Montelukast Sodium Chewable Tablets

Pharmacology Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent inflammatory mediators released by a variety of cells including mast cells and eosinophils. These important pro-asthmatic mediators bind to cysteinyl leukotriene (CysLT) receptors. Cysteinyl leukotriene type I (CysLT1) receptors are distributed throughout 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 pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include a range of airway responses such as bronchoconstriction, mucus secretion, increased vascular permeability, and eosinophil accumulation. In allergic rhinitis, CysLTs are released from the nasal mucosa in both the immediate and delayed phases following allergen exposure, which are associated with allergic rhinitis symptoms. Intranasal CysLT provocation increases nasal airway resistance and symptoms of nasal obstruction. This product is a potent oral preparation that can significantly improve asthma inflammatory indicators. Biochemical and pharmacological bioassays show that montelukast has a high affinity and selectivity for CysLT1 receptors (compared with other pharmacologically important airway receptors such as prostanoids, cholinergic and β-adrenergic receptors). Montelukast can effectively inhibit the physiological effects of LTC4, LTD4 and LTE4 binding to CysLT1 receptors without any receptor agonist activity. Current studies believe that montelukast does not antagonize CysLT2 receptors. Children aged 6-14 years old In a 12-month study conducted in children aged 6 to 14 years with mild persistent asthma (abbreviated as MOSAIC, Montelukast for the Treatment of Childhood Asthma Study), the efficacy of montelukast and inhaled fluticasone in controlling asthma were compared. Montelukast is not inferior to fluticasone in improving the percentage of emergency-free days for asthma (mean values are 83.6% and 86.4%, respectively). Both montelukast and fluticasone are effective in controlling asthma: including an increase in forced expiratory volume in one second (FEV1, 0.27L and 0.30L, respectively, from baseline; P = 0.232) and a reduction in the number of days on beta-agonists (22.7% and 25.4% from baseline, respectively; P = 0.003 between groups). Children 2-5 years of age In a 12-month placebo-controlled study in children aged 2 to 5 years 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. Toxicology Acute toxicity In mice and rats, no deaths occurred when single oral doses of montelukast sodium were up to 5000 mg/kg (15,000 mg/m2 and 29,500 mg/m2 in mice and rats, respectively). This dose is the maximum dose tested (oral LD50 5000 mg/kg), equivalent to 25,000 times the recommended daily dose for adults*. Long-term toxicity was tested for up to 53 weeks in monkeys and rats, and up to 14 weeks in infant monkeys and mice. The results showed that montelukast sodium was well tolerated and had a wide safety range for the doses used. No effects on toxicological parameters were found when all animals in the test were given montelukast sodium at least 125 times the recommended human dose*. No cases were found in adult and pediatric patients where montelukast sodium could not be used at therapeutic doses. Carcinogenicity Montelukast sodium was not found to be carcinogenic in studies of rats with oral doses of up to 200 mg/kg/day for 106 weeks and in mice with oral doses of up to 100 mg/kg/day for 92 weeks. These doses are equivalent to 1000 and 500 times the recommended adult dose*. Mutagenicity Montelukast sodium was not found to have genotoxic and mutagenic effects. Montelukast sodium showed negative reactions in the in vitro microbial mutation test and the V-79 mammalian cell mutation test, with or without metabolic activity. In the rat hepatocyte alkaline elution test and the Chinese hamster ovary cell chromosome aberration test in vitro, no genotoxic effects were observed, with or without the microsomal enzyme activity system. Similarly, no effects of inducing chromosomal abnormalities in bone marrow cells were found when montelukast sodium was orally administered to male or female mice at doses up to 1200 mg/kg (3600 mg/m2) (6000 times the recommended daily dose for adults*). *Reproductive toxicity based on an adult body weight of 50 kg In studies of oral administration of montelukast sodium up to 800 mg/kg/day in male rats and 100 mg/kg/day in female rats, no effects on fertility and reproductive capacity were found. These doses are 4000 times and 500 times higher than the recommended daily dose for adults*, 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. Fetal exposure to montelukast sodium did occur in rats and rabbits, and montelukast sodium was significantly detected in the milk of lactating rats.

The main ingredient of this product is montelukast, and its chemical name is [R-(E)]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl)vinyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid sodium. Molecular formula: C35H35ClNNaO3S Molecular weight: 608.18

This product is pink round tablets.

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

Once a day. Asthma patients should take it before bedtime. Allergic rhinitis patients can take the medicine at the time needed according to their own conditions. Patients with both asthma and seasonal allergic rhinitis should take the medicine once a night. Children aged 6 to 14 with asthma and/or seasonal allergic rhinitis should take one tablet (5 mg) once a day. Children aged 2 to 5 with asthma and/or allergic rhinitis should take one tablet (4 mg) once a day. It is generally recommended to evaluate the treatment effect based on asthma control indicators. The efficacy of this product will appear within one day of medication. This product can be taken with or without food. Patients should be advised to take it regardless of whether their asthma is under control or exacerbated. No dosage adjustment is required for patients with renal insufficiency, patients with mild to moderate liver damage, and patients of different genders. Relationship between this product and other asthma treatment drugs This product can be added to the patient's existing treatment plan. Reduce the dose of concomitant medications: Bronchodilators For asthma patients who cannot be effectively controlled by bronchodilators alone, this product can be added to the treatment plan. Once there is a clinical response to treatment (usually after the first dose of the drug), the dose of bronchodilators can be reduced according to the patient's tolerance. Inhaled corticosteroids For asthma patients receiving inhaled corticosteroids, after adding this product, the dose of corticosteroids can be appropriately reduced according to the patient's tolerance. The dose should be gradually reduced under the guidance of a physician. Some patients can gradually reduce the dose until inhaled corticosteroids are completely stopped. However, this product should not be used to suddenly replace inhaled corticosteroids or follow the doctor's advice.

This product is generally well tolerated, with mild adverse reactions, and usually does not require termination of treatment. The overall incidence of adverse reactions of this product is similar to that of placebo. Clinical studies have been conducted in approximately 475 pediatric patients aged 6 to 14 years to evaluate the use of this product. Overall, the safety of this product in pediatric patients is similar to that of adults and close to that of placebo. In a placebo-controlled 8-week clinical trial, the only adverse event related to the drug in the treatment group of this product, with an incidence of 1% and higher than that in the placebo group, was headache. However, there was no significant difference in the incidence of headache between the two groups. In a 56-week positive-controlled study (abbreviated as MOSAIC, a study of montelukast in the treatment of childhood asthma), the safety range was consistent with the safety range described previously. In clinical studies evaluating the effect on growth rate, the safety characteristics of this product for children are consistent with previous descriptions. A total of 263 pediatric patients aged 6 to 14 years have been treated with this product for at least 3 months, and 164 patients have been treated for 6 months or longer. The occurrence of adverse events has not changed with the extension of the treatment time of this product. The safety of montelukast has been evaluated in approximately 573 pediatric patients aged 2 to 5 years. In a placebo-controlled 12-week clinical trial, the only adverse event related to the drug, with an incidence of 1% and higher than the placebo group, was thirst. However, there was no significant difference in the incidence of thirst between the two groups. In a 12-month placebo-controlled clinical study (PREVIA, a study of montelukast in the treatment of childhood asthma), the safety range was consistent with the safety range described previously. A total of 426 pediatric patients aged 2 to 5 years have been treated with montelukast 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 occurrence of adverse events did not change with the extension of the treatment time of montelukast. Pediatric patients aged 2 to 14 years with seasonal allergic rhinitis The safety of montelukast has been evaluated in 280 patients aged 2 to 14 years with seasonal allergic rhinitis in a 2-week placebo-controlled clinical trial. The safety profile of montelukast taken once a day in the evening was similar to that of the placebo group. In this study, the incidence of adverse reactions in the treatment group of this product was less than 1%, and no adverse reactions related to the drug were found, with an incidence higher than that in the placebo group. Pooled analysis of clinical practice A pooled analysis of 41 placebo-controlled clinical studies (35 studies on patients aged 15 years and above and 6 studies on pediatric patients aged 6 to 14 years) was conducted using a validated suicidal behavior assessment method. Among 9,929 patients taking this product and 7,780 patients taking placebo, one patient with suicidal thoughts took this product. No completed suicide, suicide attempt, or preparatory actions for suicidal behavior occurred in any group. An independent pooled analysis of 46 placebo-controlled clinical studies (35 studies on patients aged 15 years and above and 11 studies on pediatric patients aged 3 months to 14 years) was conducted to assess behavioral-related adverse events. Behavior-related adverse events occurred in 2.73% of the 11,673 patients taking tadalafil and 2.27% of the 8,827 patients taking placebo, with an odds ratio of 1.12 (95% CI [0.93:1.36]). The clinical trials included in these pooled analyses were not specifically designed to examine suicide rates or behavior-related adverse events. Postmarketing Experience The following adverse reactions have been reported with postmarketing use of tadalafil: Infections and infections: Upper respiratory tract infections. Blood and lymphatic system disorders: Increased bleeding tendency. Immune system disorders: Hypersensitivity reactions including allergic reactions, rare eosinophilic infiltration of the liver. Psychiatric disorders: Excitement including aggressive behavior or hostility, anxiety, depression, disorientation, abnormal dreams, hallucinations, insomnia, irritability, restlessness, sleepwalking, suicidal thoughts and behaviors (suicidal), tremor. Nervous system disorders: Dizziness, somnolence, paresthesia/hypoptosis, and rare seizures. Cardiac disorders: Palpitations. Respiratory, thoracic and mediastinal disorders, epistaxis. Gastrointestinal disorders: ALT and AST increased, very rare hepatitis (including cholestatic, hepatocellular and mixed liver damage). Skin and subcutaneous tissue disorders: angioedema, contusions, erythema nodosum, pruritus, rash, urticaria. Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps. Other disorders and administration site conditions: asthenia/fatigue, edema, fever.

Do not use if you are allergic to any ingredient in this product.

Precautions for children: Safety and efficacy studies have been conducted in children aged 6 months to 14 years. The safety and efficacy of pediatric patients under 6 months have not been studied. Studies have shown that this product does not affect the growth rate of children. Precautions for pregnancy and lactation: There is no research data on pregnant women. Pregnant women should avoid taking this product unless it is clearly necessary to take the medicine. Global post-marketing experience shows that there are rare reports of congenital limb defects in newborns after using this product during pregnancy. The vast majority of these women also used other asthma treatment drugs during pregnancy. The causal relationship between the use of this product and these events has not been established. It is not clear whether this product can be secreted in breast milk. Since many drugs can be secreted in breast milk, breastfeeding women should use this product with caution. Precautions for the elderly: Not applicable.

This product can be used in combination with other drugs routinely used for the prevention and long-term treatment of asthma and the treatment of allergic rhinitis. In drug interaction studies, the recommended dose of this product 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. In patients taking phenobarbital concomitantly, the area under the plasma concentration-time curve (AUC) of montelukast was reduced by approximately 40%. However, it is not recommended to adjust the dosage of this product. In vitro tests have shown that montelukast is an inhibitor of CYP28. However, data from a clinical study on the drug interaction between montelukast and rosiglitazone (a typical detection substrate that is mainly metabolized by CYP28) showed that montelukast sodium had no inhibitory effect on CYP28 in vivo. Therefore, it is believed that montelukast sodium will not affect drugs metabolized by this enzyme (such as paclitaxel, rosiglitazone, repaglinide). In vitro studies have shown that montelukast is a substrate for CYP2C8, 2C9, and 3A4. A clinical drug interaction study involving montelukast and gemfibrozil (an inhibitor of CYP2C8 and 2C9) demonstrated that gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. Itraconazole, a strong inhibitor of CYP3A4, did not further increase the systemic exposure of montelukast when co-administered with gemfibrozil and montelukast. In clinical safety studies, doses greater than the 10 mg approved in adults (e.g., 200 mg/day for 22 consecutive weeks in adult patients and up to 900 mg/day for approximately 1 week in patients) were used, and no clinically significant adverse events were observed. Based on such data, the effect of gemfibrozil on the systemic exposure of montelukast is considered to be clinically insignificant. Therefore, no dose adjustment of montelukast is required when co-administered with gemfibrozil. Based on in vitro data, clinically significant drug interactions are not expected to occur between montelukast and other known CYP2C8 inhibitors (e.g., trimethoprim). In addition, coadministration of montelukast alone with itraconazole does not significantly increase the systemic exposure of montelukast.

Store at room temperature, in a dark place, sealed and dry.

5mg*7 tablets*2 plates

24 months.

Qilu Pharmaceutical (Hainan) Co., Ltd.

• Founded in:

  2005-10-18

• Address:

  No. 273-A, Nanhai Avenue, National High-tech Zone, Haikou City

• Tax NO.:

  91460000780701210W

• Registered Funds:

  40 million yuan

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