Albuterolside effects

The following clinically significant adverse reactions are described elsewhere in labeling:

Deterioration of Asthma

Paradoxical Bronchospasm

Cardiovascular Effects

Hypersensitivity Reactions, including Anaphylaxis

Hypokalemia

Immunosuppression and Risk of Infections

Oropharyngeal Candidiasis

Hypercorticism and Adrenal Suppression

Reduction in Bone Mineral Density

Glaucoma and Cataracts

Effects on Growth in Pediatric Patients Most common adverse reactions (incidence ≥ 1%) are headache, oral candidiasis, cough, dysphonia. To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 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 AIRSUPRA is based on data from 3 trials: MANDALA, DENALI and BATURA. All reported safety data is based on patients who received AIRSUPRA 180 mcg/160 mcg. While patients 12 to 17 years of age were included in these trials, AIRSUPRA is not approved in this age group. In MANDALA, AIRSUPRA 180 mcg/160 mcg was administered as needed in patients with asthma who were receiving medium to high dose ICS or low to high dose ICS/LABA, with or without another controller medicine as maintenance therapy. A total of 1015 patients 12 to 84 years of age (mean age: 51 years) received at least one dose of AIRSUPRA and participated in the study for a mean duration of 310 days. Of these, 905 patients were exposed for at least 24 weeks and 323 patients had exposure for at least 1 year. The mean daily use was 2.6 actuations. On the majority of study days, patients used 2 or less actuations; more than 8 actuations were used on less than 2% of study days. The incidence of common adverse reactions in MANDALA is described in Table 1. Table 1 Summary of Adverse Reactions with AIRSUPRA Reported in ≥ 1% of Patients (MANDALA) Adverse Reaction AIRSUPRA 180 mcg/160 mcg N = 1015 (%) AS MDI 1 180 mcg N = 1015 (%) Headache 44 50 Oral candidiasis 2 13 5 Cough 10 11 1 Albuterol Metered Dose Inhaler = AS MDI 2 Oral candidiasis also includes those reactions reported under the preferred term oropharyngeal candidiasis. The safety profile of AIRSUPRA in MANDALA was similar to that observed with AS MDI, irrespective of background ICS dose. In DENALI, AIRSUPRA 180 mcg/160 mcg was administered 4 times a day for 12 weeks in patients with asthma who were previously treated with as-needed short-acting beta 2 -agonists (SABA) alone or with low-dose ICS maintenance therapy plus as-needed SABA. A total of 197 patients 13 to 81 years of age (mean age: 50 years) received at least one dose of AIRSUPRA. The adverse reactions profile was similar to MANDALA except for the following adverse reactions for AIRSUPRA with an incidence ≥ 1.0% that exceeded the incidence in MANDALA: headache (5.1%), dysphonia (2.0%), and oral/oropharyngeal candidiasis (1.5%), compared to headache (7.1%), dysphonia (0%), and oral/oropharyngeal candidiasis (0%) in the placebo arm. In BATURA, AIRSUPRA 180 mcg/160 mcg was administered as needed for 12 to 52 weeks in patients with asthma who were previously treated with as-needed SABA alone, or as-needed SABA plus background maintenance of either low-dose ICS or leukotriene receptor antagonist (LTRA). The 26% of patients on background ICS or LTRA were instructed to continue these treatments throughout the study period. A total of 1209 patients 12 to 95 years of age (mean age: 43 years) received at least one dose of AIRSUPRA and participated in the study for a mean duration of 259 days. Of them, 1109 patients were exposed for at least 12 weeks and 258 patients were exposed for at least 1 year. The mean daily use was 1.5 actuations for AIRSUPRA and 1.8 actuations for AS MDI 180 mcg. On the majority of study days, patients used 2 or less actuations of AIRSUPRA or AS MDI 180 mcg; more than 8 actuations were used on 2% of study days for patients on AIRSUPRA and 4% of study days for patients on AS MDI 180 mcg. The safety profile of AIRSUPRA in BATURA was similar to that in MANDALA.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of budesonide or albuterol. 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.

Cardiovascular disorders: myocardial ischemia, tremor, tachycardia, palpitations, extrasystoles, arrhythmias (including atrial fibrillation, supraventricular tachycardia), syncope, hypertension, peripheral vasodilatation Endocrine disorders: signs or symptoms of systemic glucocorticosteroid effect (including hypofunction of the adrenal gland and reduction of growth rate) Eye disorders: cataracts, glaucoma, increased intraocular pressure Immune system disorders: immediate and delayed hypersensitivity reactions (including anaphylactic reaction, angioedema, bronchospasm, rash, contact dermatitis and urticaria) General disorders: fever, weight gain, taste perversion, flu syndrome Gastrointestinal disorders: nausea, vomiting, dyspepsia, diarrhea Infections: sinusitis, pharyngitis, respiratory tract infection, nasopharyngitis, gastroenteritis, otitis media, laryngitis Metabolic disorders: hypokalemia, metabolic acidosis Musculoskeletal disorders: hypertonia, musculoskeletal pain, myalgia, asthenia, arthralgia, muscle cramps, fracture Neurological or psychiatric system disorders: migraine, dizziness, central nervous system stimulation, insomnia, hyperactivity, psychiatric symptoms (including psychosis, depression, aggressive reactions, irritability, nervousness, restlessness, behavioral disturbances and anxiety) Respiratory, thoracic, and mediastinal disorders: rhinitis, nasal congestion, throat irritation, oropharyngeal edema, upper respiratory inflammation, drying or irritation of the oropharynx Skin and subcutaneous tissue disorders: skin bruising, ecchymosis