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, USP are expressed in terms of albuterol base. 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 Respond 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.

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.

Pharmacokinetics Albuterol is rapidly and well absorbed following oral administration. In studies involving normal volunteers, the mean steady-state peak and trough plasm levels of albuterol were 6.7 ng/mL and 3.8 ng/mL, respectively, following dosing with a 2 mg albuterol tablet every 6 hours and 14.8 ng/mL and 8.6 ng/mL, respectively following dosing with a 4 mg albuterol tablet every 6 hours. Maximum albuterol plasma levels are usually obtained between 2 and 3 hours after dosing, and the elimination half-life is 5 to 6 hours. These data indicate that albuterol administered orally is dose proportional and exhibits dose independent pharmacokinetics. Albuterol extended-release tablets have been formulated to provide a duration of action of up to 12 hours. In studies conducted in normal volunteers, the mean steady-state peak and trough plasma levels of albuterol were 6.5 ng/mL and 3.0 ng/mL, respectively, following dosing with a 4 mg albuterol extended-release tablet every 12 hours. In addition, it has been shown that administration of a 4 mg albuterol extended-release tablets every 12 hours, and a 2 mg albuterol tablet every 6 hours for 5 days gave comparable peak albuterol levels and similar extent of absorption at steady state. In other studies, the analysis of urine samples of patients given tritiated albuterol (4 mg to 10 mg) orally showed that 65% to 90% of the dose was excreted over 3 days, with the majority of the dose being excreted within the first 24 hours. Sixty percent of this radioactivity was shown to be the metabolite. Feces collected over this period contained 4% of the administered dose.