ALBUTEROL SULFATE

INDICATIONS AND USAGE Albuterol sulfate inhalation solution is indicated for the relief of bronchospasm in patients 2 years of age and older with reversible obstructive airway disease and acute attacks of bronchospasm.

DOSAGE AND ADMINISTRATION Adults and Children 2 to 12 Years of Age The usual dosage for adults and for children weighing at least 15 kg is 2.5 mg of albuterol (one vial) administered three to four times daily by nebulization. Children weighing <15 kg who require <2.5 mg/dose (i.e., less than a full vial) should use albuterol inhalation solution, 0.5% instead of albuterol inhalation solution, 0.083%. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, administer the entire contents of one sterile unit dose vial (3 mL of 0.083% inhalation solution) by nebulization. The flow rate is regulated to suit the particular nebulizer so that albuterol inhalation solution will be delivered over approximately 5 to 15 minutes. The use of albuterol sulfate inhalation solution can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimum benefit from regular use of the inhalation solution. If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately, as this is often a sign of seriously worsening asthma which would require reassessment of therapy.

CONTRAINDICATIONS Albuterol sulfate inhalation solution is contraindicated in patients with a history of hypersensitivity to any of its components.

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.

Drug Interactions Other sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol. Albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of albuterol on the vascular system may be potentiated. Beta-receptor blocking agents and albuterol inhibit the effect of each other.

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. * 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. ** In most cases of bronchospasm, this term was generally used to describe exacerbations in the underlying pulmonary disease. 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% Arrhythmias 0% 3% *Palpitation 0% 22% Respiratory ** 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% Postmarketing 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.

Pregnancy Teratogenic Effects Pregnancy Category C Albuterol has been shown to be teratogenic in mice when given subcutaneously in doses corresponding to 1.25 times the human nebulization dose (based on a 50 kg human). There are no adequate and well-controlled studies in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. A reproduction study in CD-1 mice with albuterol (0.025, 0.25, and 2.5 mg/kg subcutaneously, corresponding to 0.125, 1.25 and 12.5 times the maximum human nebulization dose, respectively) showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. None were observed at 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses treated with 2.5 mg/ kg isoproterenol (positive control). A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses at 50 mg/kg, corresponding to 250 times the maximum nebulization dose for a 50 kg human. During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between albuterol use and congenital anomalies has not been established.