Airomir (Salbutamol Sulfate)

AIROMIR™

3M Pharmaceuticals

Salbutamol Sulfate

Bronchodilator – b2-adrenergic Stimulant

Action And Clinical Pharmacology: Salbutamol produces bronchodilation through stimulation of b2-adrenergic receptors in bronchial smooth muscle, thereby causing relaxation of bronchial muscle fibers. This action results in improved pulmonary function as demonstrated by spirometric measurements. At therapeutic doses, salbutamol has little action on the b1-adrenergic receptors in cardiac muscle.

Clinical experience has shown that inhaled salbutamol, like other b-adrenergic agonists, can produce significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure and/or ECG changes. Other effects common to this class of drugs and probably mediated by b-adrenoreceptors are tremor and hypokalemia.

The time to onset of a 15% increase in FEV1 is 5 to 15 minutes after inhalation of salbutamol and the time to peak effect occurs within 60 to 90 minutes. The mean duration of effect as measured by a 15% increase in FEV1 is about 3 hours. In some patients, duration of effect is as long as 6 hours.

Indications And Clinical Uses: For the symptomatic relief and prevention of bronchospasm due to bronchial asthma, chronic bronchitis and other chronic bronchopulmonary disorders in patients in whom reversible bronchospasm is a complicating factor. In addition, salbutamol inhalation aerosol is indicated for the prevention of exercise-induced asthma.

Contra-Indications: In patients hypersensitive to salbutamol or any of the components in the Airomir Inhalation Aerosol. (see Supplied).

Manufacturers’ Warnings In Clinical States: Use of Anti-inflammatory Agents: In accordance with the present practice for asthma treatment, concomitant anti-inflammatory therapy (e.g., corticosteroids) should be part of the regimen if inhaled salbutamol needs to be used on a regular daily basis (see Dosage). It is essential that the physician instruct the patient in the need for further evaluation if the patient’s asthma becomes worse.

Cardiovascular Effects: In individual patients, any b2-adrenergic agonist, including salbutamol, may have a clinically significant cardiac effect. Care should be taken with patients suffering from cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Special care and supervision are required in patients with idiopathic hypertrophic subvalvular aortic stenosis, in whom an increase in the pressure gradient between the left ventricle and the aorta may occur, causing increased strain on the left ventricle.

Paradoxical Bronchospasm: With repeated excessive use of sympathomimetic inhalation preparations, some patients have been reported to have developed severe paradoxical bronchospasm, occasionally leading to death. The cause of either the refractory state or death is unknown. However, it is suspected in the fatal episodes that cardiac arrest occurred following the unexpected development of a severe acute asthmatic crisis and subsequent hypoxia.

Do Not Exceed the Recommended Dose: Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. The exact cause of death is unknown, but cardiac arrest following the unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of salbutamol inhalation aerosol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

Patients with Special Diseases and Conditions: Care should be taken in patients with convulsive disorders, hyperthyroidism, or in patients who are unusually responsive to sympathomimetic amines.

Precautions: General: If salbutamol therapy does not produce a significant improvement or if the patient’s condition worsens, medical advice must be sought to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnea, a physician 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 use of b2-agonists to control symptoms is usually a sign of worsening asthma. In worsening asthma it is inadequate to increase b2-agonist use only, especially over an extended period of time. Instead, a reassessment of the patient’s therapy plan is required and concomitant anti-inflammatory therapy should be considered (see Dosage).

Geriatrics: As with other b2-agonists, special caution should be observed when using salbutamol in elderly patients who have concomitant cardiovascular disease that could be adversely affected by this class of drug.

Children: Safety and effectiveness in children below the age of 6 years have not been established.

Pregnancy: Salbutamol has been in widespread use for many years in human beings without apparent ill consequence. However, there are no adequate or well-controlled studies in pregnant women, and there is little published evidence of its safety in the early stages of human pregnancy. Administration of any drug to pregnant women should only be considered if the anticipated benefits to the expectant woman are greater than any possible risks to the fetus.

A reproduction study in rats was performed with salbutamol inhalation aerosol and no teratogenic effects were observed. Studies of propellant HFA-134a in pregnant rats or rabbits have not shown any specific hazard.

Labor and Delivery: Although there have been no reports concerning the use of salbutamol inhalation aerosol during labor and delivery, 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 aerosol use, it should be kept in mind.

Lactation: Since salbutamol is likely excreted in breast milk, and because of the potential for tumorigenicity shown for salbutamol in 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.

Patients with Special Diseases and Conditions: Large doses of i.v. salbutamol have been reported to aggravate pre-existing diabetes and ketoacidosis. Additionally, b-agonists, including salbutamol given i.v. may cause a decrease in serum potassium possibly through intracellular shunting. The relevance of this observation to the use of salbutamol inhalation aerosol given at the recommended daily dosing is unknown, since the aerosol dose is much lower than doses given i.v.

Drug Interactions: MAO Inhibitors or Tricyclic Antidepressants: Salbutamol should be administered with extreme caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salbutamol on the cardiovascular system may be potentiated.

Other Inhaled Sympathomimetics/Epinephrine: Other inhaled sympathomimetic bronchodilators or epinephrine should not be used concomitantly with salbutamol. If additional adrenergic drugs are to be administered by any route to the patient using inhaled salbutamol, the adrenergic drugs should be used with caution to avoid deleterious cardiovascular effects. Such concomitant use must be individualized and not given on a routine basis. If regular coadministration is required then alternative therapy must be considered.

b-Blockers: b-adrenergic receptor blocking agents, especially the noncardioselective ones, may effectively antagonize the action of salbutamol, and therefore salbutamol and nonselective b-blocking drugs, such as propranolol, should not usually be prescribed together.

Diuretics: The ECG changes and/or hypokalemia which may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by b-agonists, especially when the recommended dose of the b-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of b-agonists with non-potassium sparing diuretics.

Digoxin: Mean decreases of 16 and 22% in serum digoxin levels were demonstrated after single dose i.v. and oral administration of salbutamol, 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 salbutamol and digoxin on a chronic basis is unclear; however, careful evaluation of serum digoxin levels is recommended in patients who are currently receiving digoxin and salbutamol.

Information to be Provided to the Patient: Patients should be advised to always carry their salbutamol inhalation aerosol to use immediately if an episode of asthma is experienced.

See the illustrated Information for the consumer insert that is dispensed with the product.

It is important that patients be instructed on how to use salbutamol inhalation aerosol correctly and how it should be used in relation to other medication they are taking. Patients should be given the following information: The action of salbutamol inhalation aerosol should last for 4 to 6 hours. Salbutamol inhalation aerosol should not be used more frequently than recommended. Do not increase the number of puffs or the frequency of doses of salbutamol inhalation aerosol without consulting your physician. If you find that treatment becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, seek medical attention immediately. While you are taking salbutamol inhalation aerosol, other inhaled drugs should be taken only as directed by your physician. If you are pregnant or nursing, contact your physician about the use of salbutamol inhalation aerosol. You may notice a different taste or spray force with Airomir compared to salbutamol aerosol inhalers that contain CFC propellants.

Common adverse effects of your treatment with inhaled salbutamol include palpitations, chest pain, rapid heart rate, tremor, or nervousness.

Adverse Reactions: A 12-week double-blind study compared Airomir Inhalation Aerosol, Ventolin inhaler (U.S. source), and HFA-134a placebo in 565 asthmatic patients. Table I lists the incidence of all adverse events (whether considered drug related or not related to drug by the investigator) from this study which occurred at a rate of at least 3% in the Airomir Inhalation Aerosol group. Only those adverse events which occurred more frequently in either the Airomir Inhalation Aerosol treatment group or the Ventolin treatment group than the placebo group are listed.

Adverse events reported by less than 3% of the patients receiving Airomir, and by a greater proportion of Airomir Inhalation Aerosol patients than placebo patients, which have the potential to be related to Airomir Inhalation Aerosol include: dysphonia, contact dermatitis, increased sweating, dry mouth, chest pain, edema, rigors, ataxia, leg cramps, hyperkinesia, eructation, flatulence, tinnitus, diabetes mellitus, anxiety, depression, somnolence and rash.

In a small cumulative dose study, tremor, nervousness, and headache appeared to be dose-related. Palpitation has also been observed with Airomir.

Rare cases of urticaria, angioedema, rash, bronchospasm and oropharyngeal edema have been reported after the use of inhaled salbutamol. In addition, salbutamol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vomiting, vertigo, CNS stimulation, insomnia, headache, unusual taste and drying or irritation of the oropharynx.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Manifestations of overdosage may include anginal pain, hypertension, hypokalemia, tremor and tachycardia and exaggeration of other pharmacological effects as listed in Adverse Effects.

As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse.

The oral LD50 in male and female rats and mice was greater than 2 000 mg/kg. The aerosol LD50 could not be determined.

In the event of overdose, supportive therapy should be instituted. Dialysis is not appropriate treatment for overdosage of salbutamol inhalation aerosol. The judicious use of a cardioselective b-receptor blocker is suggested, bearing in mind the danger of inducing an asthmatic attack.

Dosage And Administration: Dosage should be individualized, and the patient’s response should be monitored by the prescribing physician on an ongoing basis.

In accordance with the present practice for asthma treatment, if salbutamol is required for relief of symptoms more than twice a day on a regular daily basis or for an extended period of time, anti-inflammatory therapy (e.g., corticosteroids) should be part of the regimen.

Increasing demand for salbutamol preparations in bronchial asthma is usually a sign of worsening asthma and indicates that the treatment plan should be reviewed.

If a previously effective dose fails to provide the usual relief, or the effects of a dose last for less than 3 hours, patients should seek prompt medical advice since this is usually a sign of worsening asthma.

As there may be adverse effects associated with excessive dosing, the dosage or frequency of administration should only be increased on medical advice. However, if a more severe attack has not been relieved by the usual dose, additional doses may be required. In these cases, patients should immediately consult their doctors or the nearest hospital.

Acute Symptoms: Patients 12 years and older: 1 to 2 inhalations (100 to 200 g). Children (6 to 11 years): 1 inhalation (100 g).

If a more severe attack has not been relieved by the usual dose (1 to 2 inhalations), further inhalations may be required. In these cases, patients should immediately consult their doctors or the nearest hospital.

Intermittent and Long-term Treatment: If despite appropriate maintenance therapy, regular daily use of the inhalation aerosol remains necessary for the control of bronchospasm, the recommended dose is: Patients 12 years and older: 1 to 2 inhalations (100 to 200 g) 3 to 4 times daily, not exceeding 8 inhalations (800 g/day. Children (6 to 11 years): 1 inhalation (100 g), not exceeding 4 inhalations (400 g/day).

Prevention of Exercise-induced Asthma: Patients 12 years and older: 2 inhalations (200 µg) 30 minutes before exertion. The effectiveness of Airomir in preventing exercise-induced asthma in children younger than 12 years of age has not been established.

Total Daily Dose Should Not Exceed: Patients 12 years and older: 8 inhalations (800 µg). Patients 6 to 11 years: 4 inhalations (400 g).

Availability And Storage: Each pressurized inhalation aerosol delivers salbutamol sulfate, USP equivalent to 120 ex-valve g into the mouthpiece of the adapter. Nonmedicinal ingredients: ethanol, oleic acid and propellant HFA-134a. The inhalation aerosol does not contain chlorofluorocarbons (CFCs).

Ethanol has been previously used in inhaled medication, as a cosolvent. The small amounts used in inhalers are not known to cause safety problems in asthmatics. A metered dose from Airomir Inhalation Aerosol delivers 0.0054 mL of ethanol per puff which is subject to evaporation as the aerosol expands and is diluted in body fluids as it expands.

Individual packages of 100- or 200-dose inhalers. The 200-dose product contains a minimum net content weight of 6.7 g and will provide a minimum of 200 inhalations. The 100-dose product (hospital pack) contains a minimum net content weight of 3.7 g and will provide a minimum of 100 inhalations.

Store between 15 and 30°C. Protect from direct sunlight and frost. Prime the inhaler when new and after 2 or more weeks of non-use by discharging a minimum of 4 sprays to the atmosphere. Shake well before using. As the vial is pressurized no attempt should be made to puncture it or dispose of it by burning.

New Product 1998

AIROMIR™ 3M Pharmaceuticals Salbutamol Sulfate Bronchodilator – b2-adrenergic Stimulant

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