Albuterol Information
Albuterol (Salbutamol) Description
The active component of Albuterol (Salbutamol) Inhalation Aerosol is Albuterol (Salbutamol) , USP, racemic α-[(-butylamino)methyl]-4-hydroxy--xylene-α,α'-diol) and a relatively selective beta-adrenergic bronchodilator having the following structural formula:
Albuterol (Salbutamol) is the official generic name in the United States. The World Health Organization recommended name for the drug is salbutamol. The molecular weight of Albuterol (Salbutamol) is 239.32, and the molecular formula is CHNO. Albuterol (Salbutamol) is a white to off-white crystalline solid. It is soluble in ethanol, sparingly soluble in water, and very soluble in chloroform.
Albuterol (Salbutamol) Inhalation Aerosol is a pressurized metered-dose aerosol unit for oral inhalation. It contains a microcrystalline (95%≤10µm) suspension of Albuterol (Salbutamol) in propellants (trichloromonofluoromethane and dichlorodifluoromethane) with oleic acid. Each actuation delivers 100 mcg of Albuterol (Salbutamol) from the valve and 90 mcg of Albuterol (Salbutamol) from the mouthpiece. Each 17 g canister provides 200 inhalations.
Albuterol (Salbutamol) Clinical Pharmacology
The pharmacologic effects of beta-adrenergic agonist drugs, including Albuterol (Salbutamol) , 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 (Salbutamol) 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 (Salbutamol) , 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 (Salbutamol) 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--methyl transferase.
The effects of rising doses of Albuterol (Salbutamol) and isoproterenol aerosols were studied in volunteers and asthmatic patients. Results in normal volunteers indicated that Albuterol (Salbutamol) is one half to one quarter as active as isoproterenol in producing increases in heart rate. In asthmatic patients similar cardiovascular differentiation between the two drugs was also seen.
Albuterol (Salbutamol) Indications And Usage
Albuterol (Salbutamol) Inhalation Aerosol is indicated for the prevention and relief of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease and for the prevention of exercise-induced bronchospasm in patients 4 years of age and older.
Albuterol (Salbutamol) Inhalation Aerosol can be used with or without concomitant steroid therapy.
Albuterol (Salbutamol) Contraindications
Albuterol (Salbutamol) Inhalation Aerosol is contraindicated in patients with a history of hypersensitivity to Albuterol (Salbutamol) or any of its components.
Albuterol (Salbutamol) Warnings
Immediate hypersensitivity reactions may occur after administration of Albuterol (Salbutamol) Inhalation Aerosol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
The contents of Albuterol (Salbutamol) Inhalation Aerosol are under pressure. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw container into fire or incinerator. Keep out of reach of children.
Albuterol (Salbutamol) Precautions
Albuterol (Salbutamol) , as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after use of any beta-adrenergic bronchodilator.
Large doses of intravenous Albuterol (Salbutamol) have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, Albuterol (Salbutamol) may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.
Although there have been no reports concerning the use of Albuterol (Salbutamol) Inhalation Aerosol during labor and delivery, it has been reported that high doses of Albuterol (Salbutamol) administered intravenously inhibit uterine contractions. Although this effect is extremely unlikely as a consequence of aerosol use, it should be kept in mind.
The action of Albuterol (Salbutamol) Inhalation Aerosol may last up to 6 hours or longer. Albuterol (Salbutamol) Inhalation Aerosol should not be used more frequently than recommended. Do not increase the dose or frequency of Albuterol (Salbutamol) Inhalation Aerosol without consulting your physician. If you find that treatment with Albuterol (Salbutamol) Inhalation Aerosol 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 (Salbutamol) Inhalation Aerosol, other inhaled drugs and asthma medications should be taken only 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 (Salbutamol) Inhalation Aerosol. Effective and safe use of Albuterol (Salbutamol) Inhalation Aerosol includes an understanding of the way that should be administered.
In general, the technique for administering Albuterol (Salbutamol) Inhalation Aerosol to children is similar to that for adults, since children’s smaller ventilatory exchange capacity automatically provides proportionally smaller aerosol intake. Children should use Albuterol (Salbutamol) Inhalation Aerosol under adult supervision, as instructed by the patient’s physician.
See illustrated Patient’s Instructions for Use accompanying the product package insert.
In a 2-year study in Sprague-Dawley rats, Albuterol (Salbutamol) sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 2.0, 10, and 50 mg/kg (approximately 15, 70, and 340 times, respectively, the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 6, 30, and 160 times, respectively, the maximum recommended daily inhalation dose for children on a mg/m basis). In another study this effect was blocked by the coadministration of propranolol, a non-selective beta-adrenergic antagonist. In an 18-month study in CD-1 mice Albuterol (Salbutamol) sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg (approximately 1700 times the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 800 times the maximum recommended daily inhalation dose for children on a mg/m basis). In a 22-month study in the Golden hamster Albuterol (Salbutamol) sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg (approximately 225 times the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 110 times the maximum recommended daily inhalation dose for children on a mg/m basis).
Albuterol (Salbutamol) sulfate was not mutagenic in the Ames test with or without metabolicactivation using tester strains TA1537, TA1538, and TA98 or WP2, WP2uvrA, and WP67. No forward mutation was seen in yeast strain S9 nor any mitotic gene conversion in yeast strain JD1 with or without metabolic activation. Fluctuation assays in TA98 and WP2, both with metabolic activation, were negative. Albuterol (Salbutamol) sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at intraperitoneal doses of up to 200 mg/kg.
Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg (approximately 340 times the maximum recommended daily inhalation dose for adults on a mg/m basis).
Albuterol (Salbutamol) Adverse Reactions
The adverse reactions to Albuterol (Salbutamol) are similar in nature to reactions to other sympathomimetic agents, although the incidence of certain cardiovascular effects is lower with Albuterol (Salbutamol) .
Cases of urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles) have been reported after the use of Albuterol (Salbutamol) Inhalation Aerosol. In addition, Albuterol (Salbutamol) , like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, sleeplessness, and unusual taste.
Albuterol (Salbutamol) 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 , 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.
As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of Albuterol (Salbutamol) Inhalation Aerosol. Treatment consists of discontinuation of Albuterol (Salbutamol) Inhalation Aerosol 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 (Salbutamol) Inhalation Aerosol.
The oral median lethal dose of Albuterol (Salbutamol) sulfate in mice is greater than 2000 mg/kg (approximately 6800 times the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 3200 times the maximum recommended daily inhalation dose for children on a mg/m basis). In mature rats, the subcutaneous median lethal dose of Albuterol (Salbutamol) sulfate is approximately 450 mg/kg (approximately 3000 times the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 1400 times the maximum recommended daily inhalation dose for children on a mg/m basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/kg (approximately 14,000 times the maximum recommended daily inhalation dose for adults on a mg/m basis or approximately 6400 times the maximum recommended daily inhalation dose for children on a mg/m basis). The inhalation median lethal dose has not been determined in animals.
Albuterol (Salbutamol) Dosage And Administration
For treatment of acute episodes of bronchospasm or prevention of asthmatic symptoms, the usual dosage for adults and children 4 years of age and older is 2 inhalations repeated every 4 to 6 hours; in some patients, 1 inhalation every 4 hours maybe sufficient. More frequent administration or a larger number of inhalations are not recommended. It is recommended to “test spray” Albuterol (Salbutamol) Inhalation Aerosol. Do this by spraying 4 times into the air before using for the first time and when the inhaler has not been used for a prolonged period of time. (i.e., more than 4 weeks). The use of Albuterol (Salbutamol) Inhalation Aerosol 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 inhaler. Safe usage for periods extending over several years has been documented.
If a previously effective dosage regimen fails to provide the usual response, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
Albuterol (Salbutamol) How Supplied
Albuterol (Salbutamol) Inhalation Aerosol is supplied in 17 g canisters containing 200 metered inhalations, in boxes of one. Each actuation delivers 100 mcg of Albuterol (Salbutamol) from the valve and 90 mcg of Albuterol (Salbutamol) from the mouthpiece. Each canister is supplied with an oral adapter with the hourglass logo and patient’s instructions.
Note the indented statement below is required by the Federal Government Clean Air Act for all products containing chlorofluorocarbons.
A notice similar to the above warning has been placed in the patient instruction leaflet of this package insert pursuant to regulations of the U.S. Environmental Protection Agency (EPA). The patient’s warning states that the patient should consult his or her physician if there are questions about alternatives.
Manufactured for:
IVAX Pharmaceuticals, Inc.
Miami, FL 33137
by:
IVAX Pharmaceuticals Ireland B2
Waterford, Ireland 11/02
Albuterol (Salbutamol)
Albuterol (Salbutamol)
