ALBUTEROL SULFATE

Albuterol inhalation solution is a relatively selective beta 2 -adrenergic bronchodilator (see CLINICAL PHARMACOLOGY section below). Albuterol sulfate, the racemic form of albuterol, has the chemical name α 1 [( tert -Butylamino)methyl]-4-hydroxy- m -xylene-α,α´diol sulfate (2:1) (salt), and the following structural formula: Albuterol sulfate has a molecular weight of 576.71 and the molecular formula (C 13 H 21 NO 3 ) 2 •H 2 SO 4 . Albuterol sulfate is a white or practically white powder, freely soluble in water and slightly soluble in alcohol. The World Health Organization recommended name for albuterol base is salbutamol. Albuterol inhalation solution, USP 0.083% requires no dilution before administration. Each mL of albuterol inhalation solution, USP (0.083%) contains 0.83 mg of albuterol (as 1 mg of albuterol sulfate USP) in an isotonic, sterile, aqueous solution containing sodium chloride, edetate disodium and sodium citrate; hydrochloric acid is used to adjust the pH between 3 and 5. Albuterol inhalation solution, USP (0.083%) contains no sulfiting agents. Albuterol inhalation solution is a clear, colorless solution. albuterol-sulfate-chemical-structure

Albuterol 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.

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 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.

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

Clinical Trial Experience The results of clinical trials with albuterol 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 inhalation solution administration were determined in these studies. In comparing the adverse reactions reported for patients treated with albuterol 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% Arrhythmias 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% Postmarketing Experience Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, arrhythmias (including atrial fibrillations, supraventricular tachycardia, extrasystoles) and metabolic acidosis have been reported after the use of albuterol 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.

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 anti-depressants, since the action of albuterol on the vascular system may be potentiated. Beta-receptor blocking agents and albuterol inhibit the effect of each other.