Albuterol Sulfate Inhalation Solution, 0.63 mg* / 3 mL and 1.25 mg* / 3 mL

/Albuterol Sulfate Inhalation Solution, 0.63 mg* / 3 mL and 1.25 mg* / 3 mL
Albuterol Sulfate Inhalation Solution, 0.63 mg* / 3 mL and 1.25 mg* / 3 mL2018-09-06T09:12:40+00:00

Prescription Drug Name:

Albuterol Sulfate Inhalation Solution, 0.63 mg* / 3 mL and 1.25 mg* / 3 mL

ID:

1b4f9d70-940c-4e94-acc9-7871532ec575

Code:

34391-3

DESCRIPTION


id: a5b4bc21-628c-44a2-8fc5-34d9cae2d00e
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Albuterol sulfate inhalation solution is a sterile, clear, colorless solution of the sulfate salt of racemic albuterol, albuterol sulfate. Albuterol sulfate is a relatively selective beta2-adrenergic bronchodilator (see CLINICAL PHARMACOLOGY). The chemical name for albuterol sulfate is α1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-α,α’-diol sulfate (2:1) (salt), and its established chemical structure is as follows: The molecular weight of albuterol sulfate is 576.7 and the empirical formula is (C13H21NO3)2 • H2SO4. Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization’s recommended name for albuterol is salbutamol. Albuterol sulfate inhalation solution is supplied in two strengths in unit-dose vials. Each unit-dose vial contains either 0.75 mg of albuterol sulfate (equivalent to 0.021% or 0.63 mg of albuterol) or 1.5 mg of albuterol sulfate (equivalent to 0.042% or 1.25 mg of albuterol) with sodium chloride and sulfuric acid in a 3 mL isotonic, sterile, aqueous solution. Sodium chloride is added to adjust isotonicity of the solution and sulfuric acid is added to adjust pH of the solution to between 3 and 5 (see HOW SUPPLIED). Albuterol sulfate inhalation solution does not require dilution prior to administration by nebulization. For albuterol sulfate inhalation solution, like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari LC Plus™ nebulizer (with face mask or mouthpiece) connected to a Pari PRONEB™ compressor, under in vitro conditions, the mean delivered dose from the mouth piece (% nominal dose) was approximately 43% of albuterol (0.042% or 1.25 mg strength) and 39% of albuterol (0.021% or 0.63 mg strength) at a mean flow rate of 3.6 L/min. The mean nebulization time was 15 minutes or less. Albuterol sulfate inhalation solution should be administered from a jet nebulizer at an adequate flow rate, via a mouthpiece or face mask (see DOSAGE AND ADMINISTRATION).

CLINICAL PHARMACOLOGY


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

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, recent data indicate that 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. 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


id: a3fa48cc-7de7-4de8-a2cf-9c4c403d9ff8
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9

Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those found in 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 are administered concurrently. The clinical significance of these findings is unknown.

CLINICAL STUDIES


id: a4d1fb94-e0e5-44ea-af37-059eb94fc8d0
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

The safety and efficacy of albuterol sulfate inhalation solution was evaluated in a 4-week, multi-center, randomized, double-blind, placebo-controlled, parallel group study in 349 children 6 to 12 years of age with mild-to-moderate asthma (mean baseline FEV1 60% to 70% of predicted). Approximately half of the patients were also receiving inhaled corticosteroids. Patients were randomized to receive albuterol sulfate inhalation solution 0.63 mg (0.021%), albuterol sulfate inhalation solution 1.25 mg (0.042%), or placebo three times a day administered via a Pari LC Plus™ nebulizer and a Pari PRONEB™ compressor. Racemic albuterol, delivered by a chlorofluorocarbon (CFC) metered dose inhaler (MDI) or nebulized, was used on an as-needed basis as the rescue medication. Efficacy, as measured by the mean percent change from baseline in the area under the 6-hour curve for FEV1, was demonstrated for both active treatment regimens (n=112 [1.25 mg or 0.042% group] and n=110 [0.63 mg or 0.021% group]) compared with placebo (n=110) on day 1 and day 28. Figures 1 and 2 illustrate the mean percentage change from pre-dose FEV1 on day 1 and day 28, respectively. The mean baseline FEV1 for all patients was 1.49 L.
The onset of a 15% increase in FEV1 over baseline for both doses of albuterol sulfate inhalation solution was seen at 30 minutes (the first post-dose assessment). The mean time to peak effect was approximately 30 to 60 minutes for both doses on day 1 and after 4 weeks of treatment. The mean duration of effect, as measured by a >15% increase from baseline in FEV1, was approximately 2.5 hours for both doses on day 1 and approximately 2 hours for both doses after 4 weeks of treatment. In some patients, the duration of effect was as long as 6 hours.

INDICATIONS AND USAGE


id: ab7cebc5-dfb9-47cc-a675-d76d24c4ef17
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Albuterol sulfate inhalation solution is indicated for the relief of bronchospasm in patients 2 to 12 years of age with asthma (reversible obstructive airway disease).

CONTRAINDICATIONS


id: a5ea4aac-7d18-4bf5-b088-87294fcf4760
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

ADVERSE REACTIONS


id: aea36ff0-ad55-488b-81ac-d0193749470a
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Adverse events reported in >1% of patients receiving albuterol sulfate inhalation solution and more frequently than in patients receiving placebo in a four-week double-blind study are listed in the following table.

Table 1: Adverse Events with an Incidence of >1% of Patients Receiving Albuterol Sulfate and Greater than Placebo (expressed as % of treatment group)
1.25 mg
(0.042%)
Albuterol Sulfate
(n = 115)
0.63 mg
(0.021%)
Albuterol Sulfate
(n = 117)
Placebo
(n = 117)
Asthma Exacerbation 13 11.1 8.5
Otitis Media 4.3 0.9 0
Allergic Reaction 0.9 3.4 1.7
Gastroenteritis 0.9 3.4 0.9
Cold Symptoms 0 3.4 1.7
Flu Syndrome 2.6 2.6 1.7
Lymphadenopathy 2.6 0.9 1.7
Skin/Appendage Infection 1.7 0 0
Urticaria 1.7 0.9 0
Migraine 0.9 1.7 0
Chest Pain 0.9 1.7 0
Bronchitis 0.9 1.7 0.9
Nausea 1.7 0.9 0.9
There was one case of ST segment depression in the 1.25 mg (0.042%) albuterol sulfate inhalation solution treatment group. No clinically relevant laboratory abnormalities related to albuterol sulfate inhalation solution administration were seen in this study.

OVERDOSAGE


id: af9b9ef5-f7c3-49da-9651-45a5b2ec65d4
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 symptoms such as 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, insomnia, and exaggeration of the pharmacological effects listed in ADVERSE REACTIONS. 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 580 times the maximum recommended daily inhalation dose of albuterol sulfate on a mg/m2 basis). The subcutaneous median lethal dose of albuterol sulfate in mature rats and small young rats is approximately 450 mg/kg and 2000 mg/kg, respectively (approximately 260 and 1200 times the maximum recommended daily inhalation dose of albuterol sulfate on a mg/m2 basis). The inhalation median lethal dose has not been determined in animals.

DOSAGE AND ADMINISTRATION


id: af922da4-f10b-43dd-9b2e-b20c57a147cf
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The usual starting dosage for patients 2 to 12 years of age is 1.25 mg (0.042%) or 0.63 mg (0.021%) of albuterol sulfate inhalation solution administered 3 or 4 times daily, as needed, by nebulization. More frequent administration is not recommended. To administer 1.25 mg or 0.63 mg of albuterol, use the entire contents of one unit-dose vial (3 mL of 0.042% [1.25 mg] or 3 mL of 0.021% [0.63 mg] inhalation solution) by nebulization. Adjust nebulizer flow rate to deliver albuterol sulfate inhalation solution over 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. Patients 6 to 12 years of age with more severe asthma (baseline FEV1 less than 60% predicted), weight > 40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose. Albuterol sulfate inhalation solution has not been studied in the setting of acute attacks of bronchospasm. A 2.5 mg dose of albuterol provided by a higher concentration product (2.5 mg albuterol per 3 mL) may be more appropriate for treating acute exacerbations, particularly in children 6 years old and above. 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 drug compatibility (physical and chemical), clinical efficacy and safety of albuterol sulfate inhalation solution, when mixed with other drugs in a nebulizer have not been established. The safety and efficacy of albuterol sulfate inhalation solution have been established in clinical trials when administered using the Pari LC Plus™ nebulizer and Pari PRONEB™ compressor. The safety and efficacy of albuterol sulfate inhalation solution when administered with other nebulizer systems have not been established. Albuterol sulfate inhalation solution should be administered via jet nebulizer connected to an air compressor with adequate air flow, equipped with a mouthpiece or suitable face mask.

HOW SUPPLIED


id: 46bdab88-1065-4765-8766-f4df52904ae7
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Albuterol sulfate inhalation solution is supplied as a prediluted 3 mL, clear, colorless, sterile, preservative-free, aqueous solution in 1.25 mg (0.042%) of albuterol (equivalent to 1.5 mg of albuterol sulfate in 3 mL) in unit-dose low-density polyethylene (LDPE) vials. Each unit-dose LDPE vial is protected in a foil-pouch, and each foil pouch contains 1 unit-dose LDPE vial. Each strength of albuterol sulfate inhalation solution is available in a shelf carton containing multiple foil pouches.  Albuterol Sulfate Inhalation Solution, 0.042% (1.25 mg / 3 mL) (potency expressed as albuterol equivalent to 1.5 mg albuterol sulfate per 3 mL) in unit-dose vials and is available in the following packaging configurations: NDC 54868-5709-0                 30 foil pouches, each containing 1 vial, total 30 vials per carton

Patient Package Insert


id: a0f4f085-f8b5-4ab0-b876-1f295fd9c59c
displayName: Spl Patient Package Insert Section
FDA Article Code: 42230-3

Read this patient information completely every time your prescription is filled as information may have changed. Keep these instructions with your medication, as you may want to read them again. Albuterol sulfate inhalation solution should only be used under the direction of a physician. Your physician and pharmacist have more information about albuterol sulfate inhalation solution and the condition for which it has been prescribed. Contact them if you have additional questions.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL


id: 8a295d0a-b191-45cb-9fbc-91341fba5190
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Principal Display – Carton (1.25* mg)