Albuterol sulfate inhalation solution is a relatively selective beta2-adrenergic bronchodilator (see CLINICAL PHARMACOLOGY section below). Albuterol sulfate, the racemic form of albuterol, has the chemical name α1[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-α,α´diol sulfate (2:1) (salt), and the following structural formula:

Albuterol sulfate has a molecular weight of 576.71 and the molecular formula (C13H21 NO3)2 •H2SO4. Albuterol sulfate is a white or practically white powder, freely soluble in water and slightly soluble in alcohol.

The World Health Organization recommended name for albuterol base is salbutamol.

Albuterol sulfate inhalation solution 0.083% requires no dilution before administration.

Each mL of albuterol sulfate inhalation solution (0.083%) contains 0.83 mg of albuterol (as 1 mg of albuterol sulfate USP) in an isotonic, sterile, aqueous solution containing sodium chloride, edetate disodium and sodium citrate; hydrochloric acid is used to adjust the pH between 3 and 5. Albuterol sulfate inhalation solution (0.083%) contains no sulfiting agents.

Albuterol sulfate inhalation solution is a clear, colorless solution.

The prime action of beta-adrenergic drugs is to stimulate adenyl cyclase, the enzyme which catalyzes the formation of cyclic-3’,5’-adenosine monophosphate (cyclic AMP) from adenosine triphosphate (ATP). The cyclic AMP thus formed mediates the cellular responses. In vitro studies and in vivo pharmacologic studies have demonstrated that albuterol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. While it is recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, 10% to 50% of the beta-receptors in the human heart may be beta2-receptors. The precise function of these receptors, however, is not yet established. 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 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.

Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following IPPB (intermittent positive-pressure breathing) 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 FEV1 (forced expiratory volume in one second) and peak flow rate. It has been demonstrated that following oral administration of 4 mg albuterol, the elimination half-life was five to six hours.

Animal studies show that albuterol does not pass the blood-brain barrier. Recent studies in laboratory animals (minipigs, rodents, and dogs) recorded the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines were administered concurrently. The significance of these findings when applied to humans is currently unknown.

In controlled clinical trials, most patients exhibited an onset of improvement in pulmonary function within 5 minutes as determined by FEV1. FEV1 measurements 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 FEV1 over baseline values) continued for 3 to 4 hours in most patients and in some patients continued up to 6 hours.

In repetitive dose studies, continued effectiveness was demonstrated throughout the three-month period of treatment in some patients.

Published reports of trials in asthmatic children aged 3 years or older have demonstrated significant improvement in either FEV1 or PEFR within 2 to 20 minutes following single dose of albuterol inhalation solution. An increase of 15% or more in baseline FEV1 has been 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. Single doses of 3, 4 or 10 mg resulted in improvement in baseline PER that was comparable to extent and duration to a 2 mg dose, but doses above 3 mg were associated with heart rate increases of more than 10%.

Albuterol sulfate inhalation solution is indicated for the relief of bronchospasm in patients 2 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 any of its components.

As with other inhaled beta-adrenergic agonists, albuterol sulfate inhalation solution can produce paradoxical bronchospasm, which can be life threatening. If it occurs, the preparation should be discontinued immediately and alternative therapy instituted.

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. In individual patients, any beta2-adrenergic agonist, including albuterol solution for inhalation, may have a clinically significant cardiac effect.

Immediate hypersensitivity reactions may occur after administration of albuterol as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.

Clinical Trial Experience

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:

Central Nervous System: tremors (20%), dizziness (7%), nervousness (4%), headache (3%), insomnia (1%).

Gastrointestinal: nausea (4%), dyspepsia (1%).

Ear, Nose and Throat: pharyngitis (<1%), nasal congestion (1%).

Cardiovascular: tachycardia (1%), hypertension (1%).

Respiratory: bronchospasm (8%), cough (4%), bronchitis (4%), wheezing (1%).

No clinically relevant laboratory abnormalities related to albuterol sulfate inhalation solution administration were determined in these studies.

In comparing the adverse reactions reported for patients treated with albuterol sulfate inhalation solution with those of patients treated with isoproterenol during clinical trials of three months, the following moderate to severe reactions, as judged by the investigators, were reported. This table does not include mild reactions.

Postmarketing Experience

Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, arrhythmias (including atrial fibrillations, supraventricular tachycardia, extrasystoles) and metabolic acidosis have been reported after the use of albuterol sulfate inhalation solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Manifestations of overdosage may include seizures, anginal pain, hypertension, hypokalemia, tachycardia with rates up to 200 beats/min, and exaggeration of the pharmacological effects listed in ADVERSE REACTIONS. In isolated cases in children 2 to 12 years of age, tachycardia with rates >200 beats/min has been observed.

The oral LD50 in rats and mice was greater than 2,000 mg/kg. The inhalational LD50 could not be determined.

There is insufficient evidence to determine if dialysis is beneficial for overdosage of albuterol inhalation solution.

Adults and Children 2 to 12 Years of Age

The usual dosage for adults and for children weighing at least 15 kg is 2.5 mg of albuterol (one vial) administered three to four times daily by nebulization. Children weighing <15 kg who require <2.5 mg/dose (i.e., less than a full vial) should use albuterol inhalation solution, 0.5% instead of albuterol inhalation solution, 0.083%. More frequent administration or higher doses are not recommended. To administer 2.5 mg of albuterol, administer the entire contents of one sterile unit dose vial (3 mL of 0.083% inhalation solution) by nebulization. The flow rate is regulated to suit the particular nebulizer so that albuterol inhalation solution will be delivered over approximately 5 to 15 minutes.

The use of albuterol sulfate inhalation solution can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimum benefit from regular use of the inhalation 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.

Unit-dose plastic vial containing Albuterol Sulfate Inhalation Solution 0.083%, 2.5 mg/3 mL* (*potency expressed as albuterol). Equivalent to 0.5 mL albuterol (as the sulfate) 0.5% (2.5 mg albuterol) diluted to 3 mL. Supplied in cartons as listed below.

NDC 71205-641-25    carton of 25 vials (5 vials per foil pouch)

Storage

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

Dispense with Patient's Instructions For Use available at: https://www.sunpharma.com/usa/products



Albuterol (al-BUE-ter-ol) Sulfate Inhalation Solution 0.083%*

(*Potency expressed as albuterol)

Note: This is a unit-dose vial. No dilution is required.

Read complete instructions carefully before using.

1. Remove vial from the foil pouch.

2. Twist the cap completely off the vial and squeeze the contents into the nebulizer reservoir (Figure 1).

3. Connect the nebulizer reservoir to the mouthpiece or face mask (Figure 2).

4. Connect the nebulizer to the compressor.

5. Sit in a comfortable, upright position; place the mouthpiece in your mouth (Figure 3) (or put on the face mask); and turn on the compressor.

6. 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.

7. Clean the nebulizer (see manufacturer's instructions).

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



Store Albuterol Sulfate Inhalation Solution 0.083% at 20° to 25° C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F). Store in pouch until time of use.



ADDITIONAL INSTRUCTIONS:______________________



Dispense with Patient's Instructions For Use available at: https://www.sunpharma.com/usa/products



 Distributed by:

Sun Pharmaceutical Industries, Inc.

Cranbury, NJ 08512



Manufactured by:

Sun Pharmaceutical Medicare Limited

Baska Ujeti Road, Ujeti

Halol-389350, Gujarat, India

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

ISS. 12/2021

NDC 71205-641-25

Albuterol Sulfate Inhalation Solution, 0.083%*

2.5 mg*/3 mL

*Potency expressed as albuterol

For Inhalation Only

Not for Injection

Equivalent to 0.5 mL Albuterol Sulfate 0.5%* diluted to 3 mL normal saline

Rx only

25 X 3 mL Sterile Unit-Dose Vials

(5 Unit-Dose Vials per pouch, 5 pouches per carton)

PHARMACIST:  Dispense with “Patient's Instructions For Use” to each patient.