1 INDICATIONS AND USAGE FLOVENT DISKUS is indicated for the maintenance treatment of asthma as prophylactic therapy in patients aged 4 years and older.

Important Limitation of Use FLOVENT DISKUS is NOT indicated for the relief of acute bronchospasm.

FLOVENT DISKUS is an inhaled corticosteroid indicated for: • Maintenance treatment of asthma as prophylactic therapy in patients aged 4 years and older.

( 1 ) Important limitation: • Not indicated for relief of acute bronchospasm.

( 1 )

6 ADVERSE REACTIONS Systemic and local corticosteroid use may result in the following: • Candida albicans infection [see Warnings and Precautions (5.1)] • Immunosuppression [see Warnings and Precautions (5.3)] • Hypercorticism and adrenal suppression [see Warnings and Precautions (5.5)] • Reduction in bone mineral density [see Warnings and Precautions (5.7)] • Growth effects [see Warnings and Precautions (5.8)] • Glaucoma and cataracts [see Warnings and Precautions (5.9)] Most common adverse reactions (incidence >3%) include upper respiratory tract infection or inflammation, throat irritation, sinusitis, rhinitis, oral candidiasis, nausea and vomiting, gastrointestinal discomfort, fever, cough, bronchitis, and headache.

( 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.

The incidence of common adverse reactions in Table 1 is based upon 7 placebo-controlled U.S.

clinical trials in which 1,176 pediatric, adolescent, and adult subjects (466 females and 710 males) previously treated with as-needed bronchodilators and/or inhaled corticosteroids were treated twice daily for up to 12 weeks with FLOVENT DISKUS (doses of 50 to 500 mcg) or placebo.

Table 1.

Adverse Reactions with FLOVENT DISKUS with >3% Incidence and More Common than Placebo in Subjects with Asthma Adverse Event FLOVENT DISKUS 50 mcg Twice Daily (n = 178) % FLOVENT DISKUS 100 mcg Twice Daily (n = 305) % FLOVENT DISKUS 250 mcg Twice Daily (n = 86) % FLOVENT DISKUS 500 mcg Twice Daily (n = 64) % Placebo (n = 543) % Ear, nose, and throat Upper respiratory tract infection 20 18 21 14 16 Throat irritation 13 13 3 22 8 Sinusitis/sinus infection 9 10 6 6 6 Upper respiratory inflammation 5 5 0 5 3 Rhinitis 4 3 1 2 2 Oral candidiasis <1 9 6 5 7 Gastrointestinal Nausea and vomiting 8 4 1 2 4 Gastrointestinal discomfort and pain 4 3 2 2 3 Viral gastrointestinal infection 4 3 3 5 1 Non-site specific Fever 7 7 1 2 4 Viral infection 2 2 0 5 2 Lower respiratory Viral respiratory infection 4 5 1 2 4 Cough 3 5 1 5 4 Bronchitis 2 3 0 8 1 Neurological Headache 12 12 2 14 7 Musculoskeletal and trauma Muscle injury 2 0 1 5 1 Musculoskeletal pain 4 3 2 5 2 Injury 2 <1 0 5 <1 Table 1 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in any of the groups treated with FLOVENT DISKUS and were more common than in the placebo group.

Less than 2% of subjects discontinued from the trials because of adverse reactions.

The average duration of exposure was 73 to 79 days in the active treatment groups compared with 56 days in the placebo group.

Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with asthma treated with FLOVENT DISKUS compared with subjects treated with placebo include the following: palpitations; soft tissue injuries; contusions and hematomas; wounds and lacerations; burns; poisoning and toxicity; pressure-induced disorders; hoarseness/dysphonia; epistaxis; ear, nose, throat, and tonsil signs and symptoms; ear, nose, and throat polyps; allergic ear, nose, and throat disorders; throat constriction; fluid disturbances; weight gain; appetite disturbances; keratitis and conjunctivitis; blepharoconjunctivitis; gastrointestinal signs and symptoms; oral ulcerations; dental discomfort and pain; oral erythema and rashes; mouth and tongue disorders; oral discomfort and pain; tooth decay; cholecystitis; arthralgia and articular rheumatism; muscle cramps and spasms; musculoskeletal inflammation; dizziness; sleep disorders; migraines; paralysis of cranial nerves; edema and swelling; bacterial infections; fungal infections; mobility disorders; mood disorders; bacterial reproductive infections; photodermatitis; dermatitis and dermatosis; viral skin infections; eczema; pruritus; acne and folliculitis; urinary infections.

Three (3) of the 7 placebo-controlled U.S.

clinical trials were pediatric trials.

A total of 592 subjects aged 4 to 11 years were treated with FLOVENT DISKUS (dosages of 50 or 100 mcg twice daily) or placebo; an additional 174 subjects aged 4 to 11 years received FLOVENT ROTADISK (fluticasone propionate inhalation powder) at the same doses.

There were no clinically relevant differences in the pattern or severity of adverse events in children compared with those reported in adults.

In the first 16 weeks of a 52-week clinical trial in adult subjects with asthma who previously required oral corticosteroids (daily doses of 5 to 40 mg oral prednisone), the effects of FLOVENT DISKUS 500 mcg twice daily (n = 41) and 1,000 mcg twice daily (n = 36) were compared with placebo (n = 34) for the frequency of reported adverse events.

The average duration of exposure for subjects taking FLOVENT DISKUS was 105 days compared with 75 days for placebo.

Adverse events, whether or not considered drug related by the investigators, reported in more than 5 subjects in the group taking FLOVENT DISKUS and that occurred more frequently with FLOVENT DISKUS than with placebo are shown below (percent FLOVENT DISKUS and percent placebo).

Ear, Nose, and Throat: Hoarseness/dysphonia (9% and 0%), nasal congestion/blockage (16% and 0%), oral candidiasis (31% and 21%), rhinitis (13% and 9%), sinusitis/sinus infection (33% and 12%), throat irritation (10% and 9%), and upper respiratory tract infection (31% and 24%).

Gastrointestinal: Nausea and vomiting (9% and 0%).

Lower Respiratory: Cough (9% and 3%) and viral respiratory infections (9% and 6%).

Musculoskeletal: Arthralgia and articular rheumatism (17% and 3%) and muscle pain (12% and 0%).

Non-Site Specific: Malaise and fatigue (16% and 9%) and pain (10% and 3%).

Skin: Pruritus (6% and 0%) and skin rashes (8% and 3%).

6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of fluticasone propionate.

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 fluticasone propionate or a combination of these factors.

Ear, Nose, and Throat Aphonia, facial and oropharyngeal edema, and throat soreness.

Endocrine and Metabolic Cushingoid features, growth velocity reduction in children/adolescents, hyperglycemia, and osteoporosis.

Eye Cataracts.

Immune System Disorders Immediate and delayed hypersensitivity reactions, including anaphylaxis, rash, angioedema, and bronchospasm, have been reported.

Anaphylactic reactions in patients with severe milk protein allergy have been reported.

Infections and Infestations Esophageal candidiasis.

Psychiatry Agitation, aggression, anxiety, depression, and restlessness.

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

Respiratory Asthma exacerbation, bronchospasm, chest tightness, dyspnea, immediate bronchospasm, pneumonia, and wheeze.

Skin Contusions and ecchymoses.