Singulair pills chewable 4mg, 28pcs

Composition

1 coated tablet, contains: Active ingredient: montelukast – 4 mg; Excipients: microcrystalline cellulose, lactose, sodium croscarmellose, hyprolose, magnesium stearate. Composition of the shell covering the tablet: hyprolose, hypromellose, titanium dioxide, iron oxide red and iron oxide yellow dyes and Carnauba wax.

Pharmacological action

Pharmacotherapeutic group: Leukotriene receptor blocker: R. 03. D. C. 03 Pharmacodynamics :

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are strong mediators of inflammation by 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 symptoms of nasal obstruction.

Montelukast is a highly active drug when taken orally, which significantly improves the indicators of inflammation in bronchial asthma. According to the biochemical and pharmacological analysismontelukast binds with high affinity and selectivity to CysLT1 receptors, without interacting with other pharmacologically important receptors in the respiratory tract (such as prostaglandin, cholinergic or (?- adrenergic receptors).

Montelukast inhibits the physiological action of cysteinyl leukotrienes LTC4, LTD4, and LTE4 by binding to CysLT1 receptors without stimulating 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 ingestion and may supplement bronchodilation caused by ?2-adrenomimetics.

The use of montelukast in doses exceeding 10 mg per day, taken once, does not increase the effectiveness of the drug.

Pharmacokinetics:

Suction

Montelukast is rapidly and almost completely absorbed after oral use. In adults, when taking 10 mg coated tablets on an empty stomach, the maximum concentration (Cmax) is reached after 3 hours (Tmax). The average oral bioavailability is 64%. Food intake does not affect the Cmax in blood plasma and bioavailability of the drug.

Distribution

Montelukast binds to plasma proteins by more than 99%. The volume of distribution of montelukast at equilibrium concentration averages 8-11 liters.

Studies with radioactively labeled montelukast conducted on rats indicate minimal penetration through the blood-brain barrier. In addition, labeled drug concentrations were minimal in all other tissues 24 hours after use.

Metabolism

Montelukast is actively metabolized. When studying therapeutic doses in adults and children, the concentration of montelukast metabolites at steady state in plasma is not determined.

In vitro studies using human liver microsomes showed that in the metabolism of montelukast participate isoenzymes of cytochrome P-450: 3 And 4,2 and 8 2 9. According to the results of studies carried out in vitro in human liver microsomes, montelukast in therapeutic concentrations in blood plasma does not inhibit isozymes of the cytochrome P-450: 3 And 4,2,9,1A2,2 And 6,2 and 19, and 2D6.

Deduction

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.

The elimination half-life of montelukast in young healthy adults is 2.7 to 5.5 hours. 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. When taking 10 mg of montelukast 1 time a day, moderate (about 14%) accumulation of the Active ingredient in plasma is observed.

Features of pharmacokinetics in retail groups of patients

The

pharmacokinetics of montelukast are similar in women and men.

Elderly patients

With a single oral dose of 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in the elderly and young patients. The plasma half-life of montelukast is somewhat longer in older adults. Dose adjustment of the drug in the elderly is not required.

Race

There were no differences in clinically significant pharmacokinetic effects in patients with different races.

Liver failure

In patients with mild to moderate hepatic insufficiency and clinical manifestations of cirrhosis, a slowdown in the metabolism of montelukast was observed, accompanied by an increase in the area under the pharmacokinetic curve “concentration – time” (AUC) by approximately 41% after a single dose of the drug in a dose of 10 mg. The elimination of montelukast in these patients is slightly increased compared to healthy subjects (the average elimination half-life 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).

Kidney failure

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 for this group of patients.

Indications

• Prevention and long-term treatment of bronchial asthma in children aged 2 years and older: to control day and night symptoms of the disease;

• Relief of allergic rhinitis symptoms in children aged 2 years and older.

Contraindications

• Children under 2 years of age;
• Phenylketonuria;
• Hypersensitivity to the components of the drug.

Side effects

In general, Singulaire® is well tolerated. Side effects are usually mild and mild. as a rule, they do not require drug withdrawal. The overall incidence of adverse events during treatment 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 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 patients were treated for 6 months or longer, and 63 patients were treated 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 Singulair® for the treatment of seasonal allergic rhinitis. Singulair® was taken by patients once a day in the evening and was generally well tolerated, the safety profile of the drug was similar to that of placebo.

No AES were reported in this clinical trial. which would be considered drug – related, would be observed in ?1% of patients treated with 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 AES assessed as drug-related were observed in patients with the same type of cancer. ?1% of patients treated with Singulair®, and more often than in the placebo group, had abdominal pain and headache.

The differences in the frequency of these AES between the two treatment groups were statistically insignificant. With longer treatment (for 2 years), the AES profile did not change.

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

Singulair® was administered to patients once a day in the morning or evening and was generally well tolerated, with a safety profile similar to that of placebo. In placebo-controlled clinical trials, no AES were reported that would be considered drug-related, would be observed 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

The drug Singulair® was taken by patients once a day and 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 21% of patients taking Singulair®, and more often than in the group of patients taking 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, one patient with suicidal tendencies was identified in the group of patients taking 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 (APES). Among all 1,673 patients treated with Singulair® and 8,827 patients treated with placebo in these studies, the percentage of patients with at least one NPE was 2.73% among those taking Singulair® and 2.27% among those taking placebo: the odds ratio was 1.12(95% confidence interval [0.93; 1.361).

During post-marketing use of the drug, the following AES were reported:

infectious and parasitic diseases: upper respiratory tract infections;

blood and lymphatic system disorders: increased tendency to bleed, thrombocytopenia;

immune system disorders: hypersensitivity reactions, including anaphylaxis, very rarely (<1 / 10000) eosinophilic liver infiltration;

mental disorders: agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, attention disorders, abnormal 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 (<1/10000) seizures;

cardiac disorders: rapid heartbeat;

respiratory, thoracic and mediastinal disorders: nosebleeds, pulmonary eosinophilia;

gastrointestinal disorders: diarrhea, dyspepsia, nausea, vomiting, pancreatitis;

liver and biliary tract disorders: increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) in the blood, very rarely (<1 /10000) hepatitis (including cholestatic, hepatocellular and mixed liver lesions);

disorders of the rut and subcutaneous tissues: angioedema, tendency to form hematomas, erythema nodosum, erythema multiforme, pruritus, rash, urticaria;

musculoskeletal and connective tissue disorders: arthralgia, myalgia, including muscle cramps:

kidney and urinary tract disorders: enuresis in children;

general disorders and disorders at the injection site: asthenia (weakness)/fatigue, swelling, pyrexia.

Interaction

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

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

In vitro studies have shown that montelukast inhibits the CYP 2 C8 isoenzyme of the cytochrome P450 system, but in an in vivo drug interaction study of montelukast and rosiglitazone (metabolized with the participation of the CYP 2 C8 isoenzyme of the cytochrome P450 system), it was shown that montelukast did not inhibit the CYP 2 C8 isoenzyme. Thus, montelukast is not expected to affect CYP 2 C8-mediated drug metabolism drugs (for example, paclitaxel, rosiglitazone, repaglinide).

In vitro studies have shown that montelukast is a substrate of CYP2C8 isoenzymes. 2 C 9 and 3 A 4. Data from a clinical drug interaction study with montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2 C 9) demonstrate that gemfibrozil increases the effect of montelukast systemic exposure 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, when used at a dose of 200 mg/day for adult patients for 22 weeks and up to 900 mg/day 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 9 results of in vitro studies, no clinically significant drug interactions with other known CYP2C8 inhibitors (for example, trimethoprim) are expected. In addition, co-use of montelukast with itraconazole alone did not significantly increase the effect of systemic exposure to montelukast.

Combined cookies with bronchodilators

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

Combined treatment with inhaled glucocorticosteroids

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

How to take, course of use and dosage

Inside 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 at the request of the patient.

Patients with bronchial asthma and allergic rhinitis should take 1 tablet of Singulair® once a day in the evening.

Children aged 2 to 5 years

For bronchial asthma and / or allergic rhinitis – 1 chewable tablet of 4 mg per day.

General recommendations

The 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 Singulair ® concomitantly with other types of treatment for bronchial asthma

Singulair® can be added to the patient’s treatment with bronchodilators and inhaled corticosteroids.

Overdose

There is no specific information about the treatment of overdose with Singulair®. No symptoms of overdose were observed in clinical studies of long-term (22 weeks) treatment of adult patients with bronchial asthma with daily doses of Singulair® up to 200 mg, or in short (about 1 week) clinical studies with daily doses up to 900 mg.

There have been cases of acute overdose (taking at least 1000 mg of the drug per day) with Singulair® 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 side effects were thirst, drowsiness, vomiting, psychomotor agitation, headache, and abdominal pain. These side effects are consistent with the safety profile of Singulair.

Treatment in case of acute overdose is symptomatic.

There are no data on the effectiveness 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, so the drug 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 Singulair® during the period of acute asthma and the need for emergency medications to stop seizures (short-acting inhaled beta-2 agonists).

Patients with confirmed allergies to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs 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 glucocorticosteroids used concomitantly with Singulair® can be gradually reduced under the supervision of a doctor, but an abrupt replacement of inhaled or oral glucocorticosteroids with Singulair® should not be carried out.

Neuropsychiatric disorders have been reported in patients treated with Singulair® (see the section “Side effects”). Given that these symptoms may have been caused by other factors, it is not known whether they are associated with taking Singulair®. The doctor should discuss these AES with patients and/or their parents / guardians. Patients and/or their parents/guardians should be advised that if such symptoms occur, they should inform the attending physician.

In rare cases, patients treated with anti-asthmatic medications, including leukotriene receptor antagonists, have experienced one or more of the following AES: eosinophilia, rash, worsening of pulmonary symptoms, cardiac complications, and/or neuropathy, sometimes diagnosed as Charge-Strauss syndrome, systemic eosinophilic vasculitis.

These cases were sometimes associated with dose reduction or discontinuation of oral glucocorticoid therapy. Although the causal relationship of these AES with leukotriene receptor antagonist therapy has not been established, caution should be exercised in patients taking Singulaire®: appropriate clinical monitoring should be carried out in such patients.

Singulair ® film-coated tablets,10 mg contains lactose monohydrate. Patients with a rare form of hereditary galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption should not take Singulair ® 10 mg coated tablets.

Use in elderly patients

There were no age-related differences in the efficacy and safety profiles of Singulair®.

Impact on the ability to drive a vehicle :

It is not expected that the use of Singulaire® will affect the ability to drive vehicles and work with mechanisms. However, individual reactions to the drug may vary. Some side effects (such as dizziness and drowsiness), which have been reported very rarely with Singulair®, may affect the ability of some patients to drive vehicles and operate machinery.

Storage conditions

The drug should be stored out of the reach of children, dry, protected from light at a temperature of 15° to 30°C.

Shelf

life is 2 years.

Active ingredient

Montelukast

Conditions of release from pharmacies

By prescription

Dosage form

chewable tablets

Purpose

Adults as prescribed by a doctor

Indications

Bronchospasm, Bronchial asthma