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 the urine 24 hours after drug administration. Following a 3 mg dose of nebulized albuterol, the maximum albuterol plasma level at 0.5 hour was 2.1 ng/mL (range 1.4 to 3.2 ng/mL). There was a significant dose-related response in FEV 1and peak flow rate. It has been demonstrated that following oral administration of 4 mg of albuterol, the elimination half-life was 5 to 6 hours.

Paradoxical Bronchospasm:Albuterol inhalation solution can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol 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.

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 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 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  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 hours or chronically over several days or longer. If the patient needs more doses of albuterol 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.

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.

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.

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 in individual patients 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 pre-existing diabetes mellitus and ketoacidosis. As with other beta-agonist medications, 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 potassium supplementation.

Repeated dosing with 0.15 mg/kg of albuterol inhalation solution in children aged 5 to 17 years who were initially normokalemic has been associated with an asymptomatic decline of 20% to 25% in serum potassium levels.

Information for Patients: The action of albuterol inhalation solution may last up to 6 hours or longer. Albuterol inhalation solution should not be used more frequently than recommended. Do not increase the dose or frequency of albuterol inhalation solution without consulting your physician. If you find that treatment with albuterol inhalation solution becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately. While you are using albuterol inhalation solution, 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, tremor or nervousness. If you are pregnant or nursing, contact your physician about use of albuterol inhalation solution. Effective and safe use of albuterol  inhalation solution includes an understanding of the way that it should be administered.

Drug compatibility (physical and chemical), efficacy, and safety of albuterol  inhalation solution when mixed with other drugs in a nebulizer have not been established. See illustrated Patient's Instructions for Use.

Drug Interactions:Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.

Carcinogenesis, Mutagenesis, Impairment of Fertility:In a 2-year study in Sprague-Dawley rats, albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at e dietary doses of 2, 10, and 50 mg/kg (approximately 2, 8, and 40  times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m 2basis or approximately 3/5, 3, and 15 times, respectively, the maximum recommended daily inhalation dose in children on a mg/m 2basis). In another study this effect was blocked by the coadministration of propranolol, a nonselective 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/m 2basis or approximately 75 times the maximum recommended daily inhalation dose for children on a mg/m 2basis). In a 22-month study in the Golden hamster, albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg (approximately 25 times the maximum recommended daily inhalation dose for adults on a mg/m 2basis or approximately 10 times the maximum recommended daily inhalation dose for children on a mg/m 2basis).

Albuterol sulfate was not mutagenic in the Ames test with or without metabolic activation using tester strains S. typhimurium TA1537, TA1538, and TA98 or E. coliWP2, WP2uvrA, and WP67. No forward mutation was seen in yeast strain S. cerevisiaeS9 nor any mitotic gene conversion in yeast strain S. cerevisiae JD1 with or without metabolic activation. Fluctuation assays in S. typhimurium TA98 and E. coliWP2, both with metabolic activation, were negative. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at intraperitoneal doses of up to 200 mg/kg.

Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of albuterol sulfate up to 50 mg/kg (approximately 40 times the maximum recommended daily inhalation dose for adults on an mg/m 2basis).

Pregnancy

Labor and Delivery:Because of the potential for beta-agonist interference with uterine contractility, use of albuterol inhalation solution for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Tocolysis: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.

Storage and Handling

PROTECT FROM LIGHT. Store vials in pouch until time of use. Store between 20 °C to 25°C (68°F - 77°F), excursions permitted to 15 °C to 30 °C (59°F - 86°F) [see USP Controlled Room Temperature].

Rx Only

Distributed by:

Rising Pharma Holdings, Inc.

East Brunswick, NJ 08816

For Customer Service,

Call: 1-844-874-7464

IC 3028

Issued:02/2025

Manufactured By:
Nephron Pharmaceuticals Corporation
West Columbia, SC 29172

Patient's Instructions For Use

1. Twist open the top of one albuterol  inhalation solution unit-of-use container (Figure 1).

2. Squeeze the solution into the nebulizer reservoir through the appropriate opening (Figure 2).

3. Add 2.5 mL of diluting fluid – sterile normal saline solution (as your doctor has directed).

4. Gently swirl the nebulizer to mix the contents and connect it with the mouthpiece or face mask (Figure 3).

5. Connect the nebulizer to the compressor.

6.Sit in a comfortable, upright position; place the mouthpiece in your mouth (Figure 4) (or put on the face mask); and turn the compressor on.

7. Breathe as calmly, deeply and evenly as possible until no more mist is formed in the nebulizer chamber (about 5 to 15 minutes).  At this point, the treatment is finished.

8. Clean the nebulizer (see manufacturer’s instructions).  Failure to clean the nebulizer in accordance with the manufacturer’s instructions could lead to bacterial contamination of the nebulizer, and possible infection.

Note: Use only as directed by your physician. More frequent administration or higher doses are not recommended.