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Product
Anti-asthmatic Products (Asthalin Inhaler)
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Anti-asthmatic Products (Asthalin Inhaler)
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Asthalin Inhaler
Salbutamol Sulphate Inhaler
COMPOSITION
ASTHALIN Inhaler
Each actuation delivers:
Salbutamol Sulphate IP equivalent to Salbutamol IP …….100 mcg
Suspended in propellant HFA 134a……………………q.s.
DOSAGE FORM
Inhalation aerosol
PHARMACOLOGY
Pharmacodynamics
In vitro studies and in vivo pharmacologic studies have demonstrated that salbutamol has a preferential effect on beta 2 -adrenergic receptors compared with isoproterenol. While it is recognized that beta 2 -adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta 2 -receptors in the human heart existing in a concentration between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors has not been established. |
Activation of beta 2 -adrenergic receptors on airway smooth muscle leads to the activation of adenyl cyclase and to an increase in the intracellular concentration of cyclic-3`,5`-adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Salbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Salbutamol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.
In most controlled clinical trials, salbutamol has been shown 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 salbutamol, like other beta-adrenergic agonist drugs, can produce significant cardiovascular effects in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes
Pharmacokinetics
The systemic levels of salbutamol are low after inhalation of recommended doses. A study conducted in 12 healthy male and female subjects using a higher dose (1,080 mcg of salbutamol base) showed that mean peak plasma concentrations of approximately 3 ng/mL occurred after dosing when salbutamol was delivered using propellant HFA-134a. The mean time to peak concentrations (t max) was delayed after administration of salbutamol HFA (t max = 0.42 hours) as compared to CFC-propelled salbutamol inhaler (t max = 0.17 hours). Apparent terminal plasma half-life of salbutamol is approximately 4.6 hours. No further pharmacokinetic studies for salbutamol HFA were conducted in neonates, children, or elderly subjects.
Pharmacodynamics
Levosalbutamol:
Levosalbutamol leads to activation of beta 2 -adrenergic receptors on airways smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of cAMP. The increase in cAMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation and bronchodilation. Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cAMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways.
Beclomethasone dipropionate :
The precise mechanisms of glucocorticoid action in asthma are unknown. Inflammation is recognized as an important component in the pathogenesis of asthma. Glucocorticoids have been shown to inhibit multiple cell types (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and mediator production or secretion (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in the asthmatic response. These anti-inflammatory actions of glucocorticoids may contribute to their efficacy in asthma.
INDICATIONS
ASTHALIN Inhaler is indicated in the treatment of bron¬chospasm in bronchial asthma, chronic bronchitis and emphysema, and prophylaxis of exercise–induced asthma.
ASTHALIN Inhaler may be used with a Cipla Spacer/Zerostat Spacer device by patients who find it difficult to synchronize aerosol actuation with inspiration of breath. The Cipla Baby Mask device may be used to facilitate administration to children less than 5 years of age.
DOSAGE AND ADMINISTRATION
For relief of acute episodes of bronchospasm:
Adults :
1 or 2 puffs as necessary.
The maximum dose is up to 8 puffs in 24 hours.
Children:
Half the adult dose.
To prevent allergen- or exercise-induced bronchospasm:
Adults:
Two inhalations, 15 minutes prior to exercise or exposure to allergen.
The maximum dose is 2 puffs, up to 4 times a day.
Children:
Half the adult dose.
WARNINGS AND PRECAUTIONS
Paradoxical Bronchospasm
Inhaled salbutamol sulphate can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, ASTHALIN Inhaler 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.
Cardiovascular Effects
ASTHALIN HFA , like all other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of ASTHALIN Inhaler 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, ASTHALIN HFA , like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
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 ASTHALIN than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and treatment regimen, with special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
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, to the therapeutic regimen.
Immediate Hypersensitivity Reactions
Immediate hypersensitivity reactions may occur after administration of salbutamol sulphate inhalation aerosol, as demonstrated by cases of urticaria, angio-oedema, rash, bronchospasm, anaphylaxis, and oropharyngeal oedema.
Do Not Exceed Recommended Dose
Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.
Drug Interactions
ASTHALIN preparations should be used with caution in patients suffering from thyrotoxicosis. ASTHALIN and non-selective beta-blocking drugs such as propranolol should generally not be prescribed together.
Potentially serious hypokalaemia may result from beta 2 -agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by con-comitant treatment with xanthine deriva¬tives, steroids, diuretics, and by hypoxia. It is recommended that serum potassium levels be monitored in such situations.
Pregnancy
Administration of the drug during preg¬nancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
Lactation
As salbutamol is probably secreted in breast milk, its use by lactating mothers requires careful consideration.
UNDESIRABLE EFFECTS
Mild tremor, hypokalaemia, palpitations, muscle cramps, oropharyngeal irritation, and headache have been rarely reported. These usually disappear with continued treatment. Paradoxical bronchospasm may occur, in which case, the therapy should be discontinued immediately and alter¬native therapy instituted.
OVERDOSAGE
The expected symptoms of overdosage are those of excessive beta-adrenergic stimulation, viz., seizures, angina, hypertension or hypotension, tachycardia (with rates up to 200 beats/min), arrhythmias, nervousness, and fatigue. Cardiac arrest and, even, death is associated with the abuse of ASTHALIN Inhaler .
SHELF-LIFE
3 years
STORAGE AND HANDLING INSTRUCTIONS
Store below 30°C. Do not freeze
PACKAGING INFORMATION
ASTHALIN Inhaler ...................................................Canister containing 200 metered doses
ASTHALIN ECOPACK INHALER .........................Canister containing 400 metered doses
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