Product Monograph - Mylan-Salbutamol Respirator Solution
PRECAUTIONS
If therapy does not produce a significant improvement or if the patient's condition worsens, medical advice must be sought in order to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnea, a doctor should be consulted immediately.
Failure to respond for at least 3 hours to a previously effective dose of salbutamol indicates a deterioration of the condition and the physician should be contacted promptly. Patients should be warned not to exceed the recommended dose.
Increasing the use of β2-agonists is usually a sign of worsening asthma. Under these conditions it is inadequate simply to increase their use in particular over an extended period of time, and a reassessment of the patient's therapy plan is required and concomitant anti-inflammatory therapy should be considered.
To ensure the proper dosage administration of the drug, the patient should be instructed by the physician or other health professional in the proper use of the nebulizer. During inhalation, children should be assisted or supervised by an adult who knows the proper use of the nebulizer.
Use of the respirator solution by means other than nebulization or IPPV is not recommended until the safety and the dosage regimen for alternate methods of delivery have been established.
Drug Interactions: Salbutamol should be administered with extreme caution to patients being treated with MAO inhibitors or tricyclic antidepressants since the action of salbutamol on the cardiovascular system may be potentiated.
The concomitant use of salbutamol and other sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving salbutamol tablets. Such concomitant use, should be individualized, and not given on a routine basis. If regular co-administration is required, this indicates that disease control is suboptimal and alternative therapy should be considered.
Salbutamol and beta-receptor blocking agents inhibit the effect of each other.
A small number of cases of acute angle closure glaucoma have been reported in patients treated with a combination of nebulized salbutamol and ipratropium bromide. A combination of nebulised salbutamol with nebulized anticholinergics should therefore be used cautiously. Patients should receive adequate instruction in correct administration and be warned not to let the solution or mist enter the eye.
Pregnancy: Teratogenic Effects: Administration of drugs during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.
Salbutamol has been in widespread use for many years in human beings without apparent ill consequence; however, as with the majority of drugs, there is little published evidence of its safety in the early stages of human pregnancy; there are no adequate and well-controlled studies in pregnant women. Salbutamol has been shown to be teratogenic in mice when given in doses corresponding to 14 times the human aerosol dose; when given s.c. in doses corresponding to the human nebulization dose; when given s.c. in doses corresponding to 0.2 times the maximum human (child weighing 21 kg) oral dose; and when given s.c. in doses corresponding to 0.4 times the maximum human oral dose.
Labor and Delivery: Salbutamol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It has been reported that high doses of salbutamol administered i.v. inhibit uterine contractions. Although this effect is extremely unlikely as a consequence of the use of inhaled formulations, it should be kept in mind. Oral salbutamol has been shown to delay preterm labor in some reports. There are presently no well-controlled studies which demonstrate that it will stop preterm labor or prevent labor at term. Therefore, cautious use of salbutamol is required in pregnant patients when given for relief of bronchospasm so as to avoid interference with uterine contractibility.
As maternal pulmonary edema has been reported during or following premature labor in patients receiving β2-agonists, careful attention should be given to fluid balance, and cardio-respiratory function should be monitored.
Lactation: As salbutamol is probably secreted in breast milk and because of the potential for tumorigenicity shown 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. It is not known whether salbutamol in breast milk has a harmful effect on the neonate.
ADVERSE REACTIONS
The most frequent adverse reactions are nervousness and tremor. Headache, tension due to effects on skeletal muscle, tachycardia, palpitations, transient muscle cramps, insomnia, nausea, weakness, dizziness and sweating have also been reported. Other rare adverse events have been drowsiness, flushing, restlessness, irritability, chest discomfort, difficulty in micturition, hypertension, angina, vomiting, vertigo, central nervous stimulation, unusual taste and drying or irritation of the oropharynx.
As with other β2-agonists, hyperactivity has been reported rarely in children.
Potentially serious hypokalemia may result from β2-agonist therapy, mainly from parenteral and nebulized administration.
Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension, rash, oropharyngeal edema and collapse have been reported very rarely.
As with other inhalation therapy, the potential for paradoxical bronchospasm should be kept in mind. If it occurs, the preparation should be discontinued immediately and alternative therapy instituted.
SYMPTOMS AND TREATMENT OF OVERDOSAGE
Overdosage may cause tachycardia, cardiac arrhythmia, hypokalemia, hypertension and, in extreme cases, sudden death. In order to antagonize the effect of salbutamol, the judicious use of a cardioselective beta-adrenergic blocking agent (e.g. metoprolol, atenolol), may be considered, bearing in mind the danger of inducing an asthmatic attack. Serum potassium levels should be monitored.
DOSAGE AND ADMINISTRATION
Dosage should be individualized, and patient response should be monitored by the prescribing physician on an ongoing basis.
If a previously effective dose fails to provide the usual relief, or if the effects of a dose last for less than three hours, patients should seek medical advice immediately since this is usually a sign of seriously worsening asthma.
In accordance with the present practice for asthma treatment, concomitant anti-inflammatory therapy should be part of the regimen if salbutamol respirator solution needs to be used on a regular daily basis.
Adults: The average dose for a single treatment is 2.5 mg to 5 mg Salbutamol up to 4 times daily.
Children: 5 to 12 years: The average dose for a single treatment is 1.25 to 2.5 mg Salbutamol. (See PHARMACEUTICAL INFORMATION).
For more refractory cases, the single dose may be increased to 5 mg of salbutamol. Treatment may be repeated 4 times a day, if necessary.
If a more severe attack has not been relieved by a treatment, further treatment may be required. In these cases, patients should immediately consult their doctor or the nearest hospital. Increasing demand for salbutamol respirator solution in bronchial asthma is usually a sign of worsening asthma and indicates that the treatment plan should be reviewed.
Mylan-Salbutamol Respirator Solution is to be used with a respirator or nebulizer, only under the direction of a physician.
PHARMACEUTICAL INFORMATION
Drug Substance:
Proper Name: Salbutamol sulphate
Chemical Name: 1,3-Benzenedimethanol, "1-[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-sulfate.
Chemical Structure:
Molecular Formula: C26H44N2O10S
Molecular Weight: 576.7
Description: A white odourless powder soluble 1:4 in water and slightly soluble in alcohol, chloroform, and ether. pH=5.8 (1% solution)
Composition:
Mylan-Salbutamol Respirator Solution is a sterile solution containing salbutamol sulphate equivalent to 5 mg of salbutamol base per mL. The solution is preserved with benzalkonium chloride 0.01% w/v (5 mg/mL). The pH is adjusted with sulfuric acid.
Stability and Storage Recommendations:
Store between 15˚ and 25˚C. Protect from light.
In hospitals, diluted Mylan-Salbutamol Respirator Solution (5 mg/mL), usually 1:5 or 1:10, with Sterile 5% Dextrose, or Sterile Normal Saline, should be used within 24 hours from time of dilution when stored at room temperature or within 48 hours when stored under refrigeration.
In the home, Mylan-Salbutamol Respirator Solution (5 mg/mL) should be diluted with Sterile Normal Saline immediately before use.
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Special Instructions:
Mylan-Salbutamol Respirator Solution can be used by 2 methods:
- 1) Nebulization.
- 2) Intermittent positive pressure ventilation.
Nebulization
When used in a nebulizer, a mouthpiece or a face mask may be applied. The nebulizer should be connected to a compressed air or oxygen pump. Gas flow should be approximately 6 to 10 L/minute. With an average volume of 3 mL, a single treatment lasts approximately 10 minutes. It is advisable to prepare one dose at a time.
In hospitals, diluted Mylan-Salbutamol Respirator Solution (5 mg/mL), usually 1:5 or 1:10, with Sterile Normal Saline, should be used within 24 hours from time of dilution when stored at room temperature or within 48 hours when stored under refrigeration.
Diluents containing preservatives are not recommended as the safety of preservatives have not been established for inhalation therapy.
Cleansing and maintenance of the nebulizer must be carefully followed according to the manufacturer's instructions.
Intermittent positive pressure ventilation
When administered through intermittent positive pressure ventilation, the inspiratory pressure is usually 10-20 cm H20 and the duration of administration varies from 5 to 20 minutes, depending upon the patient and the control of the apparatus. This length of administration provides a more gradual and more complete lysis of bronchospasm. It has been reported that the use of intermittent positive pressure ventilation in acute asthma attacks, in several cases was related to lethal episodes of hypoxia and pneumothorax. This method of drug administration may be ineffective in patients with severe obstruction and greatly increased airway resistance and it may induce severe hypercapnia and hypoxia.
During intermittent positive pressure ventilation therapy, the monitoring of arterial blood gases is highly desirable.
AVAILABILITY OF DOSAGE FORMS
Sterile Mylan-Salbutamol Respirator Solution contains salbutamol sulphate equivalent to 5 mg of salbutamol base per mL. The 5 mg/mL solution is preserved with benzalkonium chloride 0.01% w/v, and is available in glass containers of 10 mL.