Albuterol 1 MG/ML Inhalant Solution
WARNINGS
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.
Albuterol sulfate inhalation solution contains the preservative benzalkonium chloride.
Benzalkonium chloride has been associated with bronchospasm in a dose-dependent manner.
In patients who receive high doses (e.g., continuous nebulization) of albuterol sulfate inhalation solution and bronchospasm does not resolve, consider a trial of short-acting bronchodilator that does not contain the preservative benzalkonium chloride [see Dosage and Administration ].
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 betaadrenergic 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, e.g., corticosteroids.
Microbial Contamination: It is recommended that each multi-dose bottle of albuterol be used for only one patient.
Nosocomial outbreaks of pneumonia have occurred in hospitals when one multi-dose bottle of albuterol was used to treat more than one patient.
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.
DRUG INTERACTIONS
Drug Interactions Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with albuterol.
If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.
Monoamine Oxidase Inhibitors or Tricyclic Antidepressants: Albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of albuterol on the vascular system may be potentiated.
Beta-Blockers: Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as albuterol sulfate inhalation solution, but may produce severe bronchospasm in asthmatic patients.
Therefore, patients with asthma should not normally be treated with beta-blockers.
However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma.
In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
Diuretics: The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics.
Digoxin: Mean decreases of 16% to 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days.
The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear.
Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and albuterol.
OVERDOSAGE
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/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/m 2 basis or approximately 300 times the maximum recommended daily dose for children on a mg/m 2 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/m 2 basis or approximately 135 times the maximum recommended daily inhalation dose for children on a mg/m 2 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/m 2 basis or approximately 600 times the maximum recommended daily inhalation dose for children on a mg/m 2 basis).
The inhalational median lethal dose has not been determined in animals.
DESCRIPTION
Albuterol Sulfate Inhalation Solution, 0.5% is a sterile solution that contains albuterol sulfate, USP, the racemic form of albuterol and a relatively selective beta 2 -adrenergic bronchodilator (see CLINICAL PHARMACOLOGY section below).
Albuterol sulfate 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 576.71 and the molecular formula (C 13 H 21 NO 3 ) 2 •H 2 SO 4 .
Albuterol 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 (3.5-4.2).
PRESERVATIVE ADDED: Benzalkonium Chloride 0.01%.
Albuterol sulfate inhalation solution contains no sulfiting agents.
It is supplied in 20 mL bottles.
Albuterol Sulfate Inhalation Solution is a clear, colorless sterile solution.
Chemical Structure
HOW SUPPLIED
Product: 50090-0517
INDICATIONS AND USAGE
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.
PEDIATRIC USE
Pediatric Use The safety and effectiveness of albuterol sulfate inhalation solution have been established in children 2 years of age and older.
Use of albuterol sulfate inhalation solution in these age-groups is supported by evidence from adequate and well-controlled studies of albuterol sulfate inhalation solution in adults; the likelihood that the disease course, pathophysiology, and the drug’s effect in pediatric and adult patients are substantially similar; and published reports of trials in pediatric patients 3 years of age or older.
The recommended dose for the pediatric population is based upon three published dose comparison studies of efficacy and safety in children 5 to17 years, and on the safety profile in both adults and pediatric patients at doses equal to or higher than the recommended doses.
The safety and effectiveness of albuterol sulfate inhalation solution in children below 2 years of age have not been established.
PREGNANCY
Pregnancy Pregnancy Category C: Albuterol has been shown to be teratogenic in mice.
A study in CD-1 mice at subcutaneous (sc) doses of 0.025, 0.25, and 2.5 mg/kg (approximately 1/100, 1/10, and 1.0 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m 2 basis) showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg.
The drug did not induce cleft palate formation at the lowest dose, 0.025 mg/kg.
Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated with 2.5 mg/kg of isoproterenol (positive control) subcutaneously (approximately 1.0 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis).
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol was administered orally at a 50-mg/kg dose (approximately 80 times the maximum recommended daily inhalation dose for adults on a mg/m 2 basis).
There are no adequate and well-controlled studies in pregnant women.
Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with albuterol.
Some of the mothers were taking multiple medications during their pregnancies.
No consistent pattern of defects can be discerned, and a relationship between albuterol use and congenital anomalies has not been established.
NUSRING MOTHERS
Nursing Mothers It is not known whether this drug is excreted in human milk.
Because of the potential for tumorigenicity shown for albuterol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
INFORMATION FOR PATIENTS
Information for Patients The action of albuterol sulfate inhalation solution may last up to 6 hours or longer.
Albuterol sulfate inhalation solution should not be used more frequently than recommended.
Do not increase the dose or frequency of albuterol sulfate inhalation solution without consulting your physician.
If you find that treatment with albuterol sulfate inhalation solution becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately.
While you are using albuterol sulfate inhalation solution, other inhaled drugs and asthma medications should be taken only as directed by your physician.
Common adverse effects include palpitations, chest pain, rapid heart rate, and tremor or nervousness.
If you are pregnant or nursing, contact your physician about use of albuterol sulfate inhalation solution.
Effective and safe use of albuterol sulfate inhalation solution includes an understanding of the way that it should be administered.
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.
See illustrated “ Patient’s Instructions for Use .”
DOSAGE AND ADMINISTRATION
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.
In patients who receive high doses (e.g., continuous nebulization) of Albuterol Sulfate Inhalation Solution and bronchospasm does not resolve, consider a trial of short acting bronchodilator that does not contain the preservative benzalkonium chloride [see WARNINGS – Paradoxical Bronchospasm ].