Albuterol Sulfate

WARNINGS As with other inhaled beta-adrenergic agonists, albuterol sulfate inhalation solution can produce paradoxical bronchospasm, which can be life threatening. If it occurs, the preparation should be discontinued immediately and alternative therapy instituted. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs and with the home use of nebulizers. It is, therefore, essential that the physician instruct the patient in the need for further evaluation, if his/her asthma becomes worse. In individual patients, any beta 2 -adrenergic agonist, including albuterol solution for inhalation, may have a clinically significant cardiac effect. Immediate hypersensitivity reactions may occur after administration of albuterol as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

ADVERSE REACTIONS Clinical Trial Experience The results of clinical trials with albuterol sulfate inhalation solution in 135 patients showed the following side effects which were considered probably or possibly drug related: Central Nervous System: tremors (20%), dizziness (7%), nervousness (4%), headache (3%), insomnia (1%). Gastrointestinal: nausea (4%), dyspepsia (1%). Ear, Nose and Throat: pharyngitis (<1%), nasal congestion (1%). Cardiovascular: tachycardia (1%), hypertension (1%). Respiratory: bronchospasm (8%), cough (4%), bronchitis (4%), wheezing (1%). No clinically relevant laboratory abnormalities related to albuterol sulfate inhalation solution administration were determined in these studies. In comparing the adverse reactions reported for patients treated with albuterol sulfate inhalation solution with those of patients treated with isoproterenol during clinical trials of three months, the following moderate to severe reactions, as judged by the investigators, were reported. This table does not include mild reactions. Percent Incidence of Moderate to Severe Adverse Reactions Reaction Albuterol N=65 Isoproterenol N=65 Central Nervous System Tremors 10.7% 13.8% Headache 3.1% 1.5% Insomnia 3.1% 1.5% Cardiovascular Hypertension 3.1% 3.1% Arrythmias 0% 3% The finding of no arrhythmias and no palpitations after albuterol administration in this clinical study should not be interpreted as indicating that these adverse effects cannot occur after the administration of inhaled albuterol. Palpitation 0% 22% Respiratory In most cases of bronchospasm, this term was generally used to describe exacerbations in the underlying pulmonary disease. Bronchospasm 15.4% 18% Cough 3.1% 5% Bronchitis 1.5% 5% Wheeze 1.5% 1.5% Sputum Increase 1.5% 1.5% Dyspnea 1.5% 1.5% Gastrointestinal Nausea 3.1% 0% Dyspepsia 1.5% 0% Systemic Malaise 1.5% 0% Post-Marketing Experience Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillations, supraventricular tachycardia, extrasystoles) and metabolic acidosis have been reported after the use of albuterol sulfate inhalation solution. 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.

<table width="75%"><caption>Percent Incidence of Moderate to Severe Adverse Reactions</caption><thead><tr><th styleCode="Lrule Rrule">Reaction</th><th styleCode="Rrule">Albuterol N=65 </th><th styleCode="Rrule">Isoproterenol N=65 </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Central Nervous System</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Tremors</td><td styleCode="Rrule">10.7%</td><td styleCode="Rrule">13.8%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">3.1%</td><td styleCode="Rrule">1.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Insomnia</td><td styleCode="Rrule">3.1%</td><td styleCode="Rrule">1.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Cardiovascular</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hypertension</td><td styleCode="Rrule">3.1%</td><td styleCode="Rrule">3.1%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Arrythmias</td><td styleCode="Rrule">0%</td><td styleCode="Rrule">3%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><footnote ID="K1034">The finding of no arrhythmias and no palpitations after albuterol administration in this clinical study should not be interpreted as indicating that these adverse effects cannot occur after the administration of inhaled albuterol.</footnote>Palpitation </td><td styleCode="Rrule">0%</td><td styleCode="Rrule">22%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Respiratory</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><footnote ID="K1058">In most cases of bronchospasm, this term was generally used to describe exacerbations in the underlying pulmonary disease.</footnote>Bronchospasm </td><td styleCode="Rrule">15.4%</td><td styleCode="Rrule">18%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Cough</td><td styleCode="Rrule">3.1%</td><td styleCode="Rrule">5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Bronchitis</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Wheeze</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">1.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Sputum Increase</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">1.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dyspnea</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">1.5%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Nausea</td><td styleCode="Rrule">3.1%</td><td styleCode="Rrule">0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dyspepsia</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">0%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Systemic</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule">Malaise</td><td styleCode="Rrule">1.5%</td><td styleCode="Rrule">0%</td></tr></tbody></table>