red, although they should be administered with caution. 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 dose of the beta-agonist is exceeded. although the clinical significance of these effects is unknown, caution is advised in the co­-administration of beta-agonists with non-potassium sparing diuretics. 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.

tion solution than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration of the possible need for anti-inflammatory treatment (e.g., corticosteroids). fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs and with the home use of nebulizers. it is, therefore, essential that the physician instruct the patient in the need for further evaluation, if his/her asthma becomes worse. cardiovascular effects: albuterol sulfate inhalation solution, like 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 for albuterol sulfate inhalation solution at recommended doses, if they occur, the drug may need to be discontinued. in addition, beta-agonists have been reported to produce 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 sulfate inhalation solution like all other 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, and oropharyngeal edema.

en 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 plus tm nebulizer and pari proneb tm 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.

inically relevant laboratory abnormalities related to albuterol sulfate inhalation solution administration were seen in this study. postmarketing experience : metabolic acidosis has been reported after the use of albuterol sulfate inhalation solution. because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure.

red, although they should be administered with caution. 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 dose of the beta-agonist is exceeded. although the clinical significance of these effects is unknown, caution is advised in the co­-administration of beta-agonists with non-potassium sparing diuretics. 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.

fate was administered orally at 50 mg/kg (approximately 60 times the maximum recommended daily inhalation dose of albuterol sulfate inhalation solution on a mg/m 2 basis). a study in which pregnant rats were dosed with radiolabeled albuterol sulfate demonstrated that drug-related material was transferred from the maternal circulation to the fetus. there are no adequate and well-controlled studies of the use of albuterol sulfate in pregnant women. albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. during worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been reported in the offspring of patients being treated with albuterol. some of the mothers were taking multiple medications during their pregnancies. because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies has not been established.

ms, and/or electrocardiographic 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. pharmacokinetics: studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (ippb) or nebulizer administration; the remaining amount was recovered from the nebulizer and apparatus, and expired air. most of the absorbed dose was recovered in urine collected during the 24 hours after drug administration. following oral administration of 4 mg albuterol, the elimination half-life was five to six hours. following a 3 mg dose of nebulized albuterol in adults, the mean maximum albuterol plasma level at 0.5 hours was 2.1 ng/ml (range, 1.4 to 3.2 ng/ml). the pharmacokinetics of albuterol following administration of 0.63 mg or 1.25 mg albuterol sulfate inhalation solution by nebulization have not been determined in children 2 to 12 years old. animal pharmacology/toxicology: 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 plasma concentrations. in structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those found in 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. clinical trials: the safety and efficacy of albuterol sulfate inhalation solution was evaluated in a 4-week, multi­-center, randomized, double-blind, placebo-controlled, parallel group study in 349 children 6 to 12 years of age with mild-to-moderate asthma (mean baseline fev 1 60% to 70% of predicted). approximately half of the patients were also receiving inhaled corticosteroids. patients were randomized to receive albuterol sulfate inhalation solution 0.63 mg, albuterol sulfate inhalation solution 1.25 mg, or placebo three times a day administered via a pari lc plus tm nebulizer and a pari proneb tm compressor. racemic albuterol, delivered by a chlorofluorocarbon (cfc) metered dose inhaler (mdi) or nebulized, was used on an as-needed basis as the rescue medication. efficacy, as measured by the mean percent change from baseline in the area under the 6­-hour curve for fev 1 , was demonstrated for both active treatment regimens (n=112 [1.25 mg group] and n=110 [0.63 mg group]) compared with placebo (n=110) on day 1 and day 28. figures 1 and 2 illustrate the mean percentage change from pre-dose fev 1 on day 1 and day 28, respectively. the mean baseline fev 1 for all patients was 1.49 l. the onset of a 15% increase in fev 1 over baseline for both doses of albuterol sulfate inhalation solution was seen at 30 minutes (the first post-dose assessment). the mean time to peak effect was approximately 30 to 60 minutes for both doses on day 1 and after 4 weeks of treatment. the mean duration of effect, as measured by a >15% increase from baseline in fev 1 , was approximately 2.5 hours for both doses on day 1 and approximately 2 hours for both doses after 4 weeks of treatment. in some patients, the duration of effect was as long as 6 hours. figure 1 % change from pre-dose fev1 intent-to-treat population day 1 figure 2 % change from pre-dose fev1 intent-to-treat population day 28

on solution on a mg/m 2 basis). albuterol sulfate was not mutagenic in the ames test or a mutation test in yeast. albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an ah 1 strain mouse micronucleus assay. reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of albuterol sulfate up to 50 mg/kg (approximately 30 times the maximum recommended daily inhalation dose of albuterol sulfate inhalation solution on a mg/m 2 basis).

ndc 59651-184-05 5 such foil pouches in a carton (25 unit-dose vials) ndc 59651-184-25

. if the solution in the vial changes color or becomes cloudy, you should not use it. the drug compatibility (physical and chemical), clinical efficacy, and safety of albuterol sulfate inhalation solution, when mixed with other drugs in a nebulizer, has not been established. see illustrated patient's instructions for use.