Albuterol - Albuterol tablet prescribing information
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.
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 co-administration is required, then alternative therapy should be considered.
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 non-potassium-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 co-administration 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, freely soluble in water and slightly soluble in ethanol. 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.
Each tablet also contains the following inactive ingredients: lactose monohydrate, magnesium stearate, pregelatinized (corn) starch and sodium lauryl sulfate.
CLINICAL PHARMACOLOGY
The primary action of beta-adrenergic agonist drugs, including albuterol, is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3',5'- adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP) in beta-adrenergic cells. The cyclic AMP thus formed mediates the cellular responses. Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta 2 -adrenergic receptors compared with isoproterenol. While it is recognized that beta 2 - adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta 2 -receptors in the human heart existing in a concentration between 10% and 50%. The precise function of these receptors has not been established.
In controlled clinical trials, albuterol has been shown to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects. Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or ECG changes.
Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol- O -methyl transferase.
Preclinical
Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.
Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.
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.
Clinical Trials
In controlled clinical trials in patients with asthma, the onset of improvement in pulmonary function, as measured by maximum midexpiratory flow rate (MMEF), was noted within 30 minutes after a dose of albuterol tablets, with peak improvement occurring between 2 and 3 hours. In controlled clinical trials in which measurements were conducted for 6 hours, significant clinical improvement in pulmonary function (defined as maintaining a 15% or more increase in FEV 1 and a 20% or more increase in MMEF over baseline values) was observed in 60% of patients at 4 hours and in 40% at 6 hours. In other single-dose, controlled clinical trials, clinically significant improvement was observed in at least 40% of the patients at 8 hours with the 4 mg albuterol tablet. No decrease in the effectiveness of albuterol tablets has been reported in patients who received long-term treatment with the drug in uncontrolled studies for periods up to 6 months.
In another controlled clinical study in asthmatic patients, it has been demonstrated that the initiation of therapy with either the 4 mg albuterol extended-release tablet dosed every 12 hours, or the 2 mg albuterol tablet dosed every 6 hours, achieve therapeutically comparable effects.
HOW SUPPLIED
Albuterol tablets, USP contain 2 mg or 4 mg of albuterol as 2.4 mg or 4.8 mg of albuterol sulfate, USP respectively.
Albuterol Tablets USP, 2 mg are supplied as white, round shaped, uncoated tablets, free from physical defects, debossed with “AA” and “91” on either side of score line and plain on other side.
They are available as follows:
Bottles of 100: NDC 69238-1344-1
Bottles of 500: NDC 69238-1344-5
Albuterol Tablets USP, 4 mg are supplied as white, round shaped, uncoated tablets, free from physical defects, debossed with “AA” and “90” on either side of score line and plain on other side.
They are available as follows:
Bottles of 100: NDC 69238-1345-1
Bottles of 500: NDC 69238-1345-5
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Protect from light.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep this and all drugs out of the reach of children.
Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Oral Solid Dosage Unit Ahmedabad 382213, INDIA
Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807
Rev. 10-2024-01
