Albuterol Sulfate Inhalation Solution, 0.5%

INDICATIONS AND USAGE Albuterol sulfate inhalation solution is indicated for the relief of bronchospasm in patients 12 years of age and older with reversible obstructive airway disease and acute attacks of bronchospasm.

DOSAGE AND ADMINISTRATION The usual dosage for adults and pediatric patients 12 years of age and older is 2.5 mg of albuterol (one unit-of-use vial) administered 3 to 4 times daily by nebulization. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, dilute 0.5 mL of the 0.5% solution for inhalation to a total volume of 3 mL with sterile normal saline solution and administer by nebulization. The flow rate is regulated to suit the particular nebulizer so that albuterol sulfate inhalation solution will be delivered over approximately 5 to 15 minutes. Drug compatibility (physical and chemical), efficacy, and safety of albuterol sulfate inhalation solution when mixed with other drugs in a nebulizer have not been established. The use of albuterol sulfate inhalation solution can be continued as medically indicated to control recurring bouts of bronchospasm. During treatment, most patients gain optimum benefit from regular use of the nebulizer solution. 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 nebulizer should be cleaned in accordance with the manufacturer’s instructions. Failure to do so could lead to bacterial contamination of the nebulizer and possible infection.

CONTRAINDICATIONS Albuterol sulfate inhalation solution is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.

WARNINGS 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 sulfate inhalation solution than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and 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. PARADOXICAL BRONCHOSPASM Albuterol sulfate inhalation solution can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol sulfate inhalation solution should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new vial. CARDIOVASCULAR EFFECTS Albuterol sulfate inhalation solution, 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 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 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. 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.

Drug Interactions Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol sulfate inhalation solution.

ADVERSE REACTIONS The results of clinical trials with albuterol sulfate inhalation solution in 135 patients showed the following side effects which were considered probably or possibly drug related: Percent Incidence of Adverse Reactions Reaction Percent Incidence (N=135) Central Nervous System Tremors 20 Dizziness 7 Nervousness 4 Headache 3 Insomnia 1 Gastrointestinal Nausea 4 Dyspepsia 1 Ear, nose and throat Nasal congestion 1 Pharyngitis <1 Cardiovascular Tachycardia 1 Hypertensions 1 Respiratory Bronchospasm 8 Cough 4 Bronchitis 4 Wheezing 1 No clinically relevant laboratory abnormalities related to albuterol sulfate inhalation solution were determined in these studies. Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles) have also been reported after the use of inhaled albuterol. To report SUSPECTED ADVERSE REACTIONS, contact Ritedose Pharmaceuticals, LLC at 1-855-806-3300 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Pregnancy Teratogenic Effects Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice at subcutaneous doses at and above 0.25 mg/kg (corresponding to less than the maximum recommended daily inhalation dose for adults on a mg/m 2 basis), induced cleft palate formation in 5 of 111 (4.5%) fetuses. At an subcutaneous dose of 2.5 mg/kg (approximately equal to the maximum recommended daily inhalation dose for adults on mg/m 2 basis), albuterol sulfate induced cleft palate formation in 10 of 108 (9.3%) fetuses. The drug did not induce cleft palate formation when administered at an subcutaneous dose of 0.025 mg/kg (corresponding to less than the maximum recommended daily inhalation dose for adults on mg/m 2 basis). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated with 2.5 mg/kg isoproterenol (positive control) admnistered subcutaneously. A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol was administered orally at a dose of 50 mg/kg dose (approximately 80 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis). Studies in pregnant rats with titrated Albuterol demonstrated that approximately 10% of the circulating maternal drug is transferred to the fetus. Disposition in the fetal lungs is comparable to maternal lungs; but fetal liver disposition is 1% of the maternal liver levels. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response. 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. No consistent pattern of defects can be discerned, and a relationship between albuterol use and congenital anomalies has not been established. Labor and Delivery Tocolysis: Because of the potential for beta-agonist interference with uterine contractility, use of albuterol sulfate inhalation solution for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. Albuterol has not been approved for the management of preterm labor. The benefit:risk ratio when albuterol is administered for tocolysis has not been established. Serious adverse reactions, including maternal pulmonary edema, have been reported during or following treatment of premature labor with beta 2 -agonists, including albuterol. Nursing Mothers It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness of albuterol inhalation solution and solution for inhalation in children below the age of 12 years have not been established.