HIGHLIGHTS OF PRESCRIBING INFORMATION • Primary treatment of status asthmaticus or acute episodes of asthma or These highlights do not include all the information needed to use COPD requiring intensive measures. (4) SEREVENT DISKUS safely and effectively. See full prescribing • Severe hypersensitivity to milk proteins or demonstrated hypersensitivity information for SEREVENT DISKUS. to salmeterol or any of the excipients. (4) SEREVENT DISKUS (salmeterol xinafoate inhalation powder), for oral -------------------------- WARNINGS AND PRECAUTIONS -------------------------- inhalation use • LABA as monotherapy (without ICS) for asthma increase the risk of Initial U.S. Approval: 1994 asthma-related death and asthma-related hospitalizations. Prescribe for asthma only as concomitant therapy with an inhaled corticosteroid. (5.1) WARNING: ASTHMA-RELATED DEATH • Do not initiate in acutely deteriorating asthma or COPD. Do not use to See full prescribing information for complete boxed warning. treat acute symptoms. (5.2) • Not a substitute for corticosteroids. Patients with asthma must take a • Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, the active ingredient in SEREVENT DISKUS, as monotherapy concomitant ICS. (5.3) (without inhaled corticosteroids [ICS]) increase the risk of • Do not use in combination with an additional medicine containing a asthma-related death. A U.S. trial showed an increase in LABA because of risk of overdose. (5.4) asthma-related deaths in subjects receiving salmeterol (13 deaths out • If paradoxical bronchospasm occurs, discontinue SEREVENT DISKUS of 13,176 subjects treated for 28 weeks on salmeterol versus 3 out of and institute alternative therapy. (5.5) 13,179 subjects on placebo). When LABA are used in fixed-dose • Use with caution in patients with cardiovascular or central nervous system combination with ICS, data from large clinical trials do not show a disorders because of beta-adrenergic stimulation. (5.6) significant increase in the risk of serious asthma-related events • Use with caution in patients with convulsive disorders, thyrotoxicosis, (hospitalizations, intubations, death) compared with ICS alone. (5.1) diabetes mellitus, and ketoacidosis. (5.9) • Prescribe SEREVENT DISKUS only as additional therapy for • Be alert to hypokalemia and hyperglycemia. (5.10) patients with asthma who are currently taking but are inadequately controlled on an ICS. Do not use SEREVENT DISKUS for patients ---------------------------------- ADVERSE REACTIONS---------------------------------- whose asthma is adequately controlled on low- or medium-dose ICS. Most common adverse reactions (incidence ≥5%) are: (1.1, 5.1) • Asthma: Headache, influenza, nasal/sinus congestion, pharyngitis, • Available data from controlled clinical trials suggest that LABA as rhinitis, tracheitis/bronchitis. (6.1) monotherapy increase the risk of asthma-related hospitalization in • COPD: Cough, headache, musculoskeletal pain, throat irritation, viral pediatric and adolescent patients. (5.1) respiratory infection. (6.2) To report SUSPECTED ADVERSE REACTIONS, contact ------------------------------- INDICATIONS AND USAGE ------------------------------ SEREVENT DISKUS is a LABA indicated for: GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. • Treatment of asthma in patients aged 4 years and older with an ICS. (1.1) • Prevention of exercise-induced bronchospasm (EIB) in patients aged ---------------------------------- DRUG INTERACTIONS---------------------------------- 4 years and older. (1.2) • Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): • Maintenance treatment of bronchospasm associated with chronic Use not recommended. May increase risk of cardiovascular effects. (7.1) obstructive pulmonary disease (COPD). (1.3) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with Important limitation of use: Not indicated for relief of acute bronchospasm. extreme caution. May potentiate effect of salmeterol on vascular system. (1.1, 1.3) (7.2) • Beta-blockers: Use with caution. May block bronchodilatory effects of --------------------------DOSAGE AND ADMINISTRATION ------------------------- beta-agonists and produce severe bronchospasm. (7.3) • For oral inhalation only. (2) • Diuretics: Use with caution. Electrocardiographic changes and/or • Treatment of asthma in patients aged 4 years and older: 1 inhalation twice hypokalemia associated with non–potassium-sparing diuretics may daily in addition to concomitant treatment with an ICS. (2.1) worsen with concomitant beta-agonists. (7.4) • EIB: 1 inhalation at least 30 minutes before exercise. (2.2) • Maintenance treatment of bronchospasm associated with COPD: 1 -------------------------- USE IN SPECIFIC POPULATIONS-------------------------- inhalation twice daily. (2.3) Hepatic impairment: Monitor patients for signs of increased drug exposure. (8.6) ------------------------ DOSAGE FORMS AND STRENGTHS------------------------ Inhalation powder: Inhaler containing salmeterol (50 mcg) as a powder See 17 for PATIENT COUNSELING INFORMATION and Medication formulation for oral inhalation. (3) Guide. ---------------------------------- CONTRAINDICATIONS --------------------------------- Revised: 1/2020 • Asthma: Without concomitant use of an ICS. (4) ______________________________________________________________________________________________________________________________________________ FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: ASTHMA-RELATED DEATH 5.6 Cardiovascular and Central Nervous System Effects 1 INDICATIONS AND USAGE 5.7 Immediate Hypersensitivity Reactions 1.1 Treatment of Asthma 5.8 Drug Interactions with Strong Cytochrome P450 3A4 1.2 Prevention of Exercise-Induced Bronchospasm Inhibitors 1.3 Maintenance Treatment of Chronic Obstructive Pulmonary 5.9 Coexisting Conditions Disease 5.10 Hypokalemia and Hyperglycemia 2 DOSAGE AND ADMINISTRATION 6 ADVERSE REACTIONS 2.1 Asthma 6.1 Clinical Trials Experience in Asthma 2.2 Exercise-Induced Bronchospasm 6.2 Clinical Trials Experience in Chronic Obstructive 2.3 Chronic Obstructive Pulmonary Disease Pulmonary Disease 3 DOSAGE FORMS AND STRENGTHS 6.3 Postmarketing Experience 4 CONTRAINDICATIONS 7 DRUG INTERACTIONS 5 WARNINGS AND PRECAUTIONS 7.1 Inhibitors of Cytochrome P450 3A4 5.1 Asthma-Related Death 7.2 Monoamine Oxidase Inhibitors and Tricyclic 5.2 Deterioration of Disease and Acute Episodes Antidepressants 5.3 SEREVENT DISKUS is Not a Substitute for 7.3 Beta-adrenergic Receptor Blocking Agents Corticosteroids 7.4 Non–Potassium-Sparing Diuretics 5.4 Excessive Use of SEREVENT DISKUS and Use with Other 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Long-acting Beta2-agonists 5.5 Paradoxical Bronchospasm and Upper Airway Symptoms 8.2 Lactation 1 8.4 Pediatric Use 13.2 Animal Toxicology and/or Pharmacology 8.5 Geriatric Use 14 CLINICAL STUDIES 8.6 Hepatic Impairment 14.1 Asthma 10 OVERDOSAGE 14.2 Exercise-Induced Bronchospasm 11 DESCRIPTION 14.3 Chronic Obstructive Pulmonary Disease 12 CLINICAL PHARMACOLOGY 16 HOW SUPPLIED/STORAGE AND HANDLING 12.1 Mechanism of Action 17 PATIENT COUNSELING INFORMATION 12.2 Pharmacodynamics *Sections or subsections omitted from the full prescribing information are not 12.3 Pharmacokinetics listed. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility ____________________________________________________________________________________________________________________________________ FULL PRESCRIBING INFORMATION WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, the active ingredient in SEREVENT DISKUS, as monotherapy (without inhaled corticosteroids [ICS]) increase the risk of asthma-related death. Data from a large placebo-controlled U.S. trial that compared the safety of salmeterol with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol (13 deaths out of 13,176 subjects treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 subjects on placebo). Use of background ICS was not required in this study. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Use of SEREVENT DISKUS for the treatment of asthma as monotherapy without a concomitant ICS is contraindicated. Use SEREVENT DISKUS only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on an ICS. Do not use SEREVENT DISKUS for patients whose asthma is adequately controlled on low- or medium-dose ICS. Pediatric and Adolescent Patients Available data from controlled clinical trials suggest that LABA as monotherapy increase the risk of asthma-related hospitalization in pediatric and adolescent patients. For pediatric and adolescent patients with asthma who require addition of a LABA to an ICS, a fixed-dose combination product containing both an ICS and a LABA should ordinarily be used to ensure adherence with both drugs. In cases where use of an ICS and a LABA is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components. If adherence cannot be assured, a fixed-dose combination product containing both an ICS and a LABA is recommended. 1 INDICATIONS AND USAGE 1.1 Treatment of Asthma SEREVENT DISKUS is indicated for the treatment of asthma and in the prevention of bronchospasm