MSD SHUNERNING Montelukast Sodium Chewable Tablets For Children's Allergies 5mg*5

[Drug Name]
Generic Name: Montelukast Sodium Chewable Tablets
Trade Name: Singulair
English Name: Montelukast Sodium Chewable Tablets
Chinese Pinyin: Menglusitena Zujuepian

[Ingredients]
The main ingredient of this product is montelukast sodium. Chemical Name: [R-(E)]-1-ff[1-[3-[2-[7-chloro-2-quinolinyl)vinyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid sodium Molecular Formula: C35H3sC1NNa03S Molecular Weight: 608.18

[Properties]
This product is a pink, round tablet.

[Indications]
1. This product is indicated for the prevention and long-term treatment of asthma in children aged 2 to 14 years, including the prevention of daytime and nighttime asthma symptoms, the treatment of aspirin-sensitive asthma, and the prevention of exercise-induced bronchoconstriction. 2. This product is indicated for the relief of symptoms caused by allergic rhinitis (seasonal allergic rhinitis and perennial allergic rhinitis in children aged 2 to 14 years).

[Dosage and Administration]
Once daily. Patients with asthma should take the drug at bedtime. Patients with seasonal allergic rhinitis may take the drug at a later time based on their individual condition. Patients with both asthma and seasonal allergic rhinitis should take the drug once nightly. Adults aged 15 years and older with asthma and/or seasonal allergic rhinitis should take 10 mg once daily. Children aged 6 to 14 years with asthma and/or seasonal allergic rhinitis should take 5 mg once daily. Children aged 2 to 5 years with asthma and/or seasonal allergic rhinitis should take 4 mg once daily. Asthma control indicators are generally recommended as the evaluation of treatment efficacy. The efficacy of this product is apparent within one day of treatment. This product can be taken with or without food. Patients should be advised to continue taking the drug, regardless of whether their asthma is under control or exacerbated. No dosage adjustment is required for patients with renal insufficiency, mild to moderate hepatic impairment, or gender. This product can be added to a patient's existing treatment regimen. Reducing the dose of concomitant medications: For patients whose asthma is not effectively controlled with bronchodilators alone, this product can be added to the treatment regimen. Once a clinical response is observed (usually after the first dose), the bronchodilator dose can be reduced based on the patient's tolerance. For patients with asthma receiving inhaled corticosteroids, the dose of the corticosteroid can be appropriately reduced based on the patient's tolerance. This dose should be gradually reduced under medical supervision. Some patients can gradually reduce the dose until inhaled corticosteroids are completely discontinued. However, this product should not be used to abruptly replace inhaled corticosteroids or as directed by a physician.

[Adverse Reactions]
This product is generally well tolerated. Adverse reactions are mild and generally do not require discontinuation of treatment. The overall adverse reaction rate with this product is similar to that with placebo. For patients with asthma aged 1.5 years and older: This product has been evaluated in clinical studies in approximately 2,600 adult patients with asthma aged 15 years and older. In two similarly designed, placebo-controlled, 12-week clinical trials, abdominal pain and headache were drug-related adverse events that occurred in 1% of patients in the zetabine treatment group compared to the placebo group. However, the incidence of these adverse events was not significantly different between the two groups. In clinical studies, a total of 544 patients have been treated with zetabine for at least 6 months, 253 patients have been treated for 1 year, and 21 patients have been treated for 2 years. The incidence of adverse events did not change with the extension of the treatment duration of zetabine. 2. Patients aged 15 years and above with seasonal allergic rhinitis: Clinical studies have been conducted in 2,199 adult patients aged 15 years and above with seasonal allergic rhinitis to evaluate the safety of zetabine. The drug was well tolerated when taken once daily in the morning or evening, with an incidence of adverse reactions similar to that of placebo. In placebo-controlled clinical studies, the incidence of adverse events in the zetabine treatment group was less than 1%, and the incidence of somnolence was similar to that of the placebo group in all clinical studies. 3. Pediatric Asthma Patients Aged 6 and 14: This product has been evaluated in clinical studies in approximately 320 pediatric patients aged 6 to 14 years. Overall, the safety profile of this product in pediatric patients was similar to that of adults and comparable to placebo. In an 8-week placebo-controlled clinical trial, the only drug-related adverse event reported at a higher rate in the 1% of patients treated with this product compared to the placebo group was headache. However, the incidence of headache did not differ significantly between the two treatment groups. A total of 143 pediatric patients aged 6 to 14 years have been treated with this product for at least 3 months, and 44 patients have been treated for 6 months or longer. The adverse event profile did not change with longer treatment duration. 4. Pediatric Asthma Patients Aged 2 to 5: This product has been evaluated in approximately 573 pediatric patients aged 2 to 5 years. In a 12-week placebo-controlled clinical trial, the only drug-related adverse event reported at a higher rate in the 1% of patients treated with this product compared to the placebo group was thirst. However, the incidence of thirst did not differ significantly between the two treatment groups. A total of 426 pediatric patients aged 2 to 5 years have been treated with this product for at least 3 months, 230 patients have been treated for 6 months or longer, and 63 patients have been treated for 12 months or longer. The incidence of adverse events has not changed with the extension of the treatment time of this product. 5. Pediatric patients aged 2 to 14 years with seasonal allergic rhinitis: In a 2-week placebo-controlled clinical trial, the safety of this product has been evaluated in 280 patients aged 2 to 14 with seasonal allergic rhinitis. The safety profile of taking this product once a day in the evening was similar to that of the placebo group. In this study, the incidence of adverse reactions in the group treated with this product was less than 1%, and no drug-related adverse reactions were found, and the incidence was higher than that of the placebo group. 6. Postmarketing Experience: The following adverse reactions have been reported following postmarketing use of this product: hypersensitivity reactions (including anaphylaxis, angioedema, rash, pruritus, urticaria, and rarely, hepatic eosinophilic infiltration); abnormal dreams and hallucinations; somnolence, excitement, irritability, including aggressive behavior; restlessness; insomnia; paresthesia/tactile disturbances and, rarely, seizures; nausea, vomiting, dyspepsia, diarrhea; elevated ALT and AST; and, rarely, cholestatic hepatitis; arthralgia, including myalgia with muscle cramps; increased bleeding tendency, bruising, palpitations, and edema.

[Contraindications]
This product is contraindicated in patients with allergies to any of the ingredients.

[Precautions]
The efficacy of oral administration for the treatment of acute asthma attacks has not been established. Therefore, it should not be used for the treatment of acute asthma attacks. Although the dose of concomitant inhaled corticosteroids can be gradually reduced under the guidance of a physician, this product should not abruptly replace inhaled or oral corticosteroids. In patients receiving anti-asthma medications, including leukotriene receptor antagonists, reducing the dose of systemic corticosteroids may cause rare cases of one or more of the following: eosinophilia, vascular rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy (sometimes diagnosed as Churg-Strauss syndrome, a systemic eosinophilic vasculitis). Although a causal relationship between these conditions and leukotriene receptor antagonists has not been established, caution and appropriate clinical monitoring are recommended when reducing the dose of systemic corticosteroids in patients receiving this product.

[Use in Special Populations]
Precautions for Pediatric Patients:
1. Safety and efficacy studies have been conducted in children aged 6 months to 14 years. Safety and efficacy studies in children under 6 months of age have not been conducted. 2. Studies have shown that this product does not affect growth rate in children.

Precautions During Pregnancy and Lactation:
1. No data are available for use in pregnant women. Pregnant women should avoid taking this product unless clearly indicated.
2. Global post-marketing experience indicates rare reports of congenital limb defects in newborns following use of this product during pregnancy. The vast majority of these women also took other asthma medications during pregnancy. A causal relationship between this product and these events has not been established.
3. It is unknown whether this product is excreted in human breast milk. Because many drugs are excreted in human breast milk, this product should be used with caution in breastfeeding women.

Precautions for Elderly Patients:
Not applicable.

[Drug Interactions]
This product can be used in combination with other medications commonly used for the prevention and long-term treatment of asthma and the treatment of allergic rhinitis. In drug interaction studies, this product at the recommended dose did not produce clinically significant pharmacokinetic effects on the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin, and warfarin. The area under the plasma concentration-time curve (AUC) of montelukast decreases by approximately 40% in patients receiving concomitant phenobarbital. However, no dose adjustment is recommended. In vitro studies have shown that montelukast is an inhibitor of CYP2C8. However, data from a clinical drug interaction study between montelukast and rosiglitazone (a typical substrate primarily metabolized by CYP2C8) indicate that montelukast does not inhibit CYP2C8 in vivo. Therefore, montelukast is not expected to affect drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone, repaglinide). (See package insert for details.)

[Pharmacological Actions]
1. Pharmacology: Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory mediators released by various cell types, including mast cells and eosinophils. These important pro-asthma mediators bind to cysteinyl leukotrienes (CysLT) receptors. Type I cysteinyl leukotrienes (C... Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory mediators released by a variety of cells, including mast cells and eosinophils. These important pro-asthma mediators bind to cysteinyl leukotrienes (CysLT) receptors. Type I cysteinyl leukotrienes (CysLT1) receptors are distributed in the human airways (including airway smooth muscle cells and airway macrophages) and other pro-inflammatory cells (including eosinophils and certain bone marrow stem cells). CysLTs are associated with the pathophysiological processes of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include a series of airway reactions, such as bronchoconstriction, mucus secretion, Increased vascular permeability and eosinophil accumulation. In allergic rhinitis, the nasal mucosa releases CysLTs related to the symptoms of allergic rhinitis in both the immediate and delayed phase reactions after allergen exposure. Intranasal CysLTs stimulation increases nasal airway resistance and symptoms of nasal obstruction. This product is a potent oral preparation that can significantly improve asthma inflammation indicators. Biochemical and pharmacological bioassays have shown that montelukast has a high affinity and selectivity for the CysLT1 receptor (compared with other pharmacologically important airway receptors such as prostanoids, cholinergic and β-adrenergic receptors). Montelukast can effectively inhibit the binding of LTC4, LTD4LTE4 to the CysLT1 receptor. The physiological effects produced do not have any receptor agonist activity. Current studies suggest that montelukast does not antagonize the CysLT2 receptor. In a 12-month study conducted in children aged 6 to 14 years with mild persistent asthma (abbreviated as MOSAIC, a study of Montelukast in the treatment of childhood asthma), the efficacy of montelukast and inhaled fluticasone in controlling asthma were compared. Montelukast was non-inferior to fluticasone in increasing the percentage of emergency-free days for asthma (mean values ​​were 83.6% and 86.4%, respectively). Both montelukast and fluticasone are effective in controlling asthma: including increasing the forced expiratory volume in one second (FEV1, which increased by 0.27L and 0.30L compared to baseline, P= 0.232) and reduced the number of days using beta-agonists (reductions of 22.7% and 25.4% from baseline, respectively. P=0.003 between groups). Children 2-5 years old In a 12-month placebo-controlled study in children 2 to 5 years old with mild intermittent asthma and exacerbations induced by viral infection (PREVIA, Montelukast for Prevention of Viral-Induced Asthma Study), once-daily administration of montelukast 4 mg significantly reduced the frequency of asthma exacerbations compared with placebo. 2. Toxicology Acute toxicity In mice and rats, single oral doses of montelukast sodium up to 5000 mg/kg (15000 mg/m2 and 2 in mice and rats, respectively) resulted in a significant decrease in the frequency of asthma exacerbations. 9500mg/m2), no deaths occurred. This dose is the maximum dose tested (oral LD50... Acute toxicity: In mice and rats, no deaths occurred when a single oral dose of montelukast sodium was as high as 5000mg/kg (15000mg/m2 and 29500mg/m2 for mice and rats, respectively). This dose is the maximum dose tested (oral LD50>5000mg/kg), equivalent to 25,000 times the recommended daily dose for adults*. Long-term toxicity tests in monkeys and rats lasted up to 53 weeks, and in infant monkeys and mice up to 14 weeks. The results showed that montelukast sodium is well tolerated and the doses used have a wide safety range. . No effects on toxicological parameters were observed when montelukast sodium was administered to any of the experimental animals at doses of at least 125 times the recommended human dose*. No circumstances have been found in either adult or pediatric patients where therapeutic doses of montelukast sodium could not be used. Carcinogenicity Montelukast sodium was not found to be carcinogenic in studies in rats at oral doses of up to 200 mg/kg/day for 106 weeks and in mice at oral doses of up to 100 mg/kg/day for 92 weeks. These doses are equivalent to 1000 times and 500 times the recommended adult dose*. *Based on a 50 kg adult body weight Mutagenicity Montelukast sodium was not found to be genotoxic or mutagenic. In in vitro microbial mutation tests and V-79 mammalian cell culture experiments, the results were not consistent with the results of the previous studies. Montelukast sodium was negative in a dairy animal cell mutation assay, both in the presence and absence of metabolic activity. In an in vitro rat hepatocyte alkaline elution assay and a Chinese hamster ovary cell chromosome aberration assay, no genotoxic effects were observed in the presence and absence of a microsomal enzyme activity system. Similarly, no induction of chromosomal abnormalities in bone marrow cells was observed when montelukast sodium was administered orally to male or female mice at doses up to 1200 mg/kg (3600 mg/m2) (6000 times the recommended adult daily dose*). Reproductive toxicity In studies in which male rats were given oral doses of montelukast sodium up to 800 mg/kg/day and female rats were given oral doses up to 100 mg/kg/day, no effects on fertility or reproductive function were observed. These doses are 4000 and 500 times higher than the recommended adult dose, respectively.* In developmental toxicity studies, no treatment-related adverse effects were observed when montelukast sodium was administered to rats at doses up to 400 mg/kg/day and to rabbits at doses up to 100 mg/kg/day. Montelukast sodium has been reported in fetuses of rats and rabbits, and has been detected in the milk of lactating rats.

[Storage]
Store at room temperature (15-30°C), protected from moisture and light.

[Specifications]
5 mg tablets/box

[Packaging]
Aluminum-plastic packaging, 5 tablets/box.

[Expiration Date]
24 months

[Approval Number]
J20130054