ALBUTEROL SULFATE — albuterol sulfate syrup
Actavis Pharma, Inc.
Albuterol Sulfate Syrup contains albuterol sulfate, USP, the racemic form of albuterol and a relatively selective beta2 -adrenergic bronchodilator. 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:
(C13 H21 NO3 ) •H2 SO4 M.W. 576.7
Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol.
The World Health Organization recommended name for albuterol base is salbutamol.
Albuterol Sulfate Syrup for oral administration contains 2 mg of albuterol as 2.4 mg of albuterol sulfate in each teaspoonful (5 mL). Albuterol Sulfate Syrup also contains the inactive ingredients citric acid, FD&C Yellow #6, flavor enhancer, hypromellose, propylene glycol, purified water, sodium benzoate, sodium citrate, strawberry flavor. Sodium hydroxide may be added to adjust pH.
The pH of the syrup is 3.5 to 4.5.
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.
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.
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.
Albuterol is rapidly absorbed after oral administration of 10 mL of albuterol sulfate syrup (4 mg of albuterol) in normal volunteers. Maximum plasma concentrations of about 18 ng/mL of albuterol are achieved within 2 hours, and the drug is eliminated with a half-life of about 5 hours.
In other studies, the analysis of urine samples of patients given 8 mg of tritiated albuterol orally showed that 76% of the dose was excreted over three days, with the majority of the dose being excreted within the first 24 hours. Sixty percent of this radioactivity was shown to be the metabolite. Feces collected over this period contained 4% of the administered dose.
In controlled clinical trials in patients with asthma, the onset of improvement in pulmonary function, as measured by maximum midexpiratory flow rate (MMEF) and forced expiratory volume in 1 second (FEV1 ), was within 30 minutes after a dose of albuterol sulfate syrup, with peak improvement occurring between 2 and 3 hours. In a controlled clinical trial involving 55 children, clinically significant improvement (defined as maintaining a 15% or more increase in FEV1 and a 20% or more increase in MMEF over baseline values) continued to be recorded up to 6 hours. No decrease in the effectiveness was reported in one uncontrolled study of 32 children who took albuterol sulfate syrup for a 3-month period.
Albuterol Sulfate Syrup is indicated for the relief of bronchospasm in adults and children 2 years of age and older with reversible obstructive airway disease.
Albuterol Sulfate Syrup is contraindicated in patients with a history of hypersensitivity to albuterol or any of its components.
Albuterol Sulfate Syrup, 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 syrup 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 Syrup, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
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 syrup 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.
Albuterol Sulfate Syrup can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, albuterol sulfate syrup should be discontinued immediately and alternative therapy instituted.
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.
Immediate hypersensitivity reactions may occur after administration of albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. Albuterol, like other beta-adrenergic agonists, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. Rarely, erythema multiforme and Stevens-Johnson syndrome have been associated with the administration of albuterol sulfate in children.
Albuterol, 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 have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol 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.
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