QILU RUNPEI Montelukast Sodium Chewable Tablets For Children's Allergies 5mg*14

[Drug Name]
Generic Name: Montelukast Sodium Chewable Tablets
Trade Name: Runpei
English Name: Montelukast Sodium Chewable Tablets
Chinese Pinyin: Menglusitena Jujuepian

[Ingredients]
The main ingredient of this product is montelukast, whose 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

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

[Indications]
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. 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).

[Dosage and Administration]
Once daily. Patients with asthma should take the drug at bedtime. Patients with allergic rhinitis may take the drug at a later time, depending on their condition. Patients with both asthma and seasonal allergic rhinitis should take the drug once nightly. Children aged 6 to 14 years with asthma and/or seasonal allergic rhinitis: Take one tablet (5 mg) once daily. Children aged 2 to 5 years with asthma and/or allergic rhinitis: Take one tablet (4 mg) once daily. General Recommendations: Asthma control measures should be used to evaluate treatment effectiveness. The effectiveness of this product is evident within one day of treatment. This product can be taken with or without food. Patients should be advised to continue taking this product 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. Relationship with other asthma medications: This product can be added to a patient's existing treatment regimen. Reduce the dose of concomitant medications: Bronchodilators: For patients with asthma 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. Inhaled corticosteroids: For patients with asthma receiving inhaled corticosteroids, the dose of the corticosteroid can be appropriately reduced based on the patient's tolerance. This reduction should be done gradually under the guidance of a physician. 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 on a physician's advice.

[Adverse Reactions]
This product is generally well tolerated, with mild adverse reactions that generally do not require discontinuation of treatment. The overall incidence of adverse reactions with this product is similar to that with placebo. Clinical studies have evaluated the use of this product in approximately 475 pediatric patients aged 6 to 14 years. Overall, the safety profile of this product in pediatric patients is similar to that in adults and close to that of placebo. In an 8-week, placebo-controlled clinical trial, the only adverse event reported as drug-related, occurring at a rate >1% and at a higher rate than placebo in the montelukast-treated group, was headache. However, the incidence of headache did not differ significantly between the two groups. In a 56-week, active-controlled study (MOSAIC, the Montelukast in Childhood Asthma Study), the safety profile was consistent with that previously described. In clinical studies evaluating the effects on growth velocity, the safety profile of montelukast in children was consistent with that previously described. A total of 263 pediatric patients aged 6 to 14 years have been treated with montelukast for at least 3 months, and 164 patients for 6 months or longer. The adverse event profile did not change with longer treatment duration. The safety of montelukast has been evaluated in approximately 573 pediatric patients aged 2 to 5 years with asthma. In a 12-week, placebo-controlled clinical trial, the only adverse event reported as drug-related, occurring at a rate >1% and at a higher rate than placebo in the montelukast-treated group, was thirst. However, the incidence of thirst did not differ significantly between the two groups. In a 12-month, placebo-controlled clinical study (PREVIA, the Montelukast for Pediatric Asthma Study), the safety profile was consistent with previously described safety profiles. A total of 426 pediatric patients aged 2 to 5 years were treated with this product for at least 3 months, 230 patients were treated for 6 months or longer, and 63 patients were treated for 12 months or longer. The incidence of adverse events did not change with longer treatment duration. In a 2-week, placebo-controlled clinical trial, the safety profile of this product was evaluated in 280 patients aged 2 to 14 years with seasonal allergic rhinitis. The safety profile of this product, taken once daily in the evening, was similar to that of the placebo group. In this study, the incidence of adverse reactions in the montelukast-treated group was less than 1%, and no drug-related adverse reactions were found to be higher than those in the placebo group. Pooled Analysis of Clinical Practice: A pooled analysis of 41 placebo-controlled clinical studies (35 studies in patients 15 years of age and older and 6 studies in pediatric patients 6 to 14 years of age) was conducted using validated methods to assess suicidal behavior. Among 9929 patients taking dapagliflozin and 7780 patients taking placebo, one patient with suicidal ideation took dapagliflozin. Completed suicides, suicide attempts, or preparatory actions toward suicidal behavior were not reported in either group. A separate pooled analysis of 46 placebo-controlled clinical studies (35 studies in patients 15 years of age and older and 11 studies in pediatric patients 3 months to 14 years of age) assessed behavior-related adverse events. Among 11,673 patients taking dapagliflozin and 8,827 patients taking placebo, the incidence of behavior-related adverse events was 2.73% and 2.27%, respectively, for an odds ratio of 1.12 (95% CI 0.93:1.36). The clinical trials included in these pooled analyses were not designed to examine suicidality or behavior-related adverse events. Postmarketing Experience The following adverse reactions have been reported following postmarketing use of this product: Infections and infections: Upper respiratory tract infection. 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 (suicide), tremor. Nervous system disorders: Dizziness, somnolence, paresthesia/hypoesthesia, and rare epileptic seizures. Cardiac disorders: Palpitations. Respiratory, thoracic, and mediastinal system disorders, epistaxis. Gastrointestinal disorders: Elevated ALT and AST, 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.

[Contraindications]
This product should not be used if you are allergic to any of the ingredients in it.

[Precautions]
The efficacy of this oral medication for the treatment of acute asthma exacerbations has not been established. Therefore, it should not be used to treat acute asthma exacerbations. Patients should be advised to have appropriate rescue medications available. Although the dose of concomitant inhaled corticosteroids can be gradually reduced under the guidance of a physician, this medication should not be used abruptly to replace inhaled or oral corticosteroids. Rarely, patients receiving anti-asthma medications, including leukotriene receptor antagonists, have experienced 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). These events have sometimes been associated with reduction or discontinuation of oral corticosteroid therapy. Although a causal relationship to leukotriene receptor antagonists has not been established, caution and appropriate clinical monitoring are recommended for patients taking this medication. Patients with phenylketonuria should be informed that the 4 mg and 5 mg chewable tablets contain 0.674 and 0.842 mg of phenylalanine (a component of aspartame), respectively. Montelukast may have little or no effect on the ability to drive or operate machinery. However, isolated cases of drowsiness and dizziness have been reported. Neuropsychiatric events have been reported in adults, adolescents, and children taking the original montelukast sodium chewable tablets. Postmarketing reports of these events with the original montelukast sodium chewable tablets include excitement, aggressive behavior or hostility, anxiety, depression, disorientation, attention deficit disorder, abnormal dreams, hallucinations, insomnia, irritability, memory impairment, restlessness, sleepwalking, suicidal thoughts and behaviors (including suicide), convulsions, and tremors. Clinical details in some postmarketing reports of the original montelukast sodium chewable tablets appear consistent with drug-induced effects. Psychiatric and neurological events have been reported in patients taking the original montelukast sodium chewable tablets (see Adverse Reactions). Because other factors may contribute to these events, a relationship to the original montelukast sodium chewable tablets cannot be confirmed. Physicians should discuss these adverse events with patients and/or caregivers. Patients and/or caregivers should be advised to notify their physicians if these events occur. Patients with known aspirin sensitivity should continue to avoid aspirin or nonsteroidal anti-inflammatory drugs while taking this product.

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

Pregnancy and Lactation Precautions:
No data are available from studies in pregnant women. Pregnant women should avoid this product unless specifically indicated. Global post-marketing experience has shown rare reports of congenital limb defects in newborns after using 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. 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.

Elderly Precautions:
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 for the treatment of allergic rhinitis. In drug interaction studies, the recommended dose of montelukast 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 was reduced by approximately 40% in patients taking phenobarbital concomitantly. However, no dose adjustment of montelukast is recommended. In vitro studies have shown that montelukast is an inhibitor of CYP28. However, data from a clinical drug interaction study of montelukast and rosiglitazone (a typical probe substrate primarily metabolized by CYP28) showed that montelukast sodium did not inhibit CYP28 in vivo. Therefore, montelukast sodium is not expected to affect drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone, repaglinide). In vitro studies have shown that montelukast is a substrate of CYP 2C8, 2C9, and 3A4. A clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of CYP2C8 and 2C9) demonstrated that gemfibrozil increased montelukast systemic exposure by 4.4-fold. Concomitant administration of itraconazole, a strong CYP 3A4 inhibitor, with gemfibrozil and montelukast did not further increase montelukast systemic exposure. In clinical safety studies, no clinically significant adverse events were observed at doses greater than the approved 10 mg dose in adults (e.g., 200 mg/day for 22 consecutive weeks and up to 900 mg/day for approximately one week). Based on these data, the effect of gemfibrozil on montelukast systemic exposure was not considered clinically relevant. Therefore, no dose adjustment of montelukast is required with concomitant administration of gemfibrozil. Based on in vitro data, no clinically significant drug-drug interactions are expected between montelukast and other known CYP2C8 inhibitors, such as trimethoprim. Furthermore, coadministration of montelukast with itraconazole alone did not significantly increase the systemic exposure of montelukast.

[Pharmacological Actions]
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. Type I cysteinyl leukotriene (CysLT1) receptors are located 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 implicated in 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, nasal mucosa releases CysLTs, which are associated with allergic rhinitis symptoms, during both the immediate and delayed phases following allergen exposure. Intranasal CysLT provocation increases nasal airway resistance and symptoms of nasal obstruction. This product is a potent oral formulation that significantly improves inflammatory markers in asthma. Biochemical and pharmacological bioassays have demonstrated that montelukast has a high affinity and selectivity for the CysLT1 receptor (compared to other pharmacologically important airway receptors such as prostanoids, cholinergic, and β-adrenergic receptors). Montelukast effectively inhibits the physiological effects of LTC4, LTD4, and LTE4 binding to the CysLT1 receptor without any receptor agonist activity. Current studies suggest that montelukast does not antagonize the CysLT2 receptor. In a 12-month study (MOSAIC, Montelukast in Children with Asthma) conducted in children aged 6 to 14 years with mild persistent asthma, the Montelukast Study compared the efficacy of inhaled fluticasone for asthma control. Montelukast was noninferior to fluticasone in improving the percentage of emergency-free days (mean 83.6% vs. 86.4%, respectively). Both montelukast and fluticasone were effective in controlling asthma, including increases in forced expiratory volume in one second (FEV1) by 0.27 L and 0.30 L, respectively, compared with baseline (P=0.232) and reductions in beta-agonist use days (22.7% and 25.4%, respectively, compared with baseline; P=0.003 for both groups). Children 2-5 Years Old: In a 12-month, placebo-controlled study (PREVIA, Montelukast for Prevention of Viral-Induced Asthma Study) in children 2 to 5 years of age with mild, intermittent asthma and viral exacerbations, montelukast 4 mg once daily significantly reduced the frequency of asthma exacerbations compared with placebo. Toxicology: Acute Toxicity: No mortality occurred in mice and rats following single oral administration of montelukast sodium at doses up to 5000 mg/kg (15,000 mg/m² in mice and 29,500 mg/m² in rats). This dose was the maximum dose tested (oral LD50 > 5000 mg/kg) and is equivalent to 25,000 times the recommended daily dose in adults*. Long-Term Toxicity: Studies lasted up to 53 weeks in monkeys and rats and up to 14 weeks in infant monkeys and mice. Montelukast sodium was well tolerated and had a wide safety margin at the doses used. No effects on toxicological parameters were observed when montelukast sodium was administered to all animals studied at doses at least 125 times the recommended human dose.* No instances of montelukast sodium withholding at therapeutic doses were observed in either adult or pediatric patients. Carcinogenicity: Montelukast sodium was not found to be carcinogenic in rats at oral doses up to 200 mg/kg/day for 106 weeks and in mice at oral doses up to 100 mg/kg/day for 92 weeks. These doses correspond to 1000 and 500 times the recommended adult dose.* Mutagenicity: Montelukast sodium was not found to be genotoxic or mutagenic. Montelukast sodium was negative in the in vitro microbial mutation assay and the V-79 mammalian cell mutation assay, both with and without metabolic activity. No genotoxic effects were observed in the in vitro rat hepatocyte alkaline elution assay and the Chinese hamster ovary cell chromosome aberration assay, both with and without microsomal enzyme activity systems. Similarly, oral administration of montelukast sodium to male or female mice at doses up to 1200 mg/kg (3600 mg/m²) (6000 times the recommended adult daily dose*) did not induce chromosomal abnormalities in bone marrow cells. *Based on a 50 kg adult body weight. 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 capacity were observed. These doses are 4000 times and 500 times higher than the recommended adult dose, respectively*. In developmental toxicity studies, no treatment-related adverse effects were observed at doses up to 400 mg/kg/day in rats and 100 mg/kg/day in rabbits. Montelukast sodium has been reported in rats and rabbits to be exposed to fetal fertility, and it has been detected in the milk of lactating rats.

[Storage]
Store in a dry, airtight container at room temperature, protected from light.

[Specification]
5mg x 14 tablets

[Packaging]
Aluminum-plastic packaging with a polyester/aluminum/polyethylene composite film bag (containing a desiccant), 14 tablets/box.

[Expiration Period]
24 months.

[Approval Number]
National Medicine Standard H20203124

[Manufacturer]
Company Name: Qilu Pharmaceutical (Hainan) Co., Ltd.