Label: ALBUTEROL SULFATE solution

Albuterol Sulfate Inhalation Solution 0.083%1

1

(Potency expressed as albuterol, equivalent to 3 mg albuterol sulfate)

PRESCRIBING INFORMATION

FOR INHALATION USE ONLY-NOT FOR INJECTION

Albuterol sulfate inhalation solution is a relatively selective beta 2-adrenergic bronchodilator (see CLINICAL PHARMACOLOGYsection below). Albuterol sulfate, the racemic form of albuterol, has the chemical name α 1-[( 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 576.70 and the molecular formula (C 13H 21NO 3) 2• H 2SO 4. 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 milliliter of albuterol sulfate inhalation solution 0.083% contains 0.83 mg of albuterol (as 1 mg of albuterol sulfate) in an isotonic, sterile, aqueous solution containing sodium chloride; sulfuric acid is used to adjust the pH to between 3 and 5. Albuterol sulfate inhalation solution 0.083% contains no sulfiting agents or preservatives.

Albuterol sulfate inhalation solution is a clear, colorless to light yellow 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 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, 10% to 50% of the beta-receptors in the human heart may be beta 2-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 FEV 1(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 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.

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 FEV 1or PEFR within 2 to 20 minutes following single dose of albuterol inhalation solution. An increase of 15% or more in baseline FEV 1has 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 PEFR 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 beta 2-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.

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 LD 50in rats and mice was greater than 2,000 mg/kg. The inhalational LD 50could not be determined.

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

Unit-dose plastic vial containing Albuterol Sulfate Inhalation Solution 0.083%, 2.5 mg/3 mL 2. 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 68071-3780-2 25 vials per carton / 25 vials per foil pouch

2

(Potency expressed as albuterol, equivalent to 3 mg albuterol sulfate)

Albuterol Sulfate Inhalation Solution 0.083% 3
Note: This is a unit-dose vial. No dilution is required.

Read complete instructions carefully before using.

1. Remove the 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 evenlyas 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% 3between 2° and 25° C (36° and 77° F). Store in pouch until time of use.

ADDITIONAL INSTRUCTIONS:

Manufactured by:
The Ritedose Corporation
Columbia, SC 29203 for
Ritedose Pharmaceuticals, LLC
Columbia, SC 29203

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

RPIN0052
March 2014

3

(Potency expressed as albuterol, equivalent to 3 mg albuterol sulfate).

Manufactured by:
The Ritedose Corporation
Columbia, SC 29203 for
Ritedose Pharmaceuticals, LLC
Columbia, SC 29203

To report SUSPECTED ADVERSEREACTIONS, contact Ritedose

Pharmaceuticals, LLC
at 1-855-806-3300 or FDA
at 1-800-FDA-1088 or www.fda.gov/medwatch

RPIN0052
March 2014