Singulair, pills 10mg, 28pcs

Composition

1 tablet contains:

Main substance:

Montelukast sodium 10.4 mg (which corresponds to the content of montelukast 10 mg).

Auxiliary substances:

Giprolose (hydroxypropylcellulose) – 4 mg;

Microcrystalline cellulose-89.3 mg;

Lactose monohydrate – 89.3 mg;

Croscarmellose sodium – 6 mg;

Magnesium stearate – 1 mg.

Shell composition:

Giprolose (hydroxypropylcellulose) – 1.73 mg;

Hypromellose (methylhydroxypropylcellulose) – 1.73 mg;

Titanium dioxide (E171) – 1.5 mg;

Iron oxide red (E172) – 0.004 mg;

Iron oxide yellow (E172) – 0.036 mg;

Carnauba wax – 0.006 mg.

Active ingredients

Montelukast.

Clinical pharmacology

Leukotriene receptor antagonist. A drug for the treatment of bronchial asthma and allergic rhinitis. Pharmaco-therapeutic group: Leukotriene receptor antagonistpharmacological actionleukotriene receptor antagonist. Cysteinyl leukotrienes LTC4, LTD4, LTE4 are strong mediators of inflammation – eicosanoids, which are secreted by various cells, including mast cells and eosinophils.

These important pro-asthmatic mediators bind to cysteinyl leukotriene receptors. Cysteinyl leukotriene type I receptors (CysLT1 receptors) are present in the human respiratory tract (including bronchial smooth muscle cells, macrophages) and other pro-inflammatory cells (including eosinophils and some myeloid stem cells).

Cysteinyl leukotrienes correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, increased mucus secretion, increased vascular permeability, and increased eosinophil count. In allergic rhinitis, after exposure to an allergen, cysteinyl leukotrienes are released from pro-inflammatory cells of the nasal mucosa during the early and late phases of an allergic reaction, which is manifested by symptoms of allergic rhinitis. An intranasal test with cysteinyl leukotrienes showed increased resistance of the nasal airways and a symptom of nasal obstruction.

Montelukast is a highly active drug when taken orally, which significantly improves the indicators of inflammation in bronchial asthma. According to biochemical and pharmacological analysis, montelukast binds to CysLT1 receptors with high affinity and selectivity, without interacting with other pharmacologically important receptors in the respiratory tract (such as prostaglandin receptors, choline or beta-adrenergic receptors). Montelukast inhibits the physiological action of cysteinyl leukotrienes LTC4, LTD4, LTE4 by binding to CysLT1 receptors, without exerting a stimulating effect on these receptors.

Montelukast inhibits CysLT receptors in the respiratory tract, which is confirmed by its ability to block the development of bronchospasm in response to LTD4 inhalation in patients with bronchial asthma. A dose of 5 mg is sufficient to relieve LTD4-induced bronchospasm.

Montelukast causes bronchodilation within 2 hours after oral use and may supplement the bronchodilation caused by beta-2-adrenomimetics.

The use of montelukast in doses greater than 10 mg/day once does not increase the effectiveness of the drug. Pharmacokinetics

Suction. After oral use, montelukast is rapidly and almost completely absorbed from the gastrointestinal tract. In adults, when taking coated tablets on an empty stomach at a dose of 10 mg, Cmax in blood plasma is reached after 3 hours. The average oral bioavailability is 64%. Food intake does not affect the Cmax in blood plasma and bioavailability of the drug. Distribution. The binding of montelukast to plasma proteins is more than 99%. The average VD is 8-11 liters. Studies with radioactively labeled montelukast conducted on rats indicate minimal penetration through the BBB. In addition, labeled drug concentrations were minimal in all other tissues 24 hours after use. When taking montelukast at a dose of 10 mg 1 time / day, moderate (about 14%) accumulation of the Active ingredient in plasma is observed. Metabolism. Montelukast is actively metabolized in the liver. When used in therapeutic doses, the concentration of montelukast metabolites in plasma at steady state in adults and children is not determined. In vitro studies using human liver microsomes have shown that cytochrome P 450 isoenzymes participate in the metabolism of montelukast: 3 A 4,2 C 8 and 2 C 9. According to the results of studies conducted in vitro in human liver microsomes, montelukast in therapeutic concentrations in blood plasma does not inhibit cytochrome P 450 isoenzymes: 3 A 4,2 C 9,1 A 2,2 A 6,2 C 19 and 2D6. Output. Plasma clearance of montelukast in healthy adults averages 45 ml/min. After ingestion of radioactively labeled montelukast,86% of its amount is excreted in the faeces within 5 days and less than 0.2% in the urine, which confirms that montelukast and its metabolites are excreted almost exclusively in the bile. T1 / 2 of montelukast in young healthy adults is from 2.7 to 5.5 h. The pharmacokinetics of montelukast remain almost linear when taking oral doses of more than 50 mg. When taking montelukast in the morning and evening hours, there are no differences in pharmacokinetics. Pharmacokinetics in special clinical cases. The pharmacokinetics of montelukast in women and men are similar. There were no differences in clinically significant pharmacokinetic effects in patients depending on race. When taking oral coated tablets at a dose of 10 mg 1 time/day, the pharmacokinetic profile and bioavailability are similar in elderly and young patients. In patients with mild to moderate hepatic insufficiency and clinical manifestations of cirrhosis of the liver, a slowdown in the metabolism of montelukast was observed, accompanied by an increase in AUC by approximately 41% after a single dose of 10 mg of the drug. The elimination of montelukast in these patients is slightly increased compared to healthy subjects (T1 / 2 on average is 7.4 hours). No dose adjustment of montelukast is required for patients with mild to moderate hepatic insufficiency. There are no data on the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale). Since montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast in patients with renal insufficiency have not been evaluated. No dose adjustment is required in this category of patients.

Indications

Prevention and long-term treatment of bronchial asthma in adults and children aged 6 years and older, including: :

• Prevention of day and night symptoms of the disease;
• Treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid;
• Prevention of exercise-induced bronchospasm.

Relief of daily and nocturnal symptoms of seasonal and / or year-round allergic rhinitis (in adults and children aged 6 years and older).

Use during pregnancy and lactation

There have been no clinical studies of the drug Singulair with the participation of pregnant women. Singulair should only be used during pregnancy and lactation when the expected benefit to the mother exceeds the potential risk to the fetus or child. In the course of post-marketing use of the drug Singulair, the development of congenital limb defects in newborns whose mothers took Singulair during pregnancy was reported. Most of these women also took other medications to treat asthma during pregnancy. A causal relationship between taking the drug Singulair and the development of congenital limb defects has not been established. It is not known whether montelukast is excreted in breast milk. Since many medications are excreted in breast milk, this should be taken into account when prescribing Singulair to breast-feeding mothers.

Recommendations for use

The drug is available on prescription.

Contraindications

• Children under 6 years of age;
• Phenylketonuria;
• Hypersensitivity to the components of the drug.

Side effects

In general, the drug Singulair is well tolerated by patients. Side effects are usually mild and usually do not require discontinuation of the drug. The overall incidence of side effects with Singulair is comparable to that of placebo.

Children aged 2 to 5 years with bronchial asthma

573 patients aged 2 to 5 years participated in clinical trials of the drug Singulair. In a 12-week placebo-controlled clinical trial, the only adverse event (AES) assessed as drug-related occurred in >1% of patients treated with Singulair, and more often than in the placebo group, was thirst. The differences in the frequency of this AE between the two treatment groups were statistically insignificant. A total of 426 patients aged 2 to 5 years were treated with Singulair for at least 3 months,230 for 6 months or longer, and 63 patients for 12 months or longer. With longer treatment, the AES profile did not change.

Children aged 2 to 14 years with seasonal allergic rhinitis

280 patients aged 2 to 14 years participated in a 2-week placebo-controlled clinical trial using the drug Singulair for the treatment of seasonal allergic rhinitis. Patients took Singulair 1 time / day in the evening and were generally well tolerated. The safety profile of the drug in children was similar to that of placebo.In this clinical study, no AES were reported that would be considered drug-related, would occur in ≥1% of patients taking Singulair, and more often than in the group of patients taking placebo.

Children aged 6 to 14 years with bronchial asthma

The safety profile of the drug in children was generally similar to that of adults and comparable to that of placebo. In an 8-week placebo-controlled clinical trial, the only AES assessed as drug-related, occurring in >1% of patients treated with Singulair, and more often than in the placebo group, was headache. The difference in frequency between the two treatment groups was statistically insignificant. In studies evaluating the growth rate, the safety profile in patients of this age group corresponded to the previously described safety profile of Singulair. With longer treatment (more than 6 months), the AES profile did not change.

Adults and children aged 15 years and older with bronchial asthma

In two 12-week placebo-controlled clinical trials with a similar design, the only side effects assessed as drug-related, observed in ≥1% of patients taking Singulair, and more often than in the placebo group, were abdominal pain and headache. The differences in the frequency of these side effects between the two treatment groups were statistically insignificant. With longer treatment (over 2 years), the side effect profile did not change.

Adults and children aged 15 years and older with seasonal allergic rhinitis

Patients took Singulair 1 time / day in the morning or evening, and the drug was generally well tolerated. The safety profile of the drug was similar to that of placebo. In placebo-controlled clinical trials, no AES were reported that would be considered drug-related, would occur in ≥1% of patients treated with Singulair, and more often than in the group of patients taking placebo. In the 4-week placebo-controlled clinical trial, the safety profile of the drug was similar to that in the 2-week studies. The incidence of drowsiness when taking the drug in all studies was the same as when taking placebo.

Adults and children aged 15 years and older with year-round allergic rhinitis

Patients took Singulair 1 time / day in the evening, and the drug was generally well tolerated. The safety profile of the drug was similar to that observed in the treatment of patients with seasonal allergic rhinitis and when taking placebo. In these clinical trials, no AES were reported that would be considered drug-related, would occur in ≥1% of patients treated with Singulair®, and more often than in the group of patients receiving placebo. The incidence of drowsiness with the drug was the same as with placebo.

Generalized analysis of the results of clinical trials

A summary analysis of 41 placebo-controlled clinical trials (35 studies involving patients aged 15 years and older,6 studies involving patients aged 6 to 14 years) was performed using approved methods for assessing suicidality. Among 9929 patients treated with Singulair and 7780 patients treated with placebo in these studies,1 patient was identified with a suicidal mood in the group of patients treated with Singulair. No suicides, suicidal attempts, or other preparatory actions indicative of suicidal behavior were committed in any of the treatment groups. A separate pooled analysis of 46 placebo-controlled clinical trials (35 studies involving patients aged 15 years and older; 11 studies involving patients aged 3 months to 14 years)was performed. to assess adverse behavioral effects. Among the 11,673 patients treated with Singulaire and 8,827 patients treated with placebo in these studies, the percentage of patients with at least one adverse behavioral effect was 2.73% among patients treated with Singulaire and 2.27% among patients treated with placebo; the odds ratio was 1.12 (95% confidence interval [0.93; 1.36]). AES registered during post-marketing use of the drug

• Infectious and parasitic diseases: upper respiratory tract infections.
• From the side of the blood coagulation system: increased tendency to bleeding.
• Immune system disorders: hypersensitivity reactions, including anaphylaxis; very rare (
• From the side of the psyche: agitation (including aggressive behavior or hostility), anxiety, depression, disorientation, attention disorders, pathological dreams, hallucinations, insomnia, memory disorders, psychomotor activity (including irritability, anxiety and tremor), somnambulism, suicidal thoughts and behavior (suicidality).
• Nervous system disorders: dizziness, drowsiness, paresthesia/hypesthesia; very rare (
• From the cardiovascular system: rapid heartbeat.
• Respiratory system disorders: nosebleeds, pulmonary eosinophilia.
• From the digestive system: diarrhea, dyspepsia, nausea, vomiting, pancreatitis.
• Liver and biliary tract disorders: increased ALT and ACT activity in the blood; very rare (
• Skin and subcutaneous tissue disorders: tendency to form hematomas, erythema nodosum, erythema multiforme, pruritus, rash.
• Allergic reactions: angioedema, urticaria.
• Musculoskeletal disorders: arthralgia, myalgia, including muscle cramps.
• From the urinary system: enuresis in children.
• General reactions: asthenia (weakness)/fatigue, swelling, pyrexia.

Interaction

Singulair can be prescribed together with other medications traditionally used for the prevention and long-term treatment of bronchial asthma and/or the treatment of allergic rhinitis. Montelukast at the recommended therapeutic dose did not have a clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.

With simultaneous use of phenobarbital, the AUC value of montelukast decreases by about 40%, but this does not require changes in the dosage regimen of Singulair.

In vitro studies have shown that montelukast inhibits the CYP2C8 isoenzyme. However, an in vivo drug interaction study of montelukast and rosiglitazone (metabolized with the participation of the CYP2C8 isoenzyme) did not confirm the inhibition of the CYP2C8 isoenzyme by montelukast. Therefore, in clinical practice, montelukast is not expected to affect the CYP2C8-mediated metabolism of a number of drugs, including paclitaxel, rosiglitazone, and repaglinide.

In vitro studies have shown that montelukast is a substrate of CYP2C8,2C9 and 3A4. Data from a clinical drug interaction study with montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9) demonstrate that gemfibrozil increases the effect of systemic exposure to montelukast by 4.4 times. Co-use of itraconazole, a potent CYP3A4 inhibitor, together with gemfibrozil and montelukast did not lead to an additional increase in the effect of systemic exposure to montelukast. The effect of gemfibrozil on the systemic effects of montelukast cannot be considered clinically significant based on safety data when used at doses exceeding the approved dose of 10 mg for adult patients (for example,200 mg/day for adult patients for 22 weeks and up to 900 mg/day for patients taking the drug for about one week, no clinically significant adverse effects were observed).

Thus, when co-administered with gemfibrozil, no dose adjustment of montelukast is required. According to the results of in vitro studies, no clinically significant drug interaction with other known CYP2C8 inhibitors (for example, trimethoprim) is expected. In addition, co-use of montelukast with itraconazole alone did not significantly increase the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators

Singulair is a reasonable adjunct to monotherapy with bronchodilators, if the latter do not provide adequate control of bronchial asthma. After achieving the therapeutic effect of treatment with Singulair, you can start gradually reducing the dose of bronchodilators.

Combined treatment with inhaled corticosteroids

Treatment with Singulair provides an additional therapeutic effect in patients using inhaled corticosteroids. When the condition is stabilized, you can start gradually reducing the dose of corticosteroids under the supervision of a doctor. In some cases, complete withdrawal of inhaled corticosteroids is acceptable, but abrupt replacement of inhaled corticosteroids with Singulair is not recommended.

How to take it, course of use and dosage

The drug is taken orally 1 time/day, regardless of food intake. For the treatment of bronchial asthma, Singulair should be taken in the evening. In the treatment of allergic rhinitis, the drug can be taken at any time of the day. In case of combined pathology (bronchial asthma and allergic rhinitis), the drug should be taken in the evening. Adults and adolescents aged 15 years and older are prescribed the drug at a dose of 10 mg (1 tablet, coated)/day. General recommendationsthe therapeutic effect of the drug Singulair on indicators reflecting the course of bronchial asthma develops during the first day.The patient should continue to take Singulair both during the period of achieving control of symptoms of bronchial asthma, and during periods of exacerbation of bronchial asthma. For elderly patients, patients with renal insufficiency, as well as patients with mild or moderate hepatic impairment, as well as depending on gender, special dose adjustment is not required. use of the drug Singulair simultaneously with other types of treatment of bronchial asthmapreparation Singulair can be added to the patient’s treatment with bronchodilators and inhaled corticosteroids.

Overdose

Symptoms of overdose were not detected during clinical studies of long-term (22 weeks) treatment with Singulair in adult patients with bronchial asthma at doses up to 200 mg/day, or during short (about 1 week) clinical studies when taking the drug at doses up to 900 mg / day. There were cases of acute overdose of the drug Singulair (taking at least 1000 mg/day) in the post-marketing period and during clinical studies in adults and children. Clinical and laboratory data showed comparability of safety profiles of Singulair in children, adults, and elderly patients. The most common symptoms were thirst, drowsiness, vomiting, psychomotor agitation, headache, and abdominal pain. These side effects are consistent with the safety profile of Singulair. Treatment: performing symptomatic therapy. There is no specific information on the treatment of Singulair overdose. There are no data on the efficacy of peritoneal dialysis or montelukast hemodialysis.

Special instructions

The effectiveness of the drug Singulair for oral use in the treatment of acute attacks of bronchial asthma has not been established. Therefore, Singulair tablets are not recommended for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always carry emergency medications for managing asthma attacks (short-acting inhaled beta-2 agonists). Do not stop taking the drug Singulair during the period of exacerbation of asthma and the need to use emergency medications (short-acting inhaled beta-2 agonists) to stop seizures. Patients with confirmed allergies to acetylsalicylic acid and other NSAIDs should not take these medications during treatment with Singulair, since Singulair, while improving respiratory function in patients with allergic bronchial asthma, cannot completely prevent their NSAID-induced bronchoconstriction. The dose of inhaled corticosteroids used simultaneously with the drug Singulair can be gradually reduced under the supervision of a doctor, but a sharp replacement of inhaled or oral corticosteroids with the drug Singulair can not be carried out. Neuropsychiatric disorders have been reported in patients treated with Singulaire. Given that these symptoms may have been caused by other factors, it is not known whether they are related to taking the drug Singulair. The doctor should discuss these side effects with patients and/or their parents / guardians. Patients and/or their caregivers should be advised that if such symptoms occur, they should inform the attending physician. Reducing the dose of systemic corticosteroids in patients receiving anti-asthmatic agents, including leukotriene receptor blockers, was accompanied in rare cases by one or more of the following reactions: eosinophilia, rashes, worsening of pulmonary symptoms, cardiological complications and/or neuropathy, sometimes diagnosed as Charge-Strauss syndrome, systemic eosinophilic vasculitis. Although the causal relationship of these adverse reactions with leukotriene receptor antagonist therapy has not been established, caution should be exercised and appropriate clinical monitoring should be carried out when reducing the dose of systemic corticosteroids in patients receiving Singulair. 10 mg coated tablets contain lactose monohydrate. Patients with a rare form of hereditary galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption should not be prescribed Singulair in this dosage form. Influence on the ability to drive vehicles and work with mechanisms.

There are no data indicating that taking the drug Singulair affects the ability to drive a car or moving mechanisms. Use in patients with liver function disorders

No special dose adjustment is required for patients with mild or moderate hepatic impairment. There are no data on the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale). Use in patients with impaired renal function

No special dose adjustment is required for patients with renal insufficiency. Use in children

Contraindication: children under 6 years of age. Children aged 6 to 14 years are prescribed a dose of 5 mg (1 tab. chewing gum)/day. No dose adjustment is required for this age group. Use in elderly patients

For elderly patients, no special dose adjustment is required.

Product form

28 pcs. in a package: 4 blisters of 7 pcs. The pack is cardboard.

Storage conditions

The drug should be stored out of the reach of children, protected from moisture and light at a temperature not exceeding 30°C. Shelf life-3 years.

Active ingredient

Montelukast

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

Bronchospasm, Bronchial asthma