Albuterol Sulfate Inhalation Solution, 0.5%, 2.5mg* / 0.5 mL

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Albuterol Sulfate Inhalation Solution, 0.5% contains albuterol sulfate, USP, the racemic form of albuterol and a relatively selective beta₂-adrenergic bronchodilator (see CLINICAL PHARMACOLOGY section below). Albuterol sulfate has the chemical name α¹-[(tert-Butylamino) methyl]-4-hydroxy-m-xylene-α,α′-diol sulfate (2:1) (salt) and the following chemical structure:
(C₁₃H₂₁NO₃)₂ • H₂SO₄
Mol. Wt. 576.7Albuterol 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 (see DOSAGE AND ADMINISTRATION).Each 0.5 mL Unit-of-Use Vial Contains: ACTIVE: 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-of-Use Vials.Albuterol sulfate inhalation solution is a clear, colorless to light yellow solution.

CLINICAL PHARMACOLOGY

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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

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, data indicate that there is a population of beta₂-receptors in the human heart existing in a concentration between 10% and 50%.  The precise function of these receptors has not been established (see WARNINGS).The pharmacologic effects of beta-adrenergic agonist drugs, including albuterol, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cyclic AMP). 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.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.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY

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displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

Preclinical: Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations that are amounting to approximately 5.0% of the plasma concentrations. In structures outside the brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated 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 is unknown.

CLINICAL STUDIES

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displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

In controlled clinical trials in adults, 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. 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 doses 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 PEFR that was comparable in extent and duration to a 2 mg dose, but doses above 3 mg were associated with heart rate increases of more than 10%.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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.

CONTRAINDICATIONS

id: 4fd55db5-51ab-48ce-b48d-37afd784ca4b
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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 arrythmias (including atrial fibrillation, supraventricular tachycardia, and extrasystoles) have been reported after the use of albuterol sulfate inhalation solution.

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. In isolated cases in children 2 to 12 years of age, tachycardia with rates > 200 beats/min has been observed. As with all sympathomimetic l 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 an mg/m² basis or approximately 300 times the maximum recommended daily inhalation dose for children on a mg/m² basis). In mature rats, the subcutaneous (sc) median lethal dose of albuterol sulfate is approximately 450 mg/kg (approximately  365 times the maximum recommended daily inhalation dose for adults on an mg/m² basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/m² basis). In small young rats, the sc median lethal dose is approximately 2000 mg/kg (approximately 1600 times the maximum recommended daily inhalation dose for adults on a mg/m² basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/m² basis). The inhalational median lethal dose has not been determined in animals.

DOSAGE AND ADMINISTRATION

id: 8a83e24d-4fa7-4937-97f1-8a06f2c43a19
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

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.

HOW SUPPLIED

id: 5e0b4cef-c797-4de8-a19d-b2e908a88365
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Albuterol Sulfate Inhalation Solution, 0.5%, is a clear, colorless to light yellow solution, and is supplied in plastic sterile unit-of-use vials of 0.5 mL each, supplied in individual foil pouches:NDC 0487-9901-30:  30 vials, each in an individual pouchNDC 0487-9901-02:  30 vials, each in an individual foil pouch, robot ready.Rx Only
Manufactured By:
Nephron Pharmaceuticals Corporation
Orlando, FL 32811Distributed By: Cardinal Health Dublin, OH 43017L35881830218

Patient Package Insert

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displayName: SPL PATIENT PACKAGE INSERT SECTION
FDA Article Code: 42230-3

Note: The Albuterol Sulfate Inhalation Solution is concentrated and must be diluted.
Read complete instructions carefully before using.
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).

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Albuterol Sulfate Inhalation Solution, 0.5%*2.5 mg* / 0.5ML5 x 0.5 ML Sterile Unit-of-use vials