Description
id: 4E2151B0-AEB8-024A-101A-1C6192305F93
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 structural formula:(C13H21NO3)2•H2SO4
Mol. Wt. 576.71Albuterol 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 the appropriate volume of the solution (see DOSAGE AND ADMINISTRATION) with sterile normal saline solution to a total volume of 3 mL and administer by nebulization.Each mL Contains: ACTIVE: Albuterol sulfate equivalent to 5 mg of albuterol in an aqueous solution. Sulfuric Acid may be added to adjust pH (3.0-5.0).PRESERVATIVE ADDED: Benzalkonium Chloride 0.01%. Albuterol sulfate inhalation solution contains no sulfiting agents.Albuterol sulfate inhalation solution is a clear, colorless to light yellow solution.
Clinical Pharmacology
id: DE9ABEBE-1E8A-9CE5-D247-22438D6EF816
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.Pharmacokinetics: Studies in asthmatic patients have shown that less than 20% of a single albuterol dose was absorbed following either intermittent positive-pressure breathing (IPPB) 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 within 24 hours after drug administration. Following a 3-mg dose of nebulized albuterol in adults, the maximum albuterol plasma levels at 0.5 hours were 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 1 second) and peak flow rate. It has been demonstrated that following oral administration of 4 mg of albuterol, the elimination half-life was 5 to 6 hours.Preclinical: Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations 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 are administered concurrently. The clinical significance of these findings is unknown.Clinical Trials: 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, with some patients continuing 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
id: D31A9F84-8125-4F93-7C94-CE9A0E5060E8
displayName: Indications and Usage section
FDA Article Code: 34067-9
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.
Contraindications
id: D42E2847-C5CF-6D66-2C56-46AE801CB3C2
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.
Warnings
id: E9266448-8D4F-DE06-BBF4-05B276FE2E4C
displayName: Warnings section
FDA Article Code: 34071-1
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 canister or vial.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.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.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 reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema.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, eg, corticosteroids.Microbial Contamination: To avoid microbial contamination, proper aseptic technique should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.
Adverse Reactions
id: AEB25311-E584-1227-7FFD-1ED8A2B8B68B
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 that were considered probably or possibly drug related:
Percent Incidence of Adverse Reactions
| Reaction |
Percent Incidence
Reaction n=135 |
| Central Nervous System |
|
| Tremors |
20% |
| Dizziness |
7% |
| Nervousness |
4% |
| Headache |
3% |
| Sleeplessness |
1% |
| Gastrointestinal |
|
| Nausea |
4% |
| Dyspepsia |
1% |
| Ear, nose and throat |
|
| Nasal congestion |
1% |
| Pharyngitis |
<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.Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventicular tachycardia, extrasystoles) have been reported after the use of albuterol sulfate inhalation solution.
Overdosage
id: F58EBDF0-65BD-24AB-DDE5-667B2DDB2834
displayName: Overdosage section
FDA Article Code: 34088-5
The expected symptoms with overdosage are those of excessive betaadrenergic 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/min, 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 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/m2 basis or approximately 300 times the maximum recommended daily 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 a 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: B27B20BA-3034-D85C-4459-3EBB23C68436
displayName: Dosage and Administration section
FDA Article Code: 34068-7
To avoid microbial contamination, proper aseptic techniques should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used.Children 2 to 12 Years of Age: For children 2 to 12 years of age, initial dosing should be based upon body weight (0.1 to 0.15 mg/kg per dose), with subsequent dosing titrated to achieve the desired clinical response. Dosing should not exceed 2.5 mg three to four times daily by nebulization. The following table outlines approximate dosing according to body weight.
| Approximate Weight (kg) |
Approximate Weight (lb) |
Dose (mg) |
Volume of Inhalation Solution |
| 10-15 |
22-33 |
1.25 |
0.25 mL |
| >15 |
>33 |
2.5 |
0.5 mL |
The appropriate volume of the 0.5% inhalation solution should be diluted in sterile normal saline solution to a total volume of 3 mL prior to administration via nebulization.Adults and Children Over 12 Years of Age: The usual dosage for adults and children 12 years of age and older is 2.5 mg of albuterol administered three to four 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% inhalation solution with 2.5 mL of sterile normal saline solution. 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.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 optimal 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 that would require reassessment of therapy.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.
How Supplied
id: C75E6F44-6A56-23D4-0144-A3676034D435
displayName: How Supplied section
FDA Article Code: 34069-5
Albuterol sulfate inhalation solution, 0.5% is supplied in amber glass bottles, with a calibrated dropper and with patient instructions in the following size:20 mL bottles (NDC 59930-1647-2).
Storage
id: 336283C3-319B-ADB8-7D17-1914BA8C618D
displayName: STORAGE AND HANDLING SECTION
FDA Article Code: 44425-7
Store between 2°-25°C (36°-77°F).KEEP OUT OF REACH OF CHILDREN.*Potency expressed as albuterolRx onlyFOR ORAL INHALATION ONLY
Manufacturer Information
id: 34ABCED1-6EA9-CD5E-3FD6-81A0BED1002C
displayName: SPL Unclassified section
FDA Article Code: 42229-5
Bausch & Lomb Incorporated
Tampa, FL 33637©Bausch & Lomb IncorporatedRevised May 20089116500 (Folded)
9116600 (Flat)PHARMACIST — DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT
Patient Instructions For Use
id: 15F9B4E0-AAC8-1A8A-39A2-6EB9EAF40906
displayName: SUPPLEMENTAL PATIENT MATERIAL
FDA Article Code: 38056-8
Albuterol Sulfate Inhalation Solution, 0.5%**Potency expressed as albuterolRead complete instructions carefully beforeusing.1. Draw the appropriate volume of albuterol sulfate inhalation solution, 0.5% into the specially marked dropper that comes with each multidose bottle. For children 12 years of age and under, the volume is based upon body weight. Use the dropper volume prescribed by your doctor.2. Squeeze the solution into the nebulizer reservoir through the appropriate opening, taking care not to touch the tip of the dropper.3. Add sterile normal saline solution, as your doctor has directed. A general guideline for the amount of saline to add is: For children using 0.25 mL or 1.25 mg of albuterol sulfate inhalation solution, add 2.75 mL of sterile normal saline. For children or adults using 0.5mL or 2.5mg of albuterol sulfate inhalation solution, add 2.5 mL of sterile normal saline.4. Gently swirl the nebulizer to mix the contents and connect it with the mouthpiece or face mask.5. Connect the nebulizer to the compressor.6. Sit in a comfortable, upright position; place the mouthpiece in your mouth (or put on the face mask); and turn on the compressor.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).Note: Use only as directed by your physician.More frequent administration or higherdoses are not recommended.To avoid microbial contamination, proper aseptic techniques should be used each time the bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the bottle with any surface, including the nebulizer reservoir and associated ventilatory equipment. In addition, if the solution changes color or becomes cloudy, it should not be used. The safety and effectiveness of albuterol sulfate inhalation solution have not been determined when one or more drugs are mixed with it in a nebulizer. Check with your doctor beforemixing anymedications in your nebulizer.Storage: Store between 2°-25°C (36°- 77° F).ADDITIONAL INSTRUCTIONS:______________________________________________________________________Bausch & Lomb Incorporated
Tampa, FL 33637©Bausch & Lomb IncorporatedRevised May 20089116500 (Folded)
9116600 (Flat)
