1 INDICATIONS AND USAGE Albuterol sulfate inhalation aerosol is a beta 2 -adrenergic agonist indicated for: • Treatment or prevention of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease.

( 1.1 ) • Prevention of exercise-induced bronchospasm in patients 4 years of age and older.

( 1.2 ) 1.1 Bronchospasm Albuterol sulfate inhalation aerosol is indicated for the treatment or prevention of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease.

1.2 Exercise-Induced Bronchospasm Albuterol sulfate inhalation aerosol is indicated for the prevention of exercise-induced bronchospasm in patients 4 years of age and older.

6 ADVERSE REACTIONS Use of albuterol sulfate may be associated with the following: • Paradoxical bronchospasm [see WARNINGS AND PRECAUTIONS ( 5.1 )] • Cardiovascular Effects [see WARNINGS AND PRECAUTIONS ( 5.4 )] • Immediate hypersensitivity reactions [see WARNINGS AND PRECAUTIONS ( 5.6 )] • Hypokalemia [see WARNINGS AND PRECAUTIONS ( 5.8 )] Most common adverse reactions (≥3.0% and >placebo) are headache, tachycardia, pain, dizziness, pharyngitis, and rhinitis.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc.

at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience A total of 1090 subjects were treated with albuterol sulfate inhalation aerosol, or with the same formulation of albuterol as in albuterol sulfate inhalation aerosol, during the worldwide clinical development program.

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.

Adult and Adolescents 12 Years of Age and Older The adverse reaction information presented in the table below concerning albuterol sulfate is derived from a 6-week, blinded study which compared albuterol sulfate inhalation aerosol (180 mcg four times daily) with a double-blinded matched placebo HFA-Inhalation Aerosol and an evaluator-blinded marketed active comparator HFA-134a albuterol inhaler in 172 asthmatic patients 12 to 76 years of age.

The table lists the incidence of all adverse events (whether considered by the investigator drug related or unrelated to drug) from this study which occurred at a rate of 3% or greater in the albuterol sulfate inhalation aerosol treatment group and more frequently in the albuterol sulfate inhalation aerosol treatment group than in the matched placebo group.

Overall, the incidence and nature of the adverse events reported for albuterol sulfate inhalation aerosol and the marketed active comparator HFA-134a albuterol inhaler were comparable.

Adverse Experience Incidences (% of Patients) in a Six-Week Clinical Trial This table includes all adverse events (whether considered by the investigator drug related or unrelated to drug) which occurred at an incidence rate of at least 3.0% in the albuterol sulfate inhalation aerosol group and more frequently in the albuterol sulfate inhalation aerosol group than in the placebo HFA Inhalation Aerosol group.

Body System/ Adverse Event (as Preferred Term) Albuterol Sulfate Inhalation Aerosol (N = 58) Marketed active comparator HFA-134a albuterol inhaler (N = 56) Matched Placebo HFA-134a Inhalation Aerosol (N = 58) Body as a Whole Headache 7 5 2 Cardiovascular Tachycardia 3 2 0 Musculoskeletal Pain 3 0 0 Nervous System Dizziness 3 0 0 Respiratory System Pharyngitis Rhinitis 14 5 7 4 9 2 Adverse events reported by less than 3% of the patients receiving albuterol sulfate inhalation aerosol but by a greater proportion of albuterol sulfate inhalation aerosol patients than the matched placebo patients, which have the potential to be related to albuterol sulfate inhalation aerosol, included chest pain, infection, diarrhea, glossitis, accidental injury (nervous system), anxiety, dyspnea, ear disorder, ear pain, and urinary tract infection.

In small cumulative dose studies, tremor, nervousness, and headache were the most frequently occurring adverse events.

Pediatric Patients 4 to 11 Years of Age Adverse events reported in a 3-week pediatric clinical trial comparing the same formulation of albuterol as in albuterol sulfate inhalation aerosol (180 mcg albuterol four times daily) to a matching placebo HFA inhalation aerosol occurred at a low incidence rate (no greater than 2% in the active treatment group) and were similar to those seen in adult and adolescent trials.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of albuterol sulfate inhalation aerosol.

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.

Reports have included rare cases of aggravated bronchospasm, lack of efficacy, asthma exacerbation (reported fatal in one case), muscle cramps, and various oropharyngeal side-effects such as throat irritation, altered taste, glossitis, tongue ulceration, and gagging.

The following adverse events have been observed in postapproval use of inhaled albuterol: urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles).

In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as: angina, hypertension or hypotension, palpitations, central nervous system stimulation, insomnia, headache, nervousness, tremor, muscle cramps, drying or irritation of the oropharynx, hypokalemia, hyperglycemia, and metabolic acidosis.