Secuado
Asenapine · Film, Extended Release · Transdermal
Uses
1 INDICATIONS AND USAGE 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 )
Dosage and administration
For transdermal use only. ( 2.2 ) Apply one SECUADO transdermal system every 24 hours. ( 2.2 ) Apply SECUADO to one of the following sites: the hip, abdomen, upper arm, or upper back area. ( 2.2 ) The recommended starting dose of SECUADO is 3.8 mg/24 hours. May increase dosage to 5.7 mg/24 hours or 7.6 mg/24 hours after one week. ( 2.1 ) 2.1 Schizophrenia Initiate SECUADO at a dosage of 3.8 mg/24 hours. In a short-term, placebo-controlled trial, there was no suggestion of added benefit at a dosage of 7.6 mg/24 hours, on average, but there was an increase in certain adverse reactions. The dosage may be increased to 5.7 mg/24 hours or 7.6 mg/24 hours, as needed, after one week. The safety of doses above 7.6 mg/24 hours has not been evaluated in clinical studies [ see Clinical Studies (14) ]. Based on the average exposure (AUC) of asenapine, SECUADO 3.8 mg/24 hours corresponds to 5 mg twice daily of sublingual asenapine and SECUADO 7.6 mg/24 hours corresponds to 10 mg twice daily of sublingual asenapine [ see Clinical Pharmacology (12.3) ]. 2.2 Important Application Instructions See the FDA-approved patient labeling ( Instructions for Use ). SECUADO transdermal system is applied once daily. Each SECUADO transdermal system should be worn for 24 hours only. Instruct patients to wear only one SECUADO transdermal system at any time. Apply SECUADO to clean, dry, and intact skin at the selected application site. Application sites include: the upper arm, upper back, abdomen, or hip. Apply the transdermal system to a different application site each time a new SECUADO transdermal system is applied. Do not cut open the pouch until ready to apply SECUADO and do not use the transdermal system if the individual pouch seal is broken or if it appears to be damaged. Do not cut SECUADO, the whole transdermal system should be applied. If the SECUADO transdermal system lifts at the edges, reattach SECUADO by pressing firmly and smoothing down the edges of the system. If SECUADO comes off completely, apply a new SECUADO transdermal system. Discard SECUADO by folding the used transdermal system so that the adhesive side sticks to itself and safely discard. If irritation or a burning sensation occurs while wearing SECUADO, remove the system and apply a new transdermal system to a new application site [ see Warnings and Precautions (5.17) ]. Showering is permitted, but the use of SECUADO during swimming or taking a bath has not been evaluated. Do not apply external heat sources (e.g., heating pad) over the SECUADO transdermal system [ see Warnings and Precautions (5.16) ]. Prolonged application of heat over a SECUADO transdermal system increases plasma concentrations of asenapine [ see Clinical Pharmacology (12.3) ].
Dosage forms and strengths
(asenapine) transdermal system is a translucent rounded square product available in three dosage strengths: 3.8 mg asenapine / 24 hours 5.7 mg asenapine / 24 hours 7.6 mg asenapine / 24 hours Transdermal System: 3.8 mg/24 hours, 5.7 mg/24 hours and 7.6 mg/24 hours ( 3 )
Contraindications
4 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 ) 5.1 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 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) ]. 5.2 Cerebrovascular 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) ]. 5.3 Neuroleptic 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. 5.4 Tardive 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. 5.5 Metabolic 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.
Side effects
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 . 6.1 Clinical 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) ] .
Drug 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 ) 7.1 Drugs 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
Use in specific populations
Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) 8.1 Pregnancy 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. 8.2 Lactation Risk Summary Lactation studies have not been conducted to assess the presence of asenapine in human milk, the effects of asenapine on the breastfed infant, or the effects of asenapine on milk production. Asenapine is excreted in rat milk. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for SECUADO and any potential adverse effects on the breastfed infant from SECUADO or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of SECUADO in pediatric patients have not been established. Efficacy of sublingual asenapine was not demonstrated in an 8-week, placebo-controlled, double-blind trial, in 306 adolescent patients aged 12 to 17 years with schizophrenia at doses of 2.5 and 5 mg twice daily. The most common adverse reactions (proportion of patients equal or greater than 5% and at least twice placebo) reported were somnolence, akathisia, dizziness, and oral hypoesthesia or paresthesia. The proportion of patients with an equal or greater than 7% increase in body weight at endpoint compared to baseline for placebo, sublingual asenapine 2.5 mg twice daily, and sublingual asenapine 5 mg twice daily was 3%, 10%, and 10%, respectively. No new major safety findings were reported from a 26-week, open-label, uncontrolled safety trial in pediatric patients with schizophrenia treated with sublingual asenapine. Juvenile Animal Data Subcutaneous administration of asenapine to juvenile rats for 56 days from day 14 of age to day 69 of age at 0.4, 1.2, and 3.2 mg/kg/day (0.2, 0.6 and 1.5 times the maximum recommended human dose of 10 mg twice daily given sublingually on a mg/m 2 basis) resulted in significant reduction in body weight gain in animals of both sexes at all dose levels from the start of dosing until weaning. Body weight gain remained reduced in males to the end of treatment, however, recovery was observed once treatment ended.
Pregnancy
8.1 Pregnancy 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.
Pediatric use
8.4 Pediatric Use Safety and effectiveness of SECUADO in pediatric patients have not been established. Efficacy of sublingual asenapine was not demonstrated in an 8-week, placebo-controlled, double-blind trial, in 306 adolescent patients aged 12 to 17 years with schizophrenia at doses of 2.5 and 5 mg twice daily. The most common adverse reactions (proportion of patients equal or greater than 5% and at least twice placebo) reported were somnolence, akathisia, dizziness, and oral hypoesthesia or paresthesia. The proportion of patients with an equal or greater than 7% increase in body weight at endpoint compared to baseline for placebo, sublingual asenapine 2.5 mg twice daily, and sublingual asenapine 5 mg twice daily was 3%, 10%, and 10%, respectively. No new major safety findings were reported from a 26-week, open-label, uncontrolled safety trial in pediatric patients with schizophrenia treated with sublingual asenapine. Juvenile Animal Data Subcutaneous administration of asenapine to juvenile rats for 56 days from day 14 of age to day 69 of age at 0.4, 1.2, and 3.2 mg/kg/day (0.2, 0.6 and 1.5 times the maximum recommended human dose of 10 mg twice daily given sublingually on a mg/m 2 basis) resulted in significant reduction in body weight gain in animals of both sexes at all dose levels from the start of dosing until weaning. Body weight gain remained reduced in males to the end of treatment, however, recovery was observed once treatment ended. Neurobehavioral assessment indicated increased motor activity in animals at all dose levels following the completion of treatment, with the evidence of recovery in males. There was no recovery after the end of treatment in female activity pattern as late as day 30 following the completion of treatment (last retesting). Therefore, a No Observed Adverse Effect Level (NOAEL) for the juvenile animal toxicity of asenapine could not be determined. There were no treatment-related effects on the startle response, learning/memory, organ weights, microscopic evaluations of the brain and, reproductive performance (except for minimally reduced conception rate and fertility index in males and females administered 1.2 and 3.2 mg/kg/day).
Geriatric use
8.5 Geriatric Use The SECUADO placebo-controlled trial for the treatment of schizophrenia did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. Of the approximately 614 patients in placebo-controlled study of SECUADO, 1.6% (10) were 65 years of age or over. Multiple factors that might increase the pharmacodynamic response to SECUADO, causing poorer tolerance or orthostasis, could be present in elderly patients, and these patients should be monitored carefully. Based on a pharmacokinetic study in elderly patients with sublingual asenapine, dosage adjustments are not recommended based on age alone [ see Clinical Pharmacology (12.3) ]. Elderly patients with dementia-related psychosis treated with SECUADO are at an increased risk of death compared to placebo. SECUADO is not approved for the treatment of patients with dementia-related psychosis [ see Warning and Precautions (5.1 , 5.2) ].
Overdosage
Human Experience : In the placebo-controlled trial in adults for SECUADO, there were no reports of accidental or intentional acute overdosage of SECUADO. In adult clinical studies involving more than 3350 patients and/or healthy subjects for sublingual asenapine, accidental or intentional acute overdosage of sublingual asenapine was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion of sublingual asenapine was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion. Management of Overdosage : There is no specific antidote to SECUADO. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Consult a Certified Poison Control Center at 1 800-222-1222 for up to date information on the management of overdosage. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of SECUADO-induced alpha blockade). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.
Description
11 DESCRIPTION SECUADO transdermal system contains asenapine, an atypical antipsychotic. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical name is trans -5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7] oxepino [4,5-c] pyrrole. Its molecular formula is C 17 H 16 Cl NO and its molecular weight is 285.8 g/mol. The chemical structure is: SECUADO is for transdermal administration and is provided in three strengths: 3.8 mg, 5.7 mg or 7.6 mg asenapine every 24 hours ( Table 7 ). The composition of the transdermal systems per unit area is identical. Inactive ingredients include alicyclic saturated hydrocarbon resin, butylated hydroxytoluene, isopropyl palmitate, maleate salts (monosodium maleate and disodium maleate), mineral oil, polyester film backing, polyisobutylene, silicone-treated polyester release liner, sodium acetate anhydrous, and styrene-isoprene-styrene block copolymer. Table 7: SECUADO (asenapine) transdermal system Dosage Strength (Asenapine) Total Asenapine Content per Transdermal System Transdermal System Size 3.8 mg/24 hours 6.4 mg 20 cm 2 5.7 mg/24 hours 9.6 mg 30 cm 2 7.6 mg/24 hours 12.8 mg 40 cm 2 chemical structure
Mechanism of action
12.1 Mechanism of Action The mechanism of action of asenapine in schizophrenia is unclear. However, it’s efficacy in schizophrenia could be mediated through a combination of antagonist activity at D 2 and 5-HT 2A receptors.
How supplied
16.1 How Supplied SECUADO (asenapine) transdermal system is a translucent rounded square product with a printed backing on one side and a release liner on the other supplied as: 3.8 mg/24 hours transdermal system (system size: 20 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0172-3 5.7 mg/24 hours transdermal system (system size: 30 cm 2 ) Carton of 30 systems, each system is packaged into an individual pouch NDC 68968-0173-3 7.6 mg/24 hours transdermal system (system size: 40 cm 2 ) Carton of 30 transdermal systems, each transdermal system is packaged in an individual pouch NDC 68968-0174-3 16.2 Storage Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (between 59°F and 86°F) [see USP Controlled Room Temperature] .
Storage
16.2 Storage Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C and 30°C (between 59°F and 86°F) [see USP Controlled Room Temperature] .
Patient information
Advise the patient to read the FDA-approved patient labeling ( Instructions for Use ). Hypersensitivity Reactions Counsel patients on the signs and symptoms of a serious allergic reaction (e.g., difficulty breathing, itching, swelling of the face, tongue or throat, feeling lightheaded etc.) and to seek immediate emergency assistance if they develop any of these signs and symptoms [ see Contraindications (4), Warnings and Precautions (5.6) ]. Neuroleptic Malignant Syndrome Counsel patients about a potentially fatal adverse reaction referred to as NMS that has been reported in association with administration of antipsychotic drugs. Advise patients to contact a healthcare provider or report to the emergency room if they experience signs or symptoms of NMS including hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [ see Warnings and Precautions (5.3) ]. Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their health care provider if these abnormal movements occur [ see Warnings and Precautions (5.4) ]. Metabolic Changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia, and Weight Gain) Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia (high blood sugar) and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [ see Warnings and Precautions (5.5) ]. Orthostatic Hypotension Counsel patients about the risk of orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing) especially early in treatment, and at times of re-initiating treatment or increases in dose [ see Warnings and Precautions (5.7) ]. Leukopenia/Neutropenia Advise patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia they should have their CBC monitored while taking SECUADO [ see Warnings and Precautions (5.9) ]. Hyperprolactinemia Counsel patients on the signs and symptoms of hyperprolactinemia and to contact their health care provider if these abnormalities occur [ see Warnings and Precautions (5.11) ]. Interference with Cognitive and Motor Performance Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that SECUADO therapy does not affect them adversely [ see Warnings and Precautions (5.13) ]. Heat Exposure and Dehydration Counsel patients regarding appropriate care in avoiding overheating and dehydration [ see Warnings and Precautions (5.14) ]. External Heat Inform patients to avoid exposing SECUADO to external heat sources, such as hair dryers, heating pads, electric blankets, heated water beds, etc., [ see Warnings and Precautions (5.16) ]. Application Site Reactions Inform patients that application site reactions, including erythema, pruritus, papules, discomfort, pain, edema or irritation, have been reported with use of SECUADO. Inform patients that increased skin irritation may occur if applied for a longer period than instructed or if the same application site is used repeatedly. Instruct patients to select a different application site each day to minimize skin reactions. Patients should monitor for these reactions while wearing or immediately after removal of SECUADO [ see Warnings and Precautions (5.17) ]. Concomitant Medications Advise patients to inform their health care provider if they are taking, or plan to take, any prescription or over-the-counter medications since there is a potential for interactions [ see Drug Interactions (7.1) ]. Pregnancy Advise patients that SECUADO may cause fetal harm as well as extrapyramidal and/or withdrawal symptoms in a neonate. Advise patients to notify their healthcare provider with a known or suspected pregnancy [ see Use in Specific Populations (8.1) ]. Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SECUADO during pregnancy [see Use in Specific Populations (8.1) ] . Manufactured by: Hisamitsu Pharmaceutical Co. Inc., 408, Tashirodaikan-machi, Tosu, Saga, Japan Distributed by: Noven Therapeutics, LLC, Miami, Florida USA. For more information, call 1-800-455-8070 or visit www.secuado.com SECUADO is a registered trademark of Hisamitsu Pharmaceutical Co., Inc. ©2019-2025 Hisamitsu Pharmaceutical Co., Inc. All rights reserved. 5O134A-0
Label text from the FDA structured product label by Noven Therapeutics, LLC (revised Jan 30, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Asenapine in 3 products
Secuado NDC products (3)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68968-0172 | Asenapine 3.8 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-0173 | Asenapine 5.7 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
| 68968-0174 | Asenapine 7.6 mg/d Film, Extended Release | Noven Therapeutics, LLC | NDA |
Frequently asked questions
What is Secuado used for?
1 INDICATIONS AND USAGE 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 )
What are the side effects of Secuado?
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)… See the full label for the complete list.
Who makes Secuado?
Secuado is listed by 1 labeler in the FDA NDC directory, including Noven Therapeutics, LLC.