Albuterol

INDICATIONS AND USAGE Albuterol tablets, USP are indicated for the relief of bronchospasm in adults and children 6 years of age and older with reversible obstructive airway disease.

DOSAGE AND ADMINISTRATION The following dosages of albuterol tablets are expressed in terms of albuterol base. Albuterol tablets Usual Dosage Pediatric Patients 6 to 12 Years of Age: For pediatric patients 6 to 12 years of age, the usual dosage is 2 mg three or four times a day. Adults and Pediatric Patients Over 12 Years of Age: For adults and pediatric patients over 12 years of age, the usual starting dosage is 2 or 4 mg three or four times a day. Dosage Adjustment Pediatric Patients 6 to 12 Years of Age Who Fail to Res pond to the Initial Starting Dosage of 2 mg Four Times a Day: For pediatric patients from 6 to 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day, the dosage may be cautiously increased stepwise, but not to exceed 24 mg/day (given in divided doses). Adults and Pediatric Patients Over 12 Years of Age: For adults and pediatric patients over 12 years of age, a dosage above 4 mg four times a day should be used only when the patient fails to respond to lower dose. The dosage should be cautiously increased stepwise up to a maximum of 8 mg four times a day as tolerated if a favorable response does not occur with the 4 mg initial dosage. Elderly Patients and Those Sensitive to Beta-adrenergic Stimulators: An initial dosage of 2 mg three or four times a day is recommended for elderly patients and for those with a history of unusual sensitivity to beta-adrenergic stimulators. If adequate bronchodilation is not obtained, dosage may be increased gradually as tolerated to as much as 8 mg three or four times a day. The total daily dose should not exceed 24 mg per day in pediatric patients from 6 to 12 years of age and 32 mg in adults and pediatric patients over 12 years of age.

CONTRAINDICATIONS Albuterol tablets are contraindicated in patients with a history of hypersensitivity to albuterol, or any of their components.

ADVERSE REACTIONS The adverse reactions to albuterol are similar in nature to those of other sympathomimetic agents. Albuterol Tablets Adverse Experience Incidence (% of patients) in Adults and Children 6 Years of Age and Older Adverse Event Percent Incidence Central nervous system Nervousness 20 Tremor 20 Headache 7 Dizziness 2 Weakness 2 Sleeplessness 2 Irritability < 1 Drowsiness < 1 Restlessness < 1 Cardiovascular Palpitations 5 Tachycardia 5 Flushing < 1 Chest discomfort < 1 Musculoskeletal Muscle cramps 3 Gastrointestinal Nausea 2 Genitourinary Difficulty in micturition < 1 Albuterol Extended-release Tablets Incidence of Adverse Reactions (% of Patients) in a 1-week Clinical Trials* Adverse Event Albuterol Extended-release Tablets (4 mg every 12 hours) Albuterol Tablets (2 mg every 6 hours) Nausea 4 4 Nervousness 2 6 Vomiting 2 4 Somnolence 2 2 *This table includes adverse reactions considered to be possibly or probably treatment related in 1-week clinical trial comparing a 4 mg albuterol extended-release tablet administered every 12 hours to a 2 mg albuterol tablet administered every 6 hours. Although not reported for albuterol extended-release tablets in the above study, there have been reports of tremor in other trials. When all clinical experience is considered, the incidence of tremor is approximately the same as that seen with albuterol tablets. A placebo-controlled trial of 4 weeks duration in 157 mild-to-moderate asthmatic children aged 6 to 12 years, demonstrated the safety of escalating doses of albuterol extended-release tablets. In this study, the starting dose of albuterol extended-release tablets was 4 mg twice daily. Patients were advanced to a maximum of 12 mg albuterol extended-release tablets twice daily by the investigator, based on patient tolerance and response. Only one of the 79 children treated with albuterol extended-release tablets was advanced to the maximum daily dose of 12 mg twice daily. The following treatment-related adverse events occurred in more than 5% of treated patients and were greater in albuterol extended-release tablets patients when compared to placebo: Incidence of Adverse Events (% of Patients) in a 4-Week Placebo-Controlled Trial in 157 Children 6 to 12 Years of Age Adverse Event Albuterol Extended-release Tablets % Placebo % Headache 22 9 Nervousness 13 6 Insomnia 11 5 Tremor 10 1 Palpitation 8 1 Tachycardia 8 1 Other adverse events were noted in 5% or fewer patients, or had equal or greater rates of occurrence in placebo patients than in albuterol extended-release tablets patients. Cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal edema and arrhytmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles) have been reported after the use of albuterol tablets. In addition to those adverse reactions reported above, albuterol, like other sympathomimetic agents, can cause adverse reactions such as angina, central nervous system stimulation, drying or irritation of the oropharynx, hypertension, unusual taste, and vertigo. The reactions are generally transient in nature, and it is usually not necessary to discontinue treatment with albuterol tablets. In selected cases, however, dosage may be reduced temporarily; after the reaction has subsided, dosage should be increased in small increments to the optimal dosage. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions The concomitant use of albuterol tablets and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving albuterol tablets. Such concomitant use, however, should be individualized and not given on a routine basis. If regular coadministration is required, then alternative therapy should be considered. 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 tablets, 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.

DESCRIPTION Albuterol tablets, USP contain albuterol sulfate, USP, the racemic form of albuterol and a relatively selective beta 2 -adrenergic bronchodilator. Albuterol sulfate 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: The molecular weight of albuterol sulfate is 576.71, and the molecular formula is (C 13 H 21 NO 3 ) 2 •H 2 SO 4 . Albuterol sulfate, USP is a white or practically white powder. It is freely soluble in water, slightly soluble in alcohol, in chloroform and in ether. The World Health Organization recommended name for albuterol base is salbutamol. Each albuterol tablet, USP for oral administration contains 2 mg or 4 mg of albuterol as 2.4 mg or 4.8 mg of albuterol sulfate, USP respectively and following inactive ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch (botanical source: maize) and sodium starch glycolate. FDA approved dissolution specification differs from the USP dissolution specification. Albuterol Tablet

OVERDOSAGE The expected symptoms with overdosage are those of excessive bet a -adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS , e.g., angina, hypertension tachycardia with rates up to 200 beats per minute, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness and insomnia. In addition, seizures, hypotension, arrhythmias, fatigue, malaise and hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Albuterol tablets. Treatment consists of discontinuation of Albuterol tablets together with appropriate symptomatic therapy. The judicious use of a cardioselective bet a -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 tablets. The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 250 times the maximum recommended daily oral dose for adults on an mg/ m 2 basis, and approximately 200 times the maximum recommended daily oral dose for children on an mg/ m 2 basis). In mature rats, the subcutaneous (sc) median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately 110 times the maximum recommended daily oral dose for adults on an mg/ m 2 basis, and approximately 90 times the maximum recommended daily oral dose for children on an mg/ m 2 basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/kg (approximately 510 times the maximum recommended daily oral dose for adults on an mg/ m 2 basis, and approximately 400 times the maximum recommended daily oral dose for children on an mg/ m 2 basis).

HOW SUPPLIED Each Albuterol tablet, USP for oral administration contains 2 mg or 4 mg albuterol as 2.4 mg or 4.8 mg of albuterol sulfate, USP respectively. Albuterol Tablets, USP containing 2 mg albuterol as the sulfate are white, round shaped, scored tablets debossed with “AC 2” on one side and plain on other side. They are available as follows: NDC 71205-898-30 Bottles of 30 tablets NDC 71205-898-60 Bottles of 60 tablets NDC 71205-898-90 Bottles of 90 tablets NDC 71205-898-00 Bottles of 100 tablets NDC 71205-898-55 Bottles of 500 tablets NDC 71205-898-11 Bottles of 1000 tablets Albuterol Tablets, USP containing 4 mg albuterol as the sulfate are white, round shaped, scored tablets debossed with “AC 4” on one side and plain on other side. They are available as follows: NDC 71205-899-30 Bottles of 30 tablets NDC 71205-899-60 Bottles of 60 tablets NDC 71205-899-90 Bottles of 90 tablets NDC 71205-899-00 Bottles of 100 tablets NDC 71205-899-55 Bottles of 500 tablets NDC 71205-899-11 Bottles of 1000 tablets Store Albuterol tablets at 20° to 25°C (68° to 77°F). [See USP for controlled Room Temperature.] Protect from light Manufactured by Appco Pharma LLC. Piscataway, New Jersey 08854 Distributed by: Rising Pharmaceuticals, Inc. Saddle Brook, NJ 07663 Repackaged and Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320 Revised: 01/2019 Store Albuterol tablets at 20° to 25°C (68° to 77°F). [See USP for controlled Room Temperature.] Protect from light Manufactured by Appco Pharma LLC. Piscataway, New Jersey 08854 Distributed by: Rising Pharmaceuticals, Inc. Saddle Brook, NJ 07663 Repackaged and Relabeled by: Proficient Rx LP Thousand Oaks, CA 91320 Revised: 01/2019