animal Data In animal studies, asenapine increased post-implantation loss and decreased pup weight and survival at doses similar to or less than recommended clinical doses. In these studies, there was no increase in the incidence of structural abnormalities caused by asenapine. Asenapine was not teratogenic in reproduction studies in rats and rabbits at intravenous doses up to 1.5 mg/kg in rats and 0.44 mg/kg in rabbits administered during organogenesis.
These doses are 0.7 and 0.4 times, respectively, MRHD of 10 mg of sublingual asenapine twice daily and 1.1 and 0.66 times, respectively, the MRHD of 12.8 mg transdermal asenapine daily. Plasma levels of asenapine were measured in the rabbit study, and the area under the curve (AUC) at the highest dose tested was 2 times that in humans receiving the MRHD of 10 mg of sublingual asenapine twice daily. In a study in which rats were treated from day 6 of gestation through day 21 postpartum with intravenous doses of asenapine of 0.3, 0.9, and 1.5 mg/kg/day (0.15, 0.44, and 0.7 times the MRHD of 10 mg of sublingual asenapine twice daily and 0.22, 0.68 and 1.13 times the MRHD of 12.8 mg transdermal asenapine daily), increases in post-implantation loss and early pup deaths were seen at all doses, and decreases in subsequent pup survival and weight gain were seen at the two higher doses.
A cross-fostering study indicated that the decreases in pup survival were largely due to prenatal drug effects. Increases in post-implantation loss and decreases in pup weight and survival were also seen when pregnant rats were dosed orally with asenapine.
Adverse reactions
The following adverse reactions are discussed in more detail in other sections of the labeling: Use in Elderly Patients with Dementia-Related Psychosis [see Warning and Precautions (5.1) ] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.2) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.3) ] Tardive Dyskinesia [see Warnings and Precautions (5.4) ] Metabolic Changes [see Warnings and Precautions (5.5) ] Hypersensitivity Reactions [see Contraindications(4), Warnings and Precautions (5.6) and Patient Counseling Information (17) ] Orthostatic Hypotension, Syncope, and other Hemodynamic Effects [see Warnings and Precautions (5.7) ] Falls [see Warnings and Precautions (5.8) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.9) ] QT Interval Prolongation [see Warnings and Precautions (5.10) ] Hyperprolactinemia [see Warnings and Precautions (5.11) ] Seizures [see Warnings and Precautions (5.12) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.13) ] Body Temperature Regulation [see Warnings and Precautions (5.14) ] Dysphagia [see Warnings and Precautions (5.15) ] External Heat [see Warnings and Precautions (5.16) ] Application Site Reactions [see Warnings and Precautions (5.17) ] Commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo): Extrapyramidal disorder, application site reaction, and weight gain.( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Noven Therapeutics, LLC at 1-800-455-8070 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of SECUADO was evaluated in a total of 315 adult patients diagnosed with schizophrenia who were exposed to SECUADO for up to 6 weeks in a placebo-controlled trial.
Adverse Reactions Leading to Discontinuation of Treatment A total of 4.9% (10/204) patients treated with SECUADO 3.8 mg/24 hours, 7.8% (16/204) patients treated with SECUADO 7.6 mg/24 hours, and 6.8% (14/206) patients on placebo discontinued due to adverse reactions in the placebo-controlled trial. The adverse reaction that most commonly led to discontinuation among SECUADO-treated patients in this trial was akathisia, which led to discontinuation in no (0/204) patients treated with SECUADO 3.8 mg/24 hours, 1.5% (3/204) patients treated with SECUADO 7.6 mg/24 hours, and 0.5% (1/206) patients on placebo.
Commonly Observed Adverse Reactions The most common adverse reactions (≥5% and at least twice the rate of placebo) reported in adult patients with schizophrenia treated with SECUADO in the placebo-controlled trial were extrapyramidal disorder, application site reaction and weight gain. Adverse Reactions Occurring at an Incidence of 2% or More in SECUADO-Treated Patients. Adverse reactions associated with the use of SECUADO (incidence of ≥2%, rounded to the nearest percent, and SECUADO incidence greater than placebo) that occurred during the placebo-controlled trial are shown in Table 5 .
Table 5: Adverse Reactions in ≥2% of Patients in Any SECUADO Dose Group and Which Occurred at Greater Incidence Than in the Placebo Group in 6-Week Schizophrenia Trials * The following terms were combined: Application site reactions includes application site dermatitis, discoloration, discomfort, dryness, edema, erythema, exfoliation, induration, irritation, pain, papules, pruritus, and reaction. Blood glucose increased includes blood glucose increased, blood insulin increased, glycosylated hemoglobin increased, hyperglycemia, Type 2 diabetes mellitus, diabetes mellitus, and hyperinsulinemia.
Hepatic enzyme increased includes hepatic enzyme increased, alanine aminotransferase increased, aspartate aminotransferase increased, and gamma-glutamyltransferase increased. Extrapyramidal symptoms includes dyskinesia, dystonia, extrapyramidal disorder, parkinsonism. tardive dyskinesia, muscle spasm, and musculoskeletal stiffness. Somnolence includes somnolence, sedation, lethargy, and hypersomnia. Hypertension includes hypertension, blood pressure increased, diastolic hypertension, and hypertensive crisis.
System Organ Class/ Preferred Term Placebo N = 206 (%) SECUADO 3.8 mg/24 hours N = 204 (%) 7.6 mg/24 hours N = 204 (%) Gastrointestinal disorders Constipation 4 5 4 Dyspepsia 1 1 3 Diarrhea 1 3 1 General Disorders Application Site Reactions* 4 15 14 Investigations Blood glucose increased* 1 3 1 Weight Increased 2 4 6 Hepatic enzyme increased* 0 2 2 Infections and Infestations Nasopharyngitis 2 3 1 Upper respiratory tract infection 2 3 1 Metabolism and nutrition disorders Increased appetite 0 3 1 Nervous System Disorders Headache 6 9 9 Extrapyramidal symptoms* 2 8 13 Akathisia 2 4 4 Somnolence* 1 4 3 Dystonia 0 1 3 Vascular Disorders Hypertension* 1 2 2 Dose-Related Adverse Reactions : In the placebo-controlled schizophrenia trial, the incidence of an extrapyramidal disorder and weight increased appear to be dose-related (see Table 5 ).
Dystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs.
An elevated risk of acute dystonia is observed in males and younger age groups [ Clinical Pharmacology (12.3) ] . Extrapyramidal Symptoms: In the short-term, placebo-controlled schizophrenia adult trial, data were objectively collected on the Simpson Angus Rating Scale for extrapyramidal symptoms (EPS), the Barnes Akathisia Scale (for akathisia) and the Assessments of Involuntary Movement Scales (for dyskinesias). The mean change from baseline for the SECUADO 3.8 mg/24 hours or 7.6 mg/24 hours treated group was similar to placebo in each of the rating scale scores.
In the short-term, placebo-controlled schizophrenia adult trial, the incidence of reported extrapyramidal disorder events, excluding events related to akathisia, was 7.8% for patients treated with SECUADO 3.8 mg/24 hours, 12.8% for patients treated with SECUADO 7.6 mg/24 hours and 2.4% for placebo-treated patients; and the incidence of akathisia-related events was 3.9% for patients treated with SECUADO 3.8 mg/24 hours, 4.4% for patients treated with SECUADO 7.6 mg/24 hours and 2.4% for placebo-treated patients.
Laboratory Test Abnormalities: Transaminases: Transient elevations in serum transaminases (primarily ALT) were more common in SECUADO-treated patients. The mean increase in ALT levels for SECUADO-treated patients was 6.0 units/L and 3.8 units/L for the SECUADO 3.8 mg/24 hours and 7.6 mg/24 hours treated groups, respectively, compared to a decrease of 1.1 units/L for placebo-treated patients. The proportion of patients with ALT elevations ≥3 times upper limit of normal (ULN) (at any time) was 1.6% and 3.1% for patients treated with SECUADO 3.8 mg/24 hours and 7.6 mg/24 hours, respectively, and 0% for placebo-treated patients.
In a 52-week, double-blind, comparator-controlled trial that included primarily adult patients with schizophrenia, the mean increase from baseline of ALT was 1.7 units/L for sublingual asenapine. Prolactin: The proportion of patients with prolactin elevations ≥4 times ULN (at Endpoint) were 0.0% and 1.3% for patients treated with SECUADO 3.8 mg/24 hours and 7.6 mg/24 hours, respectively, as compared to 2.4% for placebo-treated patient
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Composition
Active ingredients
ASENAPINE 5.7MG/24HR
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
