Singulair 4mg Organon prophylaxis and treatment of chronic bronchial asthma (2 blisters x 14 tablets)

Cyslt type 1 receptors (CYSLT1) are found in human airfields, including smooth muscle cells and macrophages of the airway and in other inflammatory cells (including EOSIN leukemia and some bone marrow stem cells). CYSLT is associated with the pathogenesis of asthma and allergic rhinitis. In asthma, the intermediate effects of Leukotriene include a number of effects on the airway, such as bronchospasm, mucus secretion, increased capillary permeability and mobilizing eosin blood cells. In allergic rhinitis, CYSLT is secreted from the nasal mucosa after exposure to allergens in the reactions in fast and slow phases and is related to allergic rhinitis symptoms. CYSLT in the nose will increase the obstruction of the airway and congestion symptoms.

Montelukast oral form is anti -inflammatory substance, improving inflammatory parameters in asthma. Based on biochemical and pharmacological tests, Montelukast proves high affinity and selective selection with CYSLT receptor (this effect is superior to other receptors that are also important in pharmacological, such as Prostanoid, Cholinergic or β-Adrenergic). Montelukast strongly inhibits the physiological effects of LTC4, LTD4, LTE4 at CYSLT1 receptor without the effect of march.

In asthma patients, Montelukast inhibits the cysteinyl leucotriene receptors in the airway proving through the ability to inhibit the bronchospasm of Ltd4 inhalation with doses of less than 5 mg, which has been clasped the bronchial spasm caused by LTD4 Montelukast causing bronchiectasis for 2 hours after drinking; These effects are coordinated with bronchodilators by using the agonist β.

Clinical research in asthma

In clinical studies, Singulair takes effect in adults and children to prevent and treat chronic asthma, including preventing bronchospasm due to exercise.

Singulair is valid when used separately or when combined with other drugs in the prescription to treat chronic asthma. Singulair can be coordinated with inhaled corticosteroids, which will have a synergistic effect to control asthma or to reduce the dose of inhaled corticosteroids while maintaining clinical stability.

People aged 15 and over

In two double blind studies, 12 weeks, with a control, similarly designed, in patients aged 15 and older with asthma, using Singulair to take 1 dose per dose 10 mg in the evening, showing significant improvement in asthma control parameters through asthma symptoms, consequences of asthma, respiratory function and "need" use of agonized substances.

Singulair significantly improves daytime symptoms of the patient's report and wake up at night, compared to Placebo. The specific consequences of asthma, including the appearance of asthma attacks, need the help of corticosteroids, stop the drug due to asthma attacks worse, asthma drama and the number of days from asthma are improved compared to Placeboo. The overall assessment of doctors and patients on asthma, as well as specific quality of life quality assessments with asthma (in all fields, including normal daily activities and asthma symptoms) are significantly better than in the control group. Singulair significantly improves exhalation volume in the first second in the morning (FEV1), the maximum breathing speed in the morning and afternoon (PEFR) and also reduces the demand for agonized drugs β when compared to Placebo.

The treatment effect is usually achieved after the first dose and maintained for about 24 hours. The effectiveness of treatment is also stable when used continuously once a day in tests lasting up to 1 year.

Stop the drug after using Singulair for 12 weeks without causing reverse reaction, causing worse asthma.

Comparison with inhaled Beclomethasone (each time 200 µg, 2 times daily with diffuse tools), sees Singulair has a faster initial response, although through a 12 -week study, Beclomethasone has a larger average treatment effect. However, the group using Singulair has a high percentage of clinical meetings equivalent to the inhaled Beclomethasone.

Children from 6 years old to 14 years old

Children 6-14 years old, using a 5 mg chewing tablet in the evening, significantly reducing the drama of asthma, improving the evaluation of specific quality of life due to asthma, compared to Placebo. Singulair also improves the morning FEV1, reduces the total "need" of the day of the daily owner β.

The treatment effect is achieved after the first dose and stable up to 6 months of continuous use, once a day.

growth in children with asthma

Two control clinical studies show that Montelukast does not affect the ability to develop the body in children before puberty has asthma. In a study in children from 6 years old to 11 years old, the body development is assessed by the growth of the leg length, the group using Montelukast 5 mg once a day for 3 weeks of results is similar to the placebo group, and in the group using Budesonide in the form of gas (200 µg twice a day) for 3 weeks is lower than a statistical way compared to the placebo group. In a 56 -week study in children from 6 to 8 years of age, the growing chart in children using Montelukast 5 mg once a day is similar to the placebo group (the average LS value for Montelukast and the regard for the corresponding place: 5.67 and 5.64 cm/year), and in the group using Beclomethasone when used (200 µg, twice a day), this value is lower than the average value. 4.86 cm/year) in children using aerosol, compared to the placebo group [Different difference in the average LS (with 95%reliability) is: -0.78 (-1.06; -0.49) cm/year). Both Montelukast and Beclomethasone give clinical benefits in the treatment of mild asthma patients in a significant way compared to the placebo group.

Children from 6 months to 5 years old

In the 12-week study, the control of Placebo in children 2-5 years old, giving Singulair once a day 4 mg, improved sustainably asthma control parameters, regardless of treatment in combination with asthma vaccine, compared to Placebo. 60% of patients do not use other asthma control treatment. Singulair improves daytime symptoms (including them, wheezing, breathing disorders and restricting activity) and night symptoms when compared to Placebo. Singulair also significantly reduces the "demand" of agonized drugs β and corticosteroids for emergency compared to Placebo. Patients using Singulair have more and more asthma that is statistically significant compared to the patient in the Placebo group. Treatment effect immediately after the first dose.

Singulair's effectiveness in children from 6 months to 2 years of age is extracted from results in children over 2 years of age with asthma and based on similar dynamic pharmacokinetics as well as on the pathology, pathophysiology and the effect of the drug basically equivalent when comparing the two age groups above.

For patients with corticosteroids inhaled inhalation

Separated studies in adults show that Singulair is used in combination with inhaled corticosteroids that have a clinical coordinates and allows a decrease in steroid dose when used in combination. In the study with the control of Placebo, the patient starts to use inhaled corticosteroids at a dose of about 1600 kg a day, during the use of Placebo, the rate of steroid use has been reduced by about 37%. Moreover, Singular also helps reduce 47% of inhaled corticosteroid dose compared to 30% in the Placebo group. In another study, Singulair brings clinical benefits plus the maintenance objects but is not controlled appropriately with inhaled corticosteroids (daily use 400UG Beclomethasone).

completely and suddenly beclomethasone in patients used to combine Singulair with Beclomethasone causing clinical harm in some cases, proving that the drug stopped gradually with tolerance rather than a sudden stop. For people who are sensitive to aspirin, most of them are when combined with corticosteroids with inhaled and oral forms, Singulair has improved significantly on asthma control parameters.

For patients with bronchospasm due to exertion

Singulair takes 10 mg once a day will prevent bronchospasm due to exertion in people aged 15 and older. In a 12 -week study, Singulair showed significant inhibition of the level and time of reducing FEV1 more than 60 minutes after exertion, the percentage of the maximum FEV1 reduction after exertion and 5% recovery time of FEV1 before exertion. This protective effect is a constant during the treatment process, proving that there is no familiar trait. In a separate diagonal study, this protective effect is achieved after 2 days of taking the drug, drinking once a day. For children 6-14 years old, giving 5 mg chewing tablets, in a similar cross-out study, it also feels protective effects as in adults and this protection is maintained throughout the dose distance (24 hours).

Effects on inflammation in asthma

In clinical studies, Singulair has been shown to inhibit both bronchospasm in early phase and late phase due to allergens. Because inflammatory cell infection (Eosin -like leukemia) is an important characteristic of asthma, surveyed Singulair's effects on eucalyptus loves EOSIN in peripheral blood and airway. In clinical studies in the ILB/III phase, Singulair shows a significant reduction in eosin leukemia in peripheral blood, down 15% compared to the starting and compared to Placeboo. In children from 6 to 14 years old, Singulair reduces Eosin leukemia in peripheral blood 13% over 8 weeks of treatment compared to the Placebo group. Singulair also significantly reduces Eosin leukemia in the airway, in sputum compared to the Placebo group. In this study, the amount of eosinophilia liked the peripheral blood and the clinical assessment criteria for asthma improvement in the treatment group with Singulair.

Clinical research-allergic nose

Singulair's effectiveness in the treatment of seasonal allergic rhinitis is studied in random, double -blind, 2 -week -long trials, with a control of Placebo, over 4924 patients (there are 1751 Singulair users). Patients aged 15 years and older, have a history of seasonal allergic rhinitis, positive skin tests in at least one season of allergens and have obvious symptoms of seasonal allergic rhinitis at the beginning of the study.

In a combination analysis of 3 key studies, using 10 mg Singulair for 1189 patients (once a day in the evening), significantly improving the main targets, the index of the nose during the day and clinical manifestations (such as nose congestion, nose, nose, steam itching); The index of night symptoms (such as nasal congestion, difficulty sleeping, waking up many times at night); The summary index of symptoms (including both day and night nasal symptoms); And through the general assessment of the patient and the doctor about allergic rhinitis compared to Placebo.

In another 4 -week study, Singulair once a day in the morning shows a significant stronger in the first 2 weeks compared to Placebo and is in line with the effect of the dose -taking studies in the evening. Moreover, valid through all 4 weeks is also consistent with the results of 2 weeks.

For patients over 15 years old with seasonal allergic rhinitis, Singulair shows an average of 13% of eosin leukemia in peripheral blood compared to Placeboo, through dual blind treatment periods.

Singulair's effectiveness of allergic rhinitis all year round was studied in two studies with pot control, similar design, randomly divided, double blindness lasting 6 weeks, over 3235 patients (of which 1632 Singulair users). The age of the patient is 15-82 years of age with a history of allergic rhinitis all year round, skin testing positive for allergens year-round (including housewares, animal hairs, mold spores) and have outstanding symptoms of allergic rhinitis all year round at the beginning of treatment.

In one study, Singulair 10 mg used 1 time daily for 1000 patients to be significantly improved in terms of the main criteria, the indicators of the nasal nasal symptoms (nose bleeding, runny nose, sneezing) compared to Placeboo. Singulair also shows improvement in allergic rhinitis through the patient's assessment as stated in the auxiliary criteria for global assessment of allergic rhinitis symptoms by patients, and the overall assessment of life quality in conjunctivitis (average score of 7 fields of activity: sleep, non-mosaic symptoms/air-air, issues in practice, nose symptoms, comparison).

Singulair's effectiveness in the treatment of seasonal allergic rhinitis 2-14 years old and in the treatment of allergic rhinitis all year round in children 6 months -14 years old is proven by extracurricular from the effect of this drug in the 215 -year -old patient with allergic rhinitis along with the assumption that the disease, pathology and the effect of the drug are basically the same in these populations.

Dynamic pharmacokinetics

absorption

After drinking, Montelukast absorbed quickly and almost completely. With 10 mg film tablets, CMAX concentration reaches 3 hours (TMAX) after taking adults, taking medicine when hungry. Born when taking oral medication is 64%. Birth and cmax are not affected by a standard meal.

With 5 mg chewing tablets, cmax reaches 2 hours after adults drinking. Born when drinking is 37%. Food does not have a great influence in clinical when taking long -term drugs.

With 4 mg chewing tablets, CMAX concentration reaches 2 hours after taking 2-5 years old, taking medicine at hunger.

4 mg oral nuggets are biological equivalent with 4 mg pellets when used for adults when hungry. The use of Montelukast in the form of grain nuggets with apple sauce or during a standard meal does not significantly affect the pharmacokinetics of the drug determined by the area under the AUC curve (1225.7 compared to 1223.1 ng-ml/ml with or without apple sauce and 1191.8 compared to 1148.5 ng-ml/ml with or without standard meals).

Effect and safety have been shown through clinical studies, when using 4 mg chewing tablets, 5 mg chewing tablets, 10 mg film tablets, orally, regardless of meal time. The safety of Singulair is also proven in clinical research for drinking 4 mg grain nuggets without including meal time.

distribution

more than 99% Montelukast binds to plasma proteins. The distribution volume (VD) in the stable state of Montelukast is 8-11 liters. Research on rats with Montelukast marks that the drug is very little distributed through the bloody brain barrier. Moreover, the concentration of the marker after drinking 24 hours is at least in all other tissues.

Metabolism

Montelukast metabolizes very strongly. In studies with treatment dose, plasma concentrations of Montelukast's metabolites are not found in a stable state in adults and children.

In vitro research, using human liver microsome, showing that Cytochrome P450 3A, and 2C, catalyst for Montelukast's metabolism. Based on other results in vitro on human liver microsome, seeing the concentration of Montelukast's treatment in plasma does not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6.

Elimination

Montelukast's purification in plasma is 45 ml/minute in healthy adults. After taking Montelukast, 86% of the markers are found in the feces of a total of 5 days and less than 0.2% discharged through the urine. This, along with the bioavailability of Montelukast oral, shows that Montelukast and the metabolites of the drug are almost entirely through the bile.

In many studies, Montelukast's plasma sale time is 2.7-5.5 hours in healthy young people. Montelukast's pharmacokinetics almost linear when taken to a dose of 50 mg. There is no difference in pharmacokinetics when taking medicine in the morning or evening. When taking 10 mg Montelukast once a day, very little maxtelukast's mother in plasma (approximately 14%).

Patient characteristics

No dose adjustments for older patients, patients with renal impairment or mild to moderate liver failure. There is no clinical evidence in patients with severe liver failure (Child-Pugh> 9).

Dosage for children 6-14 years old is a chewing 5 mg.

Children 2-5 years old with asthma and/or allergic rhinitis

Dosage for children 2-5 years old is a chewing 4 mg.

Singulair 10 mg, the form of film bags available for adults and children over 15 years old.

Singuliar 4 mg, the form of nuggets available as an alternative product for patients from 2 years old - 5 years old.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What do

do when overdose? In chronic asthma studies, Singulair is used daily doses to 200 mg for adults for 22 weeks and short -term research with a dose of up to 900 mg daily, used for about a week, there is no clinical important reaction.

There are also reports on acute poisoning after bringing the drug to the market and in clinical studies with Singulair. These reports include both children and adults with the highest doses of up to 1000 mg. The results of the laboratory and clinical room are in line with the overview of the safety of adults and children. In most overdose reports, no harmful reactions. The most common reactions are similar to Singulair's safety properties including abdominal pain, drowsiness, thirst, headache, vomiting and excitement.Unknown Montelukast can be separated through the peritoneal or dialysis.

In case of emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Notify the physician with unwanted effects when using the drug.