Albuterol Sulfate Inhalation Solution

0.5%2.5 mg* / 0.5 mL

(*Equivalent to 3 mg of albuterol sulfate)

*Potency expressed as albuterol

Albuterol Sulfate Inhalation Solution, 0.5% contains albuterol sulfate, USP, the racemic form of albuterol and a relatively selective beta 2- adrenergic bronchodilator. Albuterol sulfate has the chemical name α 1[(tert-Butylamino) methyl]-4-hydroxy-m-xylene-α, α’-diol sulfate (2:1) (salt), and the following chemical structure:

The molecular weight of albuterol sulfate is 576.7, and the empirical formula is (C 13H 21NO 3) 2• H 2SO 4. Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization’s recommended name for albuterol base is salbutamol.

Albuterol sulfate inhalation solution, 0.5%, is in concentrated form. Dilute 0.5 mL of the solution to 3 mL with sterile normal saline solution prior to administration by nebulization.

Each 0.5 mL Unit-Dose Vial Contains:2.5 mg of albuterol (equivalent to 3 mg of albuterol sulfate, USP) in a sterile, aqueous solution; sulfuric acid is used to adjust the pH to between 3 and 5. Albuterol Sulfate Inhalation solution contains no sulfiting agents or preservatives. It is supplied in 0.5 mL sterile Unit-Dose Vials.

Albuterol sulfate inhalation solution is a clear, colorless to light yellow solution.

The primary action of beta-adrenergic drugs, is to stimulate adenyl cyclase, the enzyme that catalyzes the formation of cyclic-3' ,5'-adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP) in beta-adrenergic cells. The cyclic AMP thus fanned mediates the cellular responses. Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

​ In vitrostudies and in vivopharmacologic studies have demonstrated that albuterol has a preferential effect on beta 2-adrenergic receptors compared with isoproterenol. While it is recognized that beta 2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta 2-receptors in the human heart existing in a concentration between 10% and 50%. The precise function of these receptors has not been established.

In controlled clinical trials, albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.

Controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or ECG 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.

The effects of rising doses of albuterol and isoproterenol areosols were studied in volunteers and asthmatic patients. Results in normal volunteers indicated that the propensity for increase in heart rate for albuterol is 1/2 to 1/4 that of isoproterenol. In asthmatic patients similar cardiovascular differentiation between the MO drugs was also seen.

In controlled clinical trials, most patients exhibited an onset of improvement in pulmonary function within 5 minutes as determined by FEV 1. FEV 1measurements also showed that the maximum 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 15% or more increase in FEV 1over baseline values) continued for 3 to 4 hours in most patients and in some patients continued up to 6 hours.

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.

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

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.

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:

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.

The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS, e.g., angina, hypertension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, malaise, and insomnia. In addition, seizures, hypotension, fatigue, and hypokalemia may also occur. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of albuterol sulfate inhalation solution. Treatment consists of discontinuation of albuterol sulfate inhalation solution together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of albuterol sulfate inhalation solution.

The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 810 times the maximum recommended daily inhalation dose for adults on a mg/m 2basis). In mature rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately 360 times the maximum recommended daily inhalation dose for adults on a mg/m 2basis). In small young rats, the subcutaneous median lethal dose of albuterol sulfate is approximately 2000 mg/kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/m 2basis). The inhalation median lethal dose has not been determined in animals.

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.

Albuterol Sulfate Inhalation Solution, 2.5 mg/0.5 mL (equivalent to 3 mg albuterol sulfate), is a clear, colorless to light yellow solution, and is supplied in plastic sterile unit-dose vials of 0.5 mL each, supplied in individual foil pouches:

NDC 76204-027-01: 30 unit-dose vials, each in an individual pouch.

Albuterol Sulfate Inhalation Solution

2.5 mg/0.5 mL (equivalent to 3 mg albuterol sulfate)

Note: The Albuterol Sulfate Inhalation Solution is concentrated and must be diluted.

Read complete instructions carefully before using.

1. Twist open the top of one Albuterol Sulfate Inhalation Solution unit-of-use container (Figure 1).

                     FIGURE 1

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

                 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).

                 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.

                 FIGURE 4

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.

Mixing Compatibility: The safety and effectiveness of Albuterol sulfate solution for inhalation have not been determined when one or more drugs are mixed with it in a nebulizer.

Store Albuterol Sulfate Inhalation Solution, 0.5%, between 2° and 25° C (36° and 77° F).

ADDITIONAL INSTRUCTIONS________________________________

______________________________________________________

______________________________________________________

______________________________________________________

______________________________________________________

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured for:

Ritedose Pharmaceuticals, LLC

Columbia, SC 29203

Manufactured by:

The Ritedose Corporation

Columbia, SC 29203

March 2024