Albuterol Sulfate

INDICATIONS AND USAGE Albuterol sulfate inhalation solution is indicated for the relief of bronchospasm in patients 12 years of age and older with reversible obstructive airway disease and acute attacks of bronchospasm.

DOSAGE AND ADMINISTRATION 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 sulfate 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 sulfate inhalation solution over 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. 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 sulfate 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 sulfate inhalation solution, when mixed with other drugs in a nebulizer have not been established. The safety and efficacy of albuterol sulfate inhalation solution have been established in clinical trials when administered using the Pari LC PlusTM nebulizer and Pari PRONEBTM compressor. The safety and efficacy of albuterol sulfate inhalation solution when administered with other nebulizer systems have not been established. Albuterol sulfate 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.

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

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.

Drug Interactions Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects. Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol 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, because the action of albuterol on the vascular system may be potentiated. Beta-Blockers: Beta-adrenergic 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., as 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 could be considered, although they should be administered with caution. Diuretics: The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics. Digoxin: 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.

Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol 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, because the action of albuterol on the vascular system may be potentiated.

Beta-Blockers: Beta-adrenergic 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., as 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 could be considered, although they should be administered with caution.

Diuretics: The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics.

DESCRIPTION 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 PlusTM nebulizer (with face mask or mouthpiece) connected to a Pari PRONEBTM 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

OVERDOSAGE The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS , e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. In isolated cases in children 2 to 12 years of age, tachycardia with rates > 200 beats/min has been observed. As with all sympathomimetic l medications, cardiac arrest and even death may be associated with abuse of albuterol sulfate inhalation solution. Treatment consists of discontinuation of albuterol sulfate inhalation solution together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of albuterol sulfate inhalation solution. The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 810 times the maximum recommended daily inhalation dose for adults on an mg/ m 2 basis or approximately 300 times the maximum recommended daily inhalation dose for children on a mg/ m 2 basis). In mature rats, the subcutaneous (sc) median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately 365 times the maximum recommended daily inhalation dose for adults on an mg/ m 2 basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/ m 2 basis). In small young rats, the sc median lethal dose is approximately 2000 mg/kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/ m 2 basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/ m 2 basis). The inhalational median lethal dose has not been determined in animals.

HOW SUPPLIED Albuterol inhalation solution, USP is supplied as a 3 mL, clear, colorless, sterile, preservative-free, aqueous solution in two different strengths, 0.63 mg (0.021%) of albuterol (equivalent to 0.75 mg of albuterol sulfate in 3 mL) and 1.25 mg (0.042%) of albuterol (equivalent to 1.5 mg of albuterol sulfate in 3 mL) in unit-dose low-density polyethylene (LDPE) vials. Each unit-dose LDPE vial is protected in a foil pouch, and each foil pouch contains 1 unit-dose LDPE vial. Each strength of albuterol inhalation solution is available in a shelf carton containing multiple foil pouches. Albuterol inhalation solution, USP 0.021%* (0.63 mg* / 3 mL) (*potency expressed as albuterol) in unit-dose vials and is available in the following packaging configurations: NDC 64980-643-03 30 foil pouches, each containing 1 vial, total 30 vials per carton Albuterol inhalation solution, USP 0.042%* (1.25 mg* / 3 mL) (potency expressed as albuterol) in unit-dose vials and is available in the following packaging configurations: NDC 64980-644-02 25 foil pouches, each containing 1 vial, total 25 vials per carton NDC 64980-644-03 30 foil pouches, each containing 1 vial, total 30 vials per carton STORAGE: 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 Distributed by: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 For Customer Service, Call: 1-844-874-7464 Issued: 02/2025 IC 3032 Manufactured By: Nephron Pharmaceuticals Corporation West Columbia, SC 29172