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observed in children aged 5 to 11 years up to 6 hours after treatment with doses of 0.10 mg/kg or higher of albuterol inhalation solution. Patient’s Instructions for Use
Single doses of 3, 4, or 10 mg resulted in improvement in baseline PEFR that was comparable in extent and duration to a 2-mg dose, but doses above 3 mg were associated with heart rate increases of more than 10%. INDICATIONS AND USAGE
Albuterol Sulfate
Albuterol Sulfate Inhalation Solution is indicated for the relief of bronchospasm in patients 2 years of age and older with reversible Inhalation Solution, 0.083%*
obstructive airway disease and acute attacks of bronchospasm. CONTRAINDICATIONS
Albuterol Sulfate Inhalation Solution is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components. WARNINGS
Read complete instructions carefully
Paradoxical Bronchospasm: Albuterol Sulfate Inhalation Solution can
before using.
produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Albuterol Sulfate Inhalation Solution Albuterol Sulfate Inhalation
should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with Twist open the top of one Albuterol Sulfate Solution, 0.083%*
inhaled formulations, frequently occurs with the first use of a new canister or Inhalation Solution unit-of-use container and squeeze the entire contents into the nebulizer Cardiovascular Effects: Albuterol Sulfate Inhalation Solution, like all other
DESCRIPTION
beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or Albuterol Sulfate Inhalation Solution is a relatively selective beta2-adrenergic symptoms. Although such effects are uncommon after administration of bronchodilator (see CLINICAL PHARMACOLOGY). Albuterol sulfate, USP,
Albuterol Sulfate Inhalation Solution at recommended doses, if they occur, the racemic form of albuterol, has the chemical name α the drug may need to be discontinued. In addition, beta-agonists have been 1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-α,α′-diol sulfate (2:1) (salt) 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 Sulfate Inhalation Solution, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Deterioration of Asthma: Asthma may deteriorate acutely over a period of
Albuterol sulfate has a molecular weight of 576.71, and the molecular hours or chronically over several days or longer. If the patient needs more doses of Albuterol Sulfate Inhalation Solution than usual, this may be a 13H21NO3)2 • H2SO4. Albuterol sulfate is a white crystalline marker of destabilization of asthma and requires reevaluation of the patient powder, soluble in water and slightly soluble in ethanol. and treatment regimen, giving special consideration to the possible need for The World Health Organization recommended name for albuterol base is anti-inflammatory treatment, e.g., corticosteroids. Immediate Hypersensitivity Reactions: Immediate hypersensitivity
Albuterol Sulfate Inhalation Solution requires no dilution before reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and Each milliliter of Albuterol Sulfate Inhalation Solution contains 0.83 mg of albuterol (as 1 mg of albuterol sulfate) in an isotonic, sterile, aqueous Use of Anti-Inflammatory Agents: The use of beta-adrenergic agonist
solution containing sodium chloride; sulfuric acid is used to adjust the pH to bronchodilators alone may not be adequate to control asthma in many between 3 and 5. Albuterol Sulfate Inhalation Solution contains no sulfiting patients. Early consideration should be given to adding anti-inflammatory Albuterol Sulfate Inhalation Solution is a clear, colorless to light yellow PRECAUTIONS
General: Albuterol, as with all sympathomimetic amines, should be used
CLINICAL PHARMACOLOGY
with caution in patients with cardiovascular disorders, especially coronary In vitro studies and in vivo pharmacologic studies have demonstrated that insufficiency, cardiac arrhythmias, and hypertension; in patients with albuterol has a preferential effect on beta2-adrenergic receptors compared convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients with isoproterenol. While it is recognized that beta2-adrenergic receptors are who are unusually responsive to sympathomimetic amines. Clinically the predominant receptors in bronchial smooth muscle, data indicate that significant changes in systolic and diastolic blood pressure have been seen 10% to 50% of the beta-receptors in the human heart may be in individual patients and could be expected to occur in some patients after 2-receptors. The precise function of these receptors has not been use of any beta-adrenergic bronchodilator. Large doses of intravenous albuterol have been reported to aggravate Connect the nebulizer to the compressor. The pharmacologic effects of beta-adrenergic agonist drugs, including pre-existing diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol, are at least in part attributable to stimulation through beta- albuterol may produce significant hypokalemia in some patients, possibly adrenergic receptors of intracellular adenyl cyclase, the enzyme that through intracellular shunting, which has the potential to produce adverse catalyzes the conversion of adenosine triphosphate (ATP) to cardiovascular effects. The decrease is usually transient, not requiring Sit in a comfortable, upright position; place the cyclic-3′,5′-adenosine monophosphate (cyclic AMP). Increased cyclic AMP mouthpiece in your mouth (Figure 3)(or put on levels are associated with relaxation of bronchial smooth muscle and Repeated dosing with 0.15 mg/kg of albuterol inhalation solution in children the face mask); and turn on the compressor. inhibition of release of mediators of immediate hypersensitivity from cells, aged 5 to 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20% to 25% in serum potassium levels. Albuterol has been shown in most controlled clinical trials to have more Information For Patients: The action of Albuterol Sulfate Inhalation
effect on the respiratory tract, in the form of bronchial smooth muscle Solution may last up to 6 hours or longer. Albuterol Sulfate Inhalation relaxation, than isoproterenol at comparable doses while producing fewer Solution should not be used more frequently than recommended. Do not increase the dose or frequency of Albuterol Sulfate Inhalation Solution Controlled clinical studies and other clinical experience have shown that without consulting your physician. If you find that treatment with Albuterol inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a Sulfate Inhalation Solution becomes less effective for symptomatic relief, significant cardiovascular effect in some patients, as measured by pulse your symptoms become worse, and/or you need to use the product more rate, blood pressure, symptoms, and/or electrocardiographic changes. frequently than usual, you should seek medical attention immediately. Albuterol is longer acting than isoproterenol in most patients by any route of While you are using Albuterol Sulfate Inhalation Solution, other inhaled drugs administration because it is not a substrate for the cellular uptake processes and asthma medications should be taken only as directed by your physician. for catecholamines nor for catechol-O-methyl transferase. Common adverse effects include palpitations, chest pain, rapid heart rate, and tremor or nervousness. If you are pregnant or nursing, contact your Pharmacokinetics: Studies in asthmatic patients have shown that less than
physician about use of Albuterol Sulfate Inhalation Solution. Effective and 20% of a single albuterol dose was absorbed following either safe use of Albuterol Sulfate Inhalation Solution includes an understanding IPPB (intermittent positive-pressure breathing) or nebulizer administration; of the way that it should be administered. the remaining amount was recovered from the nebulizer and apparatus and expired air. Most of the absorbed dose was recovered in the urine 24 hours Drug compatibility (physical and chemical), efficacy, and safety of Albuterol after drug administration. Following a 3-mg dose of nebulized albuterol in Sulfate Inhalation Solution when mixed with other drugs in a nebulizer have adults, the maximum albuterol plasma levels at 0.5 hours were 2.1 ng/mL (range, 1.4 to 3.2 ng/mL). There was a significant dose-related response in See illustrated Patient's Instructions for Use. FEV1 (forced expiratory volume in one second) and peak flow rate. It has Drug Interactions: Other short-acting sympathomimetic aerosol
been demonstrated that following oral administration of 4 mg of albuterol, the Breathe as calmly, deeply and evenly as
bronchodilators or epinephrine should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, possible until no more mist is formed in the Preclinical: Intravenous studies in rats with albuterol sulfate have
they should be used with caution to avoid deleterious cardiovascular effects. nebulizer chamber (about 5 to 15 minutes). At demonstrated that albuterol crosses the blood-brain barrier and reaches Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol
brain concentrations amounting to approximately 5.0% of the plasma should be administered with extreme caution to patients being treated with concentrations. In structures outside the brain barrier (pineal and pituitary monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks glands), albuterol concentrations were found to be 100 times those in the of discontinuation of such agents, because the action of albuterol on the Studies in laboratory animals (minipigs, rodents, and dogs) have Clean the nebulizer (see manufacturer’s Beta-Blockers: Beta-adrenergic receptor blocking agents not only block the
demonstrated the occurrence of cardiac arrhythmias and sudden death (with pulmonary effect of beta-agonists, such as Albuterol Sulfate Inhalation histologic evidence of myocardial necrosis) when beta-agonists and Solution, but may produce severe bronchospasm in asthmatic patients. methylxanthines were administered concurrently. The clinical significance of Therefore, patients with asthma should not normally be treated with beta- blockers. However, under certain circumstances, e.g., as prophylaxis after Clinical Trials: In controlled clinical trials in adults, most patients exhibited
myocardial infarction, there may be no acceptable alternatives to the use of an onset of improvement in pulmonary function within 5 minutes as beta-adrenergic blocking agents in patients with asthma. In this setting, determined by FEV1. FEV1 measurements also showed that the maximum cardioselective beta-blockers could be considered, although they should be average improvement in pulmonary function usually occurred at approximately 1 hour following inhalation of 2.5 mg of albuterol by compressor-nebulizer and remained close to peak for 2 hours. Clinically significant improvement in pulmonary function (defined as maintenance of a 1 over baseline values) continued for 3 to 4 hours in most patients, with some patients continuing up to 6 hours. Published reports of trials in asthmatic children aged 3 years or older have demonstrated significant improvement in either FEV within 2 to 20 minutes following single doses of albuterol inhalation solution. An increase of 15% or more in baseline FEV1 has been Note: Use only as directed by your doctor. More
Diuretics: The ECG changes and/or hypokalemia that may result from the
ADVERSE REACTIONS
frequent administration or higher doses are not
administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the The results of clinical trials with Albuterol Sulfate Inhalation Solution, recommended.
recommended dose of the beta-agonist is exceeded. Although the clinical 0.5% in 135 patients showed the following side effects that were considered probably or possibly drug related: significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics. The safety and effectiveness of Albuterol Sulfate Inhalation Percent Incidence of Adverse Reactions
Digoxin: Mean decreases of 16% to 22% in serum digoxin levels were
Solution have not been determined when one or more demonstrated after single-dose intravenous and oral administration of drugs are mixed with it in a nebulizer. Check with your albuterol, respectively, to normal volunteers who had received digoxin for Central Nervous System
doctor before mixing any medications in your nebulizer. 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 Protect from light. Store between 2° and 25° C (36° and
77° F). Discard if solution becomes discolored. (Note:
Gastrointestinal
Carcinogenesis, Mutagenesis, Impairment of Fertility: In a 2-year study
Albuterol Sulfate Inhalation Solution is a clear,
in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related colorless to light yellow solution.)
increase in the incidence of benign leiomyomas of the mesovarium at dietary Ear, nose, and throat
doses of 2.0, 10, and 50 mg/kg (approximately 2, 8, and 40 times, respectively, the maximum recommended daily inhalation dose for adults on Cardiovascular
a mg/m2 basis, or, approximately 3/5, 3, and 15 times, respectively, the maximum recommended daily inhalation dose in children on a mg/m2 basis). In another study this effect was blocked by the coadministration of Respiratory
propranolol, a non-selective beta-adrenergic antagonist. In an 18-month study in CD-1 mice albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg (approximately 200 times the maximum recommended daily inhalation dose for adults on a mg/m2 basis, or, approximately 75 times the maximum recommended daily inhalation dose No clinically relevant laboratory abnormalities related to Albuterol Sulfate Inhalation for children on a mg/m2 basis). In a 22-month study in the Golden hamster Solution administration were determined in these studies. albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up Rare cases of supraventricular tachycardia, urticaria, angioedema, rash, bronchospasm, and to 50 mg/kg (approximately 25 times the maximum recommended daily oropharyngeal edema have been reported after the use of inhaled albuterol. inhalation dose for adults on a mg/m2 basis, or, approximately 10 times the OVERDOSAGE
maximum recommended daily inhalation dose for children on a mg/m2 The expected symptoms with overdosage are those of excessive beta- basis). Albuterol sulfate was not mutagenic in the Ames test with or without adrenergic stimulation and/or occurrence or exaggeration of any of the metabolic activation using tester strains S. typhimurium TA1537, TA1538, symptoms listed under ADVERSE REACTIONS, e.g., seizures, angina, and TA98 or E. coli WP2, WP2uvrA, and WP67. No forward mutation was hypertension or hypotension, tachycardia with rates up to 200 beats per seen in yeast strain S. cerevisiae S9 nor any mitotic gene conversion in minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, yeast strain S. cerevisiae JD1 with or without metabolic activation. nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may Fluctuation assays in S. typhimurium TA98 and E. coli WP2, both with also occur. In isolated cases in children 2 to 12 years of age, tachycardia metabolic activation, were negative. Albuterol sulfate was not clastogenic in with rates >200 beats/min has been observed. a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at intraperitoneal doses of up to 200 mg/kg. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Albuterol Sulfate Inhalation Solution. Reproduction studies in rats demonstrated no evidence of impaired fertility at Treatment consists of discontinuation of Albuterol Sulfate Inhalation Solution oral doses up to 50 mg/kg (approximately 40 times the maximum together with appropriate symptomatic therapy. The judicious use of a recommended daily inhalation dose for adults on a mg/m2 basis). cardioselective beta-receptor blocker may be considered, bearing in mind Pregnancy: Teratogenic Effects: Pregnancy Category C: Albuterol has
that such medication can produce bronchospasm. There is insufficient been shown to be teratogenic in mice. A study in CD-1 mice at evidence to determine if dialysis is beneficial for overdosage of Albuterol subcutaneous (sc) doses of 0.025, 0.25, and 2.5 mg/kg (approximately 1/100, 1/10, and 1.0 times, respectively, the maximum recommended daily The oral median lethal dose of albuterol sulfate in mice is greater than 2000 inhalation dose for adults on a mg/m2 basis), showed cleft palate formation in mg/kg (approximately 810 times the maximum recommended daily 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 inhalation dose for adults on a mg/m2 basis, or, approximately 300 times the mg/kg. The drug did not induce cleft palate formation at the lowest dose, maximum recommended daily inhalation dose for children on a mg/m2 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses from basis). In mature rats, the subcutaneous (sc) median lethal dose of albuterol females treated with 2.5 mg/kg isoproterenol (positive control) sulfate is approximately 450 mg/kg (approximately 365 times the maximum subcutaneously, (approximately 1.0 times the maximum recommended daily recommended daily inhalation dose for adults on a mg/m2 basis, or, inhalation dose for adults on a mg/m2 basis). approximately 135 times the maximum recommended daily inhalation dose A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of for children on a mg/m2 basis). In small young rats, the sc median lethal 19 (37%) fetuses when albuterol was administered orally at a 50 mg/kg dose is approximately 2000 mg/kg (approximately 1600 times the maximum dose (approximately 80 times the maximum recommended daily inhalation recommended daily inhalation dose for adults on a mg/m2 basis, or, approximately 600 times the maximum recommended daily inhalation dose There are no adequate and well-controlled studies in pregnant women. for children on a mg/m2 basis). The inhalational median lethal dose has not Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. DOSAGE AND ADMINISTRATION
During worldwide marketing experience, various congenital anomalies, Adults and Children 2 to 12 Years of Age: The usual dosage for adults
including cleft palate and limb defects, have been rarely reported in the and for children weighing at least 15 kg is 2.5 mg of albuterol (one unit dose offspring of patients being treated with albuterol. Some of the mothers were vial) administered three to four times daily by nebulization. Children taking multiple medications during their pregnancies. No consistent pattern weighing less than 15 kg who require less than 2.5 mg/dose (i.e., less than a of defects can be discerned, and a relationship between albuterol use and full unit dose vial) should use Albuterol Sulfate Inhalation Solution, 0.5% congenital anomalies has not been established. instead of Albuterol Sulfate Inhalation Solution, 0.083%. More frequent Use in Labor and Delivery: Because of the potential for beta-agonist
administration or higher doses are not recommended. To administer 2.5 mg interference with uterine contractility, use of Albuterol Sulfate Inhalation of albuterol, administer the entire contents of one sterile unit dose vial (3 mL Solution for relief of bronchospasm during labor should be restricted to those of 0.083% inhalation solution) by nebulization. The flow rate is regulated to patients in whom the benefits clearly outweigh the risk. suit the particular nebulizer so that Albuterol Sulfate Inhalation Solution will Tocolysis: Albuterol has not been approved for the management of
be delivered over approximately 5 to 15 minutes. preterm labor. The benefit:risk ratio when albuterol is administered for The use of Albuterol Sulfate Inhalation Solution can be continued as medically indicated to control recurring bouts of bronchospasm. During this tocolysis has not been established. Serious adverse reactions, including maternal pulmonary edema, have been reported during or following time most patients gain optimal benefit from regular use of the inhalation Nursing Mothers: It is not known whether this drug is excreted in human
If a previously effective dosage regimen fails to provide the usual relief, milk. Because of the potential for tumorigenicity shown for albuterol in some medical advice should be sought immediately as this is often a sign of animal studies, a decision should be made whether to discontinue nursing or seriously worsening asthma that would require reassessment of therapy. to discontinue the drug, taking into account the importance of the drug to the Drug compatibility (physical and chemical), efficacy, and safety of Albuterol Sulfate Inhalation Solution when mixed with other drugs in a nebulizer have Pediatric Use: The safety and effectiveness of Albuterol Sulfate Inhalation
Solution have been established in children 2 years of age or older. Use of HOW SUPPLIED
Albuterol Sulfate Inhalation Solution in these age-groups is supported by evidence from adequate and well-controlled studies of Albuterol Sulfate Albuterol Sulfate Inhalation Solution, 0.083% is contained in plastic sterile unit dose vials of 3 mL each, supplied in foil pouches: Inhalation Solution in adults; the likelihood that the disease course, pathophysiology, and the drug's effect in pediatric and adult patients are substantially similar; and published reports of trials in pediatric patients 3 years of age or older. The recommended dose for the pediatric population is based upon three published dose comparison studies of efficacy and safety NDC 0487-9501-01 30 vials, each in an individual foil pouch. in children 5 to 17 years, and on the safety profile in both adults and pediatric NDC 0487-9501-02 30 vials, each in an individual foil pouch, robot ready. patients at doses equal to or higher than the recommended doses. The Protect from light. Store between 2° and 25° C (36° and 77° F). Discard
safety and effectiveness of Albuterol Sulfate Inhalation Solution in children if solution becomes discolored. (Note: Albuterol Sulfate Inhalation
below 2 years of age have not been established. Solution is a clear, colorless to light yellow solution.)

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