Albuterol 2 mg Tablet, 500-count — NDC 69238-1344-5 (Billing 69238-1344-05)

WARNINGS Paradoxical Bronchospasm Albuterol tablets can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol tablets should be discontinued immediately and alternative therapy instituted. Deterioration of Asthma Asthma may deteriorate acutely over a period of hours, or chronically over several days or longer.

If the patient needs more doses of albuterol tablets than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids. Use of Anti-Inflammatory Agents The use of beta-adrenergic agonist bronchodilators alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids.

Cardiovascular Effects Albuterol tablets, like all other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of albuterol tablets at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.

The clinical significance of these findings is unknown. Therefore, albuterol tablets, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis and oropharyngeal edema.

Rarely, erythema multiforme and Stevens-Johnson syndrome have been associated with the administration of oral albuterol sulfate in children.

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.

PRECAUTIONS General Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen and could be expected to occur in some patients after use of any beta-adrenergic bronchodilator.

Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.

Information for Patients Patients being treated with albuterol tablets should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

The action of albuterol tablets may last up to 6 to 8 hours or longer. Albuterol tablets should not be taken more frequently than recommended. Do not increase the dose or frequency of albuterol tablets without consulting your physician.

If you find that treatment with albuterol tablets becomes less effective for symptomatic relief, your symptoms get worse, and/or you need to take the product more frequently than usual, you should seek medical attention immediately. While you are taking albuterol tablets, other inhaled drugs and asthma medications should be taken only as directed by your physician. Common adverse effects include palpitations, chest pain, rapid heart rate, and tremor or nervousness.

If you are pregnant or nursing, contact your physician about the use of albuterol tablets. Effective and safe use of albuterol tablets includes an understanding of the way that it should be administered. 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 rec… [Excerpted — this section continues on DailyMed.]