SECUADO

RECENT MAJOR CHANGES WARNINGS AND PRECAUTIONS ( 5.11 ) 1/2025

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 )

2 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) ].

3 DOSAGE FORMS AND STRENGTHS SECUADO (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 )

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 )

6 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 . 6.1 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 hepati …

7 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

8 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 …

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.

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

10 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.

16 HOW SUPPLIED/STORAGE AND HANDLING 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] .