Asthlon

Pharmacologic Classification: Corticosteroid.
Pharmacology: Pharmacokinetics: Absorption: The estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th. In adults the systemic bioavailability of budesonide following administration of Budesonide suspension for nebulization via nebulizer is approximately 15% of the declared dose and 40-70% of the dose delivered to the patient. A small part of the systematically available dose comes from inhalation suspension that is allowed. The peak plasma concentration following administration of a single dose of 2 mg is achieved 10-30 minutes after the beginning of inhalation and is approximately 4 nmol/L. In children (4-6 years), the systemic bioavailability of budesonide after administration of Budesonide suspension for nebulization via nebulizer is approximately 6% of the declared dose and 26% of the dose administered to the patient. The peak plasma concentration following administration of a single dose of 1 mg is approximately 20 minutes after the beginning of inhalation and is approximately 2.4 nmol/L.
Distribution: The volume of distribution in adults is approximately 3 L/kg. Plasma protein binding is approximately 85-90%.
Metabolism: Budesonide undergoes extensive (90%) first pass biotransformation in the liver via CYP3A4 to metabolites a low glucocorticosteroid activity. The in-vitro activity of the main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
Excretion: The metabolites are excreted in unchanged or conjugated form predominantly via the kidneys. No unchanged budesonide is found in the urine. Budesonide has a high systemic clearance (approximately 1.2 liters/min) in healthy adults, and the elimination half-life following intravenous administration is approximately 2-3 hours. Budesonide has a systemic clearance of approximately 0.5 L/min in 4 to 6 year-old asthmatic children. Children have an approximately 50% higher clearance per kg body weight than adults. The half-life of budesonide following inhalation is about 2.3 hours in asthmatic children, which is roughly the same as in healthy adults.
Biotransformation: The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of CYP450.
Pharmacodynamics: Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect.
Topical anti-inflammatory effect: The exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions involving T cells, eosinophils and mast cells, such as inhibition of inflammatory mediator release and inhibition of cytokine-mediated immune response are probably important. The intrinsic potency of budesonide, measured as the affinity to the glucocorticoid receptor, is about 15 times higher than that of prednisolone.
A clinical study in asthmatics comparing inhaled and oral budesonide at similar plasma concentrations demonstrated statistically significant evidence of efficacy with inhaled but not oral budesonide compared with placebo. Thus, the therapeutic effect of conventional doses of inhaled budesonide may be largely explained by its direct action on the respiratory tract.
Budesonide has shown anti-anaphylactic and anti-inflammatory effects in provocation studies in animals and patients, manifested as decreased bronchial obstruction in the immediate as well as the late allergic reaction.
Exacerbations of asthma: Inhaled budesonide has been shown to effectively treat and prevent exacerbations of asthma in both children and adults.
Exercise-induced asthma: Therapy with inhaled budesonide, administered either as once or twice daily has been effective when used for prevention of exercise-induced bronchoconstriction. Budesonide has been shown to decrease airway reactivity to histamine and methacholine in hyperreactive patients.
Exacerbations of COPD: Several studies on nebulised budesonide, 4-8 mg/day has shown to effectively treat exacerbations of COPD.

Budesonide nebulizing suspension is indicated for patients with bronchial asthma who require maintenance treatment with glucocorticosteroids for control of the underlying airway inflammation.

Administration can be once or twice daily. Once daily administration can be used for daily doses of 250 mcg-1000 mcg.
Recommended initial dose: Adults/Elderly: 1000 mcg-2000 mcg total daily dose.
Children 12 years and older: Dosage for adults.
Children 6 months to 12 years: 250 mcg-500 mcg total daily dose.
Once daily dosing: Once daily dosing may be considered both in adult and pediatric patients, who require a maintenance dose of 250 mcg to 1000 mcg budesonide per day.
Once daily administration can be initiated both in noncorticosteroid treated patients and in patients well-controlled by inhaled glucocorticosteroids. The dose can be administered either in the morning or in the evening. If deterioration of asthma occurs, the dose should be increased and divided over the day as necessary.
Dose division and miscibility: Budesonide nebulizing Suspension can be mixed with 0.9% saline and with solutions for nebulization of terbutaline, salbutamol, fenoterol, acetylcysteine, sodium cromoglycate or ipratropium. The admixture should be used within 30 minutes. Single dose units can be divided, to allow dose adjustments. The single dose unit is marked with a line (Budesonide Nebulizing Suspension 250 mcg/mL and 500 mcg/mL only). This line indicates the 1 mL volume when the single dose unit is held up-side down. If only 1 mL is to be used, empty the contents until the surface of the liquid reaches the indicator line. Store the opened single dose unit in the envelope, protected from light. Open single dose units should be used within 12 hours.
Direction for Use: Shake well before use. Asthlon should be administered via a nebulizer equipped with a mouthpiece or suitable face mask.
To minimize the risk of oropharyngeal candida infection, the patient should rinse their mouth out with water after inhaling.
Wash the facial skin with water after using the face mask to prevent irritation and maintain nebulizer according to manufacturer's instructions.

History of hypersensitivity to budesonide or any of the ingredients.

Budesonide nebulizing suspension is not intended for rapid relief acute episodes of asthma where an inhaled short-acting bronchodilator is required. If patients find short-acting bronchodilators treatment ineffective, or they need more inhalations than usual, medical attention must be sought. In this situation, consideration should be given to the need for increased anti-inflammatory therapy, e.g. higher doses of inhaled budesonide or a course of oral glucocorticosteroid.
Reduced liver function may affect the elimination of corticosteroids. This may be clinically relevant in patients with severely compromised liver function.
In vivo studies have shown that oral administration of ketoconazole and itraconazole (known inhibitors of CYP3A4 activity in the liver and in the intestinal mucosa) may cause an increase of the systemic exposure to budesonide.
The long term local and systemic effects of Budesonide Nebulizing Suspension in man are not completely known. The dose should be titrated to the lowest effective maintenance dose once control of asthma is achieved. Physicians should closely monitor the growth of children taking corticosteroids by any route and weigh the benefit of corticosteroid therapy and asthma control against the possibility of growth suppression.
Budesonide does not affect the ability to drive and use machines.

Pregnancy: Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies shown an adverse effect (other than decrease in fertility) that was not confirmed in controlled studies in women in the 1 trimester (and there is no evidence of a risk in later trimesters).
Lactation: Budesonide is excreted in breast milk. The administration of Budesonide to women who are breast feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

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Budesonide has not been observed to interact with any drug used for the treatment of rhinitis or asthma. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of CYP450. Inhibitors of this enzyme, e.g. Ketoconazole, can therefore increase systemic exposure to budesonide. However, the use of ketoconazole concomitant with Budesonide Aqueous Nasal Spray for shorter periods is of limited clinical importance. At recommended doses, cimetidine has a slight but clinically insignificant effect on the pharmacokinetics of oral budesonide.

Store at temperatures not exceeding 30°C. Protect from light.

Antiasthmatic & COPD Preparations

R03BA02 - budesonide ; Belongs to the class of other inhalants used in the treatment of obstructive airway diseases, glucocorticoids.

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