Moncasta - instructions for use, doses, side effects, contraindications

² Film-forming mixture: hypromellose 71.714%, titanium dioxide (E171) 15.936%, talc 6.972%, propylene glycol 4.980%, iron dye oxide yellow (E172) 0.332%, ferric oxide red oxide (E172) 0.066%.

Description:

Round, slightly biconcave tablets covered with a film coat of pale pink color, with a facet on both sides.

View of the fracture: a rough mass of white or almost white with a filmy coating of pale pink.

Pharmacotherapeutic group:Leukotriene receptor blocker

ATX: & nbsp

R.03.D.C.03 Montelukast

Pharmacodynamics:

Cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are strong inflammatory mediators - eicosanoids, which are excreted by different cells, including mast cells and eosinophils. These important proastmatic mediators are associated with cysteinyl leukotriene (CysLT) receptors. CysLT Type 1 receptors (CysLT₁receptors) 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 (CysLTs) correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, increased mucus secretion, increased vascular permeability, and an increase in the number of eosinophils. With allergic rhinitis after exposure to an allergen, release occurs CysLTs from proinflammatory cells of the mucous membrane of the nasal cavity during the early and late phases of the allergic reaction, which is manifested by the symptoms of allergic rhinitis. With an intranasal assay with CysLTs increased resistance of the nasal airways and symptoms of nasal obstruction was demonstrated.

Montelukast - highly active when administered a drug that significantly improves the rates of inflammation in bronchial asthma. According to biochemical and pharmacological analysis montelukast with high affinity and selectivity is associated with CysLT₁receptors without interacting with other pharmacologically important receptors in the airways (such as prostaglandin, cholinergic or p-adrenergic receptors). Montelukast inhibits physiological action LTC₄, LTD₄ and LTE₄ by binding to CysLT₁ receptors, without exerting a stimulating effect on these receptors.

Montelukast inhibits CysLT₁-receptors in the respiratory tract, which is confirmed by the ability to block the development of bronchospasm in response to inhalation LTD₄ in patients with bronchial asthma. Doses of 5 mg are sufficient for arresting bronchospasm induced LTD₄.

Montelukast causes bronchodilation within 2 hours after ingestion and may supplement the bronchodilation caused by β₂-adrenomimetics.

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

Pharmacokinetics:

Suction

Montelukast quickly and almost completely absorbed after ingestion. In adult patients with fasting tablets coated with a film coat, 10 mg maximum concentration (C_m_Oh) is achieved after 3 hours (T_m_Oh). The average bioavailability with oral administration is 64%. Eating does not affect C_m_Oh in blood plasma and bioavailability of the drug.

Distribution

Montelukast binds to plasma proteins more than 99%. The volume distribution of Montelukast in a state of equilibrium concentration averages 8-11 liters. Studies with radiolabeled Montelukast performed on rats indicate minimal penetration through the blood-brain barrier. In addition, concentrations of labeled montelukast 24 hours after administration were minimal in all other tissues.

Metabolism

Montelukast is actively metabolized. In the study of therapeutic doses in adults and children, the concentration of montelukast metabolites in the equilibrium state in plasma is not determined.

Research in vitro using human liver microsomes showed that the isoenzymes of the cytochrome P450: 3A4, 2C8 and 2C9 system participate in the metabolism of montelukast.According to the results of studies carried out in conditions in vitro in microsomes of human liver, montelukast in the therapeutic concentration in the blood plasma does not inhibit the isoenzymes of the cytochrome P450 system: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

Excretion

Plasma clearance of montelukast in healthy adults is an average of 45 ml / min. After ingestion of radioactively labeled montelukast, 86% of its quantity is excreted with feces for 5 days and less than 0.2% in urine, which confirms that montelukast and its metabolites are excreted almost exclusively with bile.

The half-life (T_1/2) montelukast in young healthy adults is from 2.7 to 5.5 hours. The pharmacokinetics of montelukast retains a practically linear character when administered in doses over 50 mg. When taking montelukast in the morning and evening hours, there is no difference in pharmacokinetics. When 10 mg montelukast is administered 1 time a moderate (about 14%) cumulation of the active substance in the plasma is observed.

Special patient groups

Floor

The pharmacokinetics of montelukast in women and men is similar.

Elderly patients

With a single oral administration of 10 mg montelukast, the pharmacokinetic profile and bioavailability are similar in elderly and younger patients. T_1/2Montelukast from blood plasma is somewhat longer in elderly patients. Correction of the dose of montelukast in elderly patients is not required.

Race

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

Liver failure

In patients with hepatic insufficiency of mild and moderate severity and clinical manifestations of cirrhosis, a decrease in metabolism of montelukast was noted, accompanied by an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) approximately 41% after a single administration of montelukast in a dose of 10 mg. The excretion of montelukast in these patients is slightly increased in comparison with healthy subjects (mean half-life is 7.4 hours). Changes in the dose of montelukast for patients with mild to moderate hepatic insufficiency are not required. There is no data on the character of the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale).

Renal insufficiency

Because the montelukast and its metabolites are not excreted by the kidneys,pharmacokinetics of montelukast in patients with renal insufficiency was not evaluated. Correction of the dose of montelukast for this group of patients is not required.

Indications:

- Prophylaxis and long-term treatment of bronchial asthma in adults and children from the age of 15, including prevention of day and night symptoms of the disease, treatment of bronchial asthma in patients with increased sensitivity to acetylsalicylic acid and prevention of bronchospasm caused by physical exertion.

- Cupping of day and night symptoms of seasonal and / or allergic rhinitis all year round in adults and children from 15 years of age.

Contraindications:

Hypersensitivity to any of the components of the drug.

Children up to 15 years.

Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.

Pregnancy and lactation:

Pregnancy

Clinical studies of the preparation Moncasta ® with the participation of pregnant women were not conducted. Moncaste® should be used during pregnancy and during breastfeeding only if the expected benefit to the mother exceeds the potential risk to the fetus or child.During the post-marketing application of montelukast, the development of birth defects in the limbs of newborns whose mothers were taken montelukast during pregnancy. Most of these women also took other medications to treat bronchial asthma during pregnancy. The causal relationship between the administration of montelukast and the development of birth defects of the limbs has not been established.

Breastfeeding period

It is not known whether Moncast® is excreted in breast milk. Because many drugs are excreted in breast milk, this should be taken into account when administering Moncast® during breastfeeding.

Dosing and Administration:

Inside, 1 time per day, regardless of time of food intake.

For treatment bronchial asthma Moncast® should be taken in the evening.

For treatment allergic rhinitis the preparation Moncasta ® 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 pill Moncasta ® once a day, in the evening.

Adults and children aged 15 years and over

The dose for adults and children over 15 years is 1 tablet, film-coated, 10 mg per day.

General recommendations

The therapeutic effect of Moncast® on the parameters that reflect the course of bronchial asthma develops during the first day. Patient should continue take the drug Moncast® as in the period of achieving control over the symptoms of bronchial asthma, and during periods of exacerbation of bronchial asthma.

For elderly patients, patients with renal insufficiency, as well as patients with impaired liver function of mild and moderate severity, and also, depending on gender, special dose selection is not required.

Moncast application® simultaneously with other types of treatment of bronchial asthma

The drug Moncasta ® can be added to the treatment of the patient with bronchodilators and inhaled glucocorticosteroids (see section "Interaction with other drugs").

Side effects:

In general, the preparation of Moncasta® is well tolerated. Side effects are usually mild and, as a rule, do not require withdrawal of the drug. The overall incidence of side effects with Moncast® is comparable to that of placebo.

Children aged 2 to 5 years with bronchial asthma

In clinical studies of Montelukast, 573 patients aged 2 to 5 years took part. In a 12-week, placebo-controlled clinical trial, the only adverse event (AE) estimated to be associated with taking the drug was observed in> 1% of patients taking montelukast, and more often than in the group of patients taking placebo, there was a thirst. 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 Montelukast for at least 3 months, 230 patients for 6 months or longer, and 63 patients for 12 months or longer. With longer treatment, the profile of AE did not change.

Children aged 2 to 14 years with seasonal allergic rhinitis

In a 2-week, placebo-controlled clinical trial using montelukast for the treatment of seasonal allergic rhinitis, 280 patients aged 2 to 14 years took part. Montelukast was taken by patients once a day in the evening and was generally well tolerated, the safety profile of Montelukast was similar to the placebo safety profile.In this clinical trial, AEs that were considered to be drug-related were not recorded would be observed in ≥1% of patients taking montelukast, and more often than in the group of patients taking placebo.

Children aged 6 to 14 years with bronchial asthma

The safety profile of Montelukast in children was generally similar to that of adults and was comparable to the placebo safety profile.

In an 8-week, placebo-controlled clinical trial, a single AE, estimated to be associated with drug intake, was observed in> 1% of patients taking montelukast, and more often than in the group of patients taking placebo, there was a headache. The frequency difference between the two treatment groups was statistically insignificant.

In studies to assess the rate of growth, the safety profile of patients of this age group was consistent with the previously described safety profile of montelukast.

With longer treatment (more than 6 months), the profile of AE did not change.

Adults and children aged 15 years and older with bronchial asthma

In two 12-week, placebo-controlled clinical trials with a similardesign only AEs evaluated as related to taking the drug, observed in ≥1% of patients taking montelukast, and more often than in the group of patients taking placebo, there were abdominal pain and headache. Differences in the frequency of AE data between the two treatment groups were statistically insignificant. With longer treatment (within 2 years), the profile of AE did not change.

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

Montelukast was taken by patients once or twice a day in the morning or in the evening and was generally well tolerated, the drug safety profile was similar to the placebo safety profile. In placebo-controlled clinical trials, AEs that were considered to be drug-related were not reported would be observed in ≥1% of patients taking montelukast, and more often than in the group of patients taking placebo. In a 4-week, placebo-controlled clinical trial, the safety profile of Montelukast was similar to that in a 2-week study. The incidence of drowsiness with montelukast in all studies was the same as with placebo.

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

Montelukast was taken by patients 1 time per day and was generally well tolerated. The drug safety profile was similar to the safety profile observed in the treatment of patients with seasonal allergic rhinitis and with placebo. In these clinical trials, AEs that were considered to be associated with drug intake were not recorded, would be observed in ≥1% of patients, who took montelukast, and more often than in the group of patients taking placebo. The incidence of drowsiness with montelukast was the same as with placebo.

Generalized analysis of the results of clinical trials

A generalized analysis of 41 placebo-controlled clinical trials was conducted (35 trials involving patients aged 15 years and older, 6 trials involving patients aged 6 to 14 years) using approved methods for assessing suicidality. Among 9929 patients who took montelukast, and 7780 patients taking placebo in these studies, one patient was identified with suicidal tendencies in the group of patients taking montelukast. In none of the treatment groups were there any suicides, suicidal attempts or other preparatory actions that indicated suicidal behavior.

Separately, a generalized analysis of 46 placebo-controlled clinical trials (35 trials involving patients aged 15 years and older, 11 studies involving patients aged 3 months to 14 years) was conducted to evaluate adverse behavioral effects (NPEs). Among the 11673 patients taking in these studies montelukast, and 8827 patients taking placebo, the percentage of patients with at least one NPE was 2.73% among those taking montelukast, and 2.27% among those taking placebo, the odds ratio was 1.12 (95% confidence interval [0.93, 1.36]).

Classification of the incidence of side effects recommended by the World Health Organization (WHO):

very often ≥1 / 10

often from ≥ 1/100 to <1/10

infrequently from ≥ 1/1000 to <1/100

rarely from ≥ 1/10000 to <1/1000

very rarely <1/10000

the frequency of the unknown can not be estimated from the available data.

During the post-marketing use of montelukast, the following identified N:

Infectious and parasitic diseases: very often: infections of the upper respiratory tract.

Violations from the blood and lymphatic system: rarely: increased propensity to bleed; frequency unknown: thrombocytopenia.

Immune system disorders: infrequently: hypersensitivity reactions, including anaphylaxis; very rarely: eosinophilic liver infiltration.

Disorders of the psyche: infrequently: agitation, including aggressive behavior or hostility, anxiety, depression, pathological dreams, insomnia, psychomotor activity (including irritability, anxiety and tremor), somnambulism; very rarely: hallucinations, disorientation, suicidal ideation and behavior (suicidal); frequency unknown: impaired attention, memory impairment.

Impaired nervous system: infrequently: dizziness, drowsiness, paresthesia / hypoesthesia; very rarely: convulsions.

Heart Disease: rarely: heart palpitations.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently: nosebleeds; very rarely: pulmonary eosinophilia.

Disorders from the digestive system: often: diarrhea, nausea, vomiting, pancreatitis; infrequently: indigestion.

Disorders from the liver and bile ducts: often: increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) in the blood plasma; very rarely: hepatitis (including cholestatic, hepatocellular and mixed liver damage).

Disturbances from the skin and subcutaneous tissues: often: rashes; infrequent: a tendency to form a hematoma, a skin itch, urticaria; rarely: angioedema; very rarely: erythema nodosum, erythema multiforme.

Disturbances from the musculoskeletal and connective tissue: infrequently: arthralgia, myalgia, including muscle cramps.

Disorders from the kidneys and urinary tract: frequency unknown: enuresis in children.

General disorders and disorders at the site of administration: infrequently: asthenia (weakness) / fatigue, swelling, pyrexia.

Overdose:

There is no specific information on the treatment of overdose with Montelukast.

In clinical studies of long-term (22 weeks) treatment of adult patients with bronchial asthma with daily doses of montelukast up to 200 mg, or during short (about 1 week) clinical studies with daily doses up to 900 mg of overdose symptoms were not observed.

There have been cases of acute overdose (reception of at least 1000 mg per day) by Montelukast during the post-registration period and during clinical trials in adults and children. Clinical and laboratory data indicated the comparability of the safety profiles of Montelukast 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 Moncast®.

Treatment for acute overdose is symptomatic.

There is no data on the effectiveness of peritoneal dialysis or hemodialysis.

Interaction:

Moncast® can be administered together with other medications that are commonly used to prevent and prolong treatment of bronchial asthma and / or treat 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.

Value AUC Montelukast decreases with simultaneous admission phenobarbital by about 40%, but this does not require a change in the dosage regimen of Moncast®.

In studies in vitro determined that montelukast inhibits isoenzyme CYP2C8, However, in the study of the drug interaction of montelukast and rosiglitazone (metabolized with the participation of isoenzyme CYP2C8) in conditions in vivo it was shown that montelukast did not inhibit isoenzyme CYP2C8. Thus, it is not assumed effects of montelukast on CD2C8-mediated metabolism of medications (for example, paclitaxel, rosiglitazone, repaglinide).

Research in vitro showed that montelukast is a substrate of isoenzymes CYP2C8, CYP2C9 and CYP3A4. Data from the clinical study of drug interactions for montelukast and gemfibrozil (an inhibitor of both isoenzyme CYP2C8, and isoenzyme CYP2C9) demonstrate that gemfibrozil increases the effect of systemic effects of Montelukast 4.4 times. Simultaneous reception itraconazole, powerful inhibitor of isoenzyme CYP3A4, together with gemfibrozil and montelukast did not lead to an additional increase in the effect of systemic exposure to montelukast. Impact gemfibrozil the systemic effect of montelukast can not be considered clinically significant on the basis of safety data when administered at doses exceeding the approved dose of 10 mg for adult patients (eg, when administered at a dose of 200 mg / day for adult patients for 22 weeks and up to 900 mg / day for about one week there were no clinically significant negative effects). Thus, with simultaneous administration with gemfibrozilom correction of the dose of montelukast is not required. Based on research results in vitro no clinically significant drug interactions with other known isozyme inhibitors CYP2C8 (e.g., from trimethoprim). In addition, simultaneous reception of Montelukast with only one itraconazole did not lead to a significant increase in the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators

The preparation Moncasta® is a justified addition to monotherapy with bronchodilators if the latter do not provide adequate control of bronchial asthma. Upon achievement of the therapeutic effect of drug treatment Moncasta® can start a gradual reduction in the dose of bronchodilators.

Combined treatment with inhaled glucocorticosteroids

Treatment with Moncast® provides an additional therapeutic effect to patients who use inhaled glucocorticosteroids. Once the stabilization of the condition is achieved, a gradual decrease in the dose of the glucocorticosteroid can be started under the supervision of the physician. In some cases, complete cancellation of inhaled glucocorticosteroids is permissible, but a sharp replacement of inhaled glucocorticosteroids by Moncast® is not recommended.

Special instructions:

The effectiveness of the preparation Moncasta for oral administration for the treatment of acute attacks of bronchial asthma is not established, therefore, the preparation of Moncasta ® in tablets is not recommended for the treatment of acute attacks of bronchial asthma. Patients should be instructed to always have emergency medication to relieve asthma attacks (short-acting inhaled beta-2 agonists).

Do not stop taking Moncast® during the period of asthma exacerbation and the need for emergencyrelief of seizures (short-acting inhaled beta-2 agonists).

Patients with a confirmed allergy to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during the treatment with Moncast®, as the preparation of Moncasta improves respiratory function in patients with allergic bronchial asthma, nevertheless can not completely prevent them caused by NSAID bronchoconstriction.

The dose of inhaled glucocorticosteroids used concomitantly with the preparation of Moncast® can be gradually reduced under the supervision of a doctor, however, a sharp substitution of inhaled glucocorticosteroids or glucocorticosteroids for ingestion with Moncast® preparation can not be carried out. In patients who took montelukast, psychoneurological disturbances have been described (see the "Side effect" section). Given that these symptoms may have been caused by other factors, it is not known whether they are associated with taking Moncast®. The physician should discuss the AE data with patients and / or their parents / guardians. Patients and / or their parents / guardians should explain that in case of such symptoms it is necessary to inform the attending physician about it.

In rare cases, patients treated with anti-asthma drugs, including leukotriene receptor antagonists experienced one or more adverse events of the following: eosinophilia, rash, worsening pulmonary symptoms, cardiac complications and / or neuropathy, sometimes diagnosed as Chardzhev-Strauss syndrome, systemic eosinophilic vasculitis. These cases were sometimes associated with a reduction in dose or cancellation glucocorticosteroid therapy for ingestion. Although the causation of these AEs therapy with antagonists of leukotriene receptors has not been established in patients taking the drug Monkasta®, care must be taken in such patients must carry appropriate clinical observation.

Special information on excipients

Monkasta® drug coated tablets, containing 10 mg of lactose, however should not be used under the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Use in elderly patients

Differences in the efficacy and safety profiles of Moncast®, associated with the age of patients, have not been identified.

Effect on the ability to drive transp. cf. and fur:

It is not expected that the use of Moncast® will affect the ability to drive vehicles and work with mechanisms. Nevertheless, individual reactions to the drug may be different. Some side effects (such as dizziness and drowsiness) that have been reported to occur very rarely with Moncast® may affect the ability of some patients to drive vehicles and work with mechanisms.

Form release / dosage:

Tablets, film-coated, 10 mg.

Packaging:

For 7 or 14 tablets in a blister of the combined material OPA / Al / PVC and aluminum foil.

1, 2, 4 blisters (7 tablets each); 1, 2 blisters (14 tablets each), along with instructions for use, are placed in a cardboard pack.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003166/09

Date of registration:24.04.2009 / 09.02.2016

Expiration Date:Unlimited

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA POLSKA, Sp.z.o.o Poland

Information update date: & nbsp13.06.2018

Illustrated instructions

Instructions

Moncasta® (Monkasta®)