Салметерола ксинафоат

Uses

Inhaled Салметерола ксинафоат exerts a significant bronchodilating effect within 10 to 20 minutes of single-dose administration with asthma and this effect lasts for up to 12 hours or more. Салметерола ксинафоат has a beneficial effect on airway mucociliary clearance that will reduce the incidence of respiratory tract infections.

Салметерола ксинафоат produces a significant protective effect against Exercise Induced Asthma (EIA) for up to 9 to 12 hours in both adolescents and adults.

Салметерола ксинафоат improves the overnight PEFR (Peak Expiratory Flow Rate) and controls the symptoms of the patients with nocturnal asthma. The use of Салметерола ксинафоат avoids exposure of children to theophylline or high-dose corticosteroid, with their attendants risks.

Addition of Салметерола ксинафоат to inhaled corticosteroid therapy is significantly more effective in terms of an improvement in lung function, symptom control and a reduction in the use of rescue bronchodilator therapy (use of short acting beta2-agonist).

Addition of Салметерола ксинафоат to inhaled corticosteroid therapy also significantly reduces the use of inhaled corticosteroids

Салметерола ксинафоат is also used to associated treatment for these conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD), Exercise-Induced Bronchospasm

How Салметерола ксинафоат works

Beta-2 adrenoceptor stimulation causes relaxation of bronchial smooth muscle, bronchodilation, and increased airflow.

Салметерола ксинафоат is hypothesized to bind to 2 sites on the beta-2 adrenoceptor. The saligenin moiety binds to the active site of the beta-2 adrenoceptor. The hydrophilic tail of salmeterol binds to leucine residues in the exo-site of the beta-2 adrenoceptor almost irreversibly, allowing salmeterol to persist in the active site, which is responsible for it's long duration of action.

Another hypothesis is that the lipophilic drug diffuses into lipid bilayer of smooth muscle cells and provides a depot of drug to the cells over a longer period of time.

Dosage

Салметерола ксинафоат dosage

Inhalation/Respiratory-

Chronic asthma:

• Adult: As metered dose aerosol or dry powder inhaler: 50 mcg bid, or up to 100 mcg bid if necessary, in asthma patients with more severe airways obstruction.
• Child: 4-12 yr 50 mcg bid.

Prophylaxis of exercise-induced asthma:

• Adult: As metered dose aerosol or dry powd inhaler: 50 mcg at least 30 min prior to exercise.
• Child: ≥4 yr Same as adult dose.

Chronic obstructive pulmonary disease:

• Adult: As metered dose aerosol or dry powder inhaler: 50 mcg bid.

Side Effects

Dose related tremor, subjective palpitations and headaches are usually mild and transient. Skin reactions, muscle cramps, non-specific chest pain, local irritation and arthralgia have been reported.

Toxicity

Patients experiencing an overdose have presented with metabolic acidosis, hyperlactatemia, anxiety, palpitations, chest pain, sinus tachycardia, ST depression, hypokalemia, hypophosphatemia. Though patients may also present with seizures, angina, hypertension or hypotension, arrhythmia, headache, tremor, muscle cramps, dry mouth, nausea, dizziness, fatigue, malaise, insomnia, and hyperglycemia. Patients should be given symptomatic and supportive treatment which may include intravenous fluids, potassium supplementation, a cardioselective beta-blocker, and cardiac monitoring.

Data regarding the LD₅₀ of salmeterol is not readily available.

Precaution

Patient with CV disease, CNS disorders, DM, hyperthyroidism, hypokalaemia, seizure disorders, ketoacidosis. Not intended for the relief of acute bronchospasm. Hepatic impairment. Pregnancy and lactation.

Interaction

As with all the other beta2-agonists there may be interaction with betablocking agents at the receptor site when given concomitantly.

Monoamino Oxidase Inhibitors and Tricyclic Antidepressants : These agent should be used with caution because Салметерола ксинафоат may be potentiated by these agents.

Food Interaction

Салметерола ксинафоат Hypertension interaction

[Moderate] Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression).

Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol.

However, beta-2-selectivity is not absolute and can be lost with larger doses.

High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias.

Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and

The recommended dosages should not be exceeded.

Салметерола ксинафоат Drug Interaction

Moderate: duloxetine, escitalopram, budesonide / formoterol, albuterolMinor: fluticasone / salmeterolUnknown: aspirin, aspirin, ipratropium, amoxicillin / clavulanate, celecoxib, rosuvastatin, heparin, atorvastatin, acetaminophen, clopidogrel, montelukast, tiotropium, cyanocobalamin, ascorbic acid, cholecalciferol

Салметерола ксинафоат Disease Interaction

Moderate: cardiovascular, diabetes, hypokalemia, seizures, hepatic dysfunction

Volume of Distribution

In asthmatic patients, the volume of distribution of the central compartment is 177L and the volume of distribution of the peripheral compartment is 3160L.

Elimination Route

In asthmatic patients, a 50µg dose of inhaled salmeterol powder reaches a C_max of 47.897pg/mL, with a T_max of 0.240h, and an AUC of 156.041pg/mL/h.

Half Life

The half life of salmeterol is 5.5h.

Clearance

The average clearance of salmeterol in a group of asthmatic patients was 392L/h. Further data regarding the clearance of salmeterol is not readily available.

Elimination Route

Салметерола ксинафоат is 57.4% eliminated in the feces and 23% in the urine. Less than 5% of a dose is eliminated in the urine as unchanged salmeterol.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Monotherapy in the treatment of asthma. Treatment of status asthmaticus, other acute episodes of asthma or COPD.

Special Warning

Hepatic Impairment: Because Салметерола ксинафоат is extensively metabolised by the liver, patients with hepatic impairment receiving the drug should be closely monitored.

Acute Overdose

Symptoms: Dizziness, HTN or hypotension, tremor, headache, tachycardia, hypokalaemia, seizures, angina, arrhythmias, nervousness, muscle cramps, dry mouth, palpitations, nausea, fatigue, malaise, insomnia, hyperglycaemia, metabolic acidosis.

Management: Symptomatic and supportive treatment. β-blockers may be considered but should be used with caution.

Storage Condition

Store between 20-25° C. Protect from heat or sunlight.

Innovators Monograph

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