1 INDICATIONS AND USAGE ADVAIR HFA is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older.

ADVAIR HFA should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta 2 -adrenergic agonist (LABA).

Limitations of Use ADVAIR HFA is not indicated for the relief of acute bronchospasm.

ADVAIR HFA is a combination of fluticasone propionate, an inhaled corticosteroid, and salmeterol, a long-acting beta 2 ‑adrenergic agonist (LABA), indicated for treatment of asthma in adult and adolescent patients aged 12 years and older.

( 1 ) Limitations of use: Not indicated for relief of acute bronchospasm.

( 1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1)] • Oropharyngeal candidiasis [see Warnings and Precautions (5.4)] • Pneumonia in patients with COPD [see Warnings and Precautions (5.5)] • Immunosuppression and risk of infections [see Warnings and Precautions (5.6)] • Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8)] • Cardiovascular and central nervous system effects [see Warnings and Precautions (5.12)] • Reduction in bone mineral density [see Warnings and Precautions (5.13)] • Growth effects [see Warnings and Precautions (5.14)] • Glaucoma and cataracts [see Warnings and Precautions (5.15)] Most common adverse reactions (incidence ≥3%) include: upper respiratory tract infection or inflammation, throat irritation, dysphonia, headache, dizziness, nausea and vomiting.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adult and Adolescent Subjects Aged 12 Years and Older The incidence of adverse reactions associated with ADVAIR HFA in Table 2 is based upon two 12-week, placebo-controlled, U.S.

clinical trials (Trials 1 and 3) and 1 active-controlled 12-week U.S.

clinical trial (Trial 2).

A total of 1,008 adult and adolescent subjects with asthma (556 females and 452 males) previously treated with albuterol alone, salmeterol, or ICS were treated twice daily with 2 inhalations of ADVAIR HFA 45 mcg/21 mcg or ADVAIR HFA 115 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol (44- or 110-mcg doses), salmeterol CFC inhalation aerosol 21 mcg, or placebo HFA inhalation aerosol.

The average duration of exposure was 71 to 81 days in the active treatment groups compared with 51 days in the placebo group.

Table 2.

Adverse Reactions with ADVAIR HFA with ≥3% Incidence in Adult and Adolescent Subjects with Asthma Adverse Event ADVAIR HFA Fluticasone Propionate CFC Inhalation Aerosol Salmeterol CFC Inhalation Aerosol Placebo HFA Inhalation Aerosol 45 mcg/21 mcg (n = 187) % 115 mcg/21 mcg (n = 94) % 44 mcg (n = 186) % 110 mcg (n = 91) % 21 mcg (n = 274) % (n = 176) % Ear, nose, and throat Upper respiratory tract infection 16 24 13 15 17 13 Throat irritation 9 7 12 13 9 7 Upper respiratory inflammation 4 4 3 7 5 3 Hoarseness/dysphonia 3 1 2 0 1 0 Lower respiratory Viral respiratory infection 3 5 4 5 3 4 Neurology Headache 21 15 24 16 20 11 Dizziness 4 1 1 0 <1 0 Gastrointestinal Nausea and vomiting 5 3 4 2 2 3 Viral gastrointestinal infection 4 2 2 0 1 2 Gastrointestinal signs and symptoms 3 2 2 1 1 1 Musculoskeletal Musculoskeletal pain 5 7 8 2 4 4 Muscle pain 4 1 1 1 3 <1 The incidence of common adverse reactions reported in Trial 4, a 12-week non-U.S.

clinical trial in 509 subjects previously treated with ICS who were treated twice daily with 2 inhalations of ADVAIR HFA 230 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol 220 mcg, or 1 inhalation of ADVAIR DISKUS 500 mcg/50 mcg was similar to the incidences reported in Table 2.

Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that occurred in the groups receiving ADVAIR HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following: tachycardia, arrhythmias, myocardial infarction, postoperative complications, wounds and lacerations, soft tissue injuries, ear signs and symptoms, rhinorrhea/postnasal drip, epistaxis, nasal congestion/blockage, laryngitis, unspecified oropharyngeal plaques, dryness of nose, weight gain, allergic eye disorders, eye edema and swelling, gastrointestinal discomfort and pain, dental discomfort and pain, candidiasis mouth/throat, hyposalivation, gastrointestinal infections, disorders of hard tissue of teeth, abdominal discomfort and pain, oral abnormalities, arthralgia and articular rheumatism, muscle cramps and spasms, musculoskeletal inflammation, bone and skeletal pain, muscle injuries, sleep disorders, migraines, allergies and allergic reactions, viral infections, bacterial infections, candidiasis unspecified site, congestion, inflammation, bacterial reproductive infections, lower respiratory signs and symptoms, lower respiratory infections, lower respiratory hemorrhage, eczema, dermatitis and dermatosis, urinary infections.

Laboratory Test Abnormalities In Trial 3, there were more reports of hyperglycemia among adults and adolescents receiving ADVAIR HFA, but this was not seen in Trials 1 and 2.

6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of any formulation of ADVAIR, fluticasone propionate, and/or salmeterol regardless of indication.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to ADVAIR, fluticasone propionate, and/or salmeterol or a combination of these factors.

Cardiovascular Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), hypertension, ventricular tachycardia.

Ear, Nose, and Throat Aphonia, earache, facial and oropharyngeal edema, paranasal sinus pain, rhinitis, throat soreness, tonsillitis.

Endocrine and Metabolic Cushing’s syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism, osteoporosis.

Eye Cataracts, glaucoma.

Gastrointestinal Dyspepsia, xerostomia.

Hepatobiliary Tract and Pancreas Abnormal liver function tests.

Immune System Immediate and delayed hypersensitivity reactions, including rash and rare events of angioedema, bronchospasm, and anaphylaxis.

Infections and Infestations Esophageal candidiasis.

Musculoskeletal Back pain, myositis.

Neurology Paresthesia, restlessness.

Non-Site Specific Fever, pallor.

Psychiatry Agitation, aggression, anxiety, depression.

Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.

Respiratory Asthma; asthma exacerbation; chest congestion; chest tightness; cough; dyspnea; immediate bronchospasm; influenza; paradoxical bronchospasm; tracheitis; wheezing; pneumonia; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.

Skin Contact dermatitis, contusions, ecchymoses, photodermatitis, pruritus.

Urogenital Dysmenorrhea, irregular menstrual cycle, pelvic inflammatory disease, vaginal candidiasis, vaginitis, vulvovaginitis.