ALBUTEROL SULFATE

Albuterol inhalation solution, USP is a sterile, clear, colorless solution of the sulfate salt of racemic albuterol, albuterol sulfate USP. Albuterol sulfate USP is a relatively selective beta 2 -adrenergic bronchodilator (see CLINICAL PHARMACOLOGY ). The chemical name for albuterol sulfate is α 1 -[( tert -Butylamino)methyl]-4-hydroxy- m -xylene-α,α'-diol sulfate (2:1) (salt), and its established chemical structure is as follows: The molecular weight of albuterol sulfate USP is 576.7 and the empirical formula is (C 13 H 21 NO 3 ) 2 • H 2 SO 4 . Albuterol sulfate USP is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization’s recommended name for albuterol is salbutamol. Albuterol inhalation solution, USP is supplied in two strengths in unit-dose vials. Each unit-dose vial contains either 0.75 mg of albuterol sulfate USP (equivalent to 0.021% or 0.63 mg of albuterol) or 1.5 mg of albuterol sulfate USP (equivalent to 0.042% or 1.25 mg of albuterol) with sodium chloride and sulfuric acid in a 3 mL isotonic, sterile, aqueous solution. Sodium chloride is added to adjust isotonicity of the solution and sulfuric acid is added to adjust pH of the solution to between 3 and 5 (see HOW SUPPLIED ). Albuterol inhalation solution, USP does not require dilution prior to administration by nebulization. For albuterol inhalation solution, USP like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari LC Plus™ nebulizer (with face mask or mouthpiece) connected to a Pari PRONEB™ compressor, under in vitro conditions, the mean delivered dose from the mouth piece (% nominal dose) was approximately 43% of albuterol (0.042% or 1.25 mg strength) and 39% of albuterol (0.021% or 0.63 mg strength) at a mean flow rate of 3.6 L/min. The mean nebulization time was 15 minutes or less. Albuterol inhalation solution, USP should be administered from a jet nebulizer at an adequate flow rate, via a mouthpiece or face mask (see DOSAGE AND ADMINISTRATION ). F:\daisy assignment\6月份\06.20\albuterol-sulfate-inhalation-solution-6-20-2008\figure-01.jpg

Albuterol inhalation solution is indicated for the relief of bronchospasm in patients 2 to 12 years of age with asthma (reversible obstructive airway disease).

The usual starting dosage for patients 2 to 12 years of age is 1.25 mg (0.042%) or 0.63 mg (0.021%) of albuterol inhalation solution administered 3 or 4 times daily, as needed, by nebulization. More frequent administration is not recommended. To administer 1.25 mg or 0.63 mg of albuterol, use the entire contents of one unit-dose vial (3 mL of 0.042% [1.25 mg] or 3 mL of 0.021% [0.63 mg] inhalation solution) by nebulization. Adjust nebulizer flow rate to deliver albuterol inhalation solution over 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. Patients 6 to 12 years of age with more severe asthma (baseline FEV 1 less than 60% predicted), weight > 40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose. Albuterol inhalation solution has not been studied in the setting of acute attacks of bronchospasm. A 2.5 mg dose of albuterol provided by a higher concentration product (2.5 mg albuterol per 3 mL) may be more appropriate for treating acute exacerbations, particularly in children 6 years old and above. 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. The drug compatibility (physical and chemical), clinical efficacy and safety of albuterol inhalation solution, when mixed with other drugs in a nebulizer have not been established. The safety and efficacy of albuterol inhalation solution have been established in clinical trials when administered using the Pari LC Plus™ nebulizer and Pari PRONEB™ compressor. The safety and efficacy of albuterol inhalation solution when administered with other nebulizer systems have not been established. Albuterol inhalation solution should be administered via jet nebulizer connected to an air compressor with adequate air flow, equipped with a mouthpiece or suitable face mask.

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

Clinical Trial Experience: Adverse events reported in >1% of patients receiving albuterol sulfate and more frequently than in patients receiving placebo in a four-week double-blind study are listed in the following table. Table 1: Adverse Events with an Incidence of >1% of Patients Receiving Albuterol Inhalation Solution and Greater than Placebo (expressed as % of treatment group) 1.25 mg (0.042%) Albuterol Inhalation Solution (n = 115) 0.63 mg (0.021%) Albuterol Inhalation Solution (n = 117) Placebo (n = 117) Asthma Exacerbation 13 11.1 8.5 Otitis Media 4.3 0.9 0 Allergic Reaction 0.9 3.4 1.7 Gastroenteritis 0.9 3.4 0.9 Cold Symptoms 0 3.4 1.7 Flu Syndrome 2.6 2.6 1.7 Lymphadenopathy 2.6 0.9 1.7 Skin/Appendage Infection 1.7 0 0 Urticaria 1.7 0.9 0 Migraine 0.9 1.7 0 Chest Pain 0.9 1.7 0 Bronchitis 0.9 1.7 0.9 Nausea 1.7 0.9 0.9 There was one case of ST segment depression in the 1.25 mg (0.042%) albuterol inhalation solution treatment group. No clinically relevant laboratory abnormalities related to albuterol inhalation solution administration were seen in this study. Postmarketing Experience: Metabolic acidosis has been reported after the use of albuterol inhalation solution. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure.

Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol inhalation solution. Albuterol inhalation solution should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or within 2 weeks of discontinuation of such agents, since the action of albuterol on the vascular system may be potentiated. Beta-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as albuterol inhalation solution, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances (e.g., prophylaxis after myocardial infarction), there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution. The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, caution is advised in the co-administration of beta-agonists with non-potassium sparing diuretics. Mean decreases of 16% to 22% in serum digoxin levels were demonstrated after single dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and albuterol.

Storage and Handling Store between 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light and excessive heat. Store unit-dose vials in protective foil pouch at all times. Once removed from the foil pouch, use vial within one week. Discard the vial if the solution is not colorless. Keep out of the reach of children. Rx Only Manufactured By: Nephron Pharmaceuticals Corporation West Columbia, SC 29172 STORING YOUR MEDICINE Store albuterol inhalation solution between 20°C to 25°C (68°F to 77°F) [ See USP Controlled Room Temperature]. Vials should be protected from light before use, therefore keep unused vials in the foil pouch. Once removed use within one week. Discard the vial if the solution is not colorless. Keep out of reach of children. Do not use after the expiration date printed on the vial.