Montelukast - instructions for use, dose, side effects, contraindications

Excipients: mannitol 203.3 mg; cellulose microcrystalline - 81.0 mg; giprolose (hydroxypropylcellulose) 3.0 mg; magnesium stearate - 3.0 mg; flavoring Cherry - 3.0 mg; aspartame - 1.5 mg.

Description:Round biconvex tablets white or almost white with the smell of cherries.

Pharmacotherapeutic group:Anti-inflammatory anti-bronchoconstrictive agent - leukotriene peer reviewer

ATX: & nbsp

R.03.D.C.03 Montelukast

Pharmacodynamics:

Cysteinyl-leukotrienes (LTC₄, LTD₄, LTE₄) are strong mediators of inflammation - eicosanoids, which are excreted by different cells, including mast cells and eosinophils. These important proastmatic mediators are linked to the cystenile leukotriene receptors. Cysteinyl leukotriene 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 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. In case of allergic rhinitis after exposure to the allergen, cysteinyl leukotrienes are released from the proinflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which is manifested by the symptoms of allergic rhinitis. With an intranasal test with cysteinyl leukotrienes, an increase in the resistance of the airways and the 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, a drug with high selectivity and chemical affinity binds to CysLT₁ receptors (instead of other pharmacologically important respiratory tract receptors, such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiological action of LTC cysteinyl leukotrienes₄, LTD₄, LTE₄ by binding to CysLT₁receptors, without exerting a stimulating effect on these receptors.

Montelukast inhibits CysLT₁-receptors of the epithelium of the respiratory tract, due to this reduces the bronchospasm caused by the inhalation of cysteinyl leukotriene LTD₄) in patients with bronchial asthma. Doses of 5 mg are sufficient for arresting bronchospasm induced by LTD₄.

Montelukast causes bronchodilation within two hours after ingestion and may supplement the bronchodilation induced 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. When taking fasting tablets chewing 5 mg maximum concentration in blood plasma (C_max) Adults are reached after 2 hours.The average bioavailability with oral administration is 73%.

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 performed on rats with radiolabeled Montelukast indicate a minimal penetration through the blood-brain barrier. In addition, the concentration of labeled Montelukast 24 hours after administration was minimal in all other tissues.

Metabolism

Montelukast is actively metabolized. In the study of therapeutic doses 5 the state of equilibrium concentration in blood plasma in adults and children, the concentration of metabolites of montelukast is not determined.

In vitro studies using human liver microsomes have shown that cytochrome P450 isoenzymes CYP: 3A4, 2A6, 2C8 and 2C9 are involved in the metabolism of montelukast. According to further research conducted in vitro in human liver microsomes, the therapeutic concentration of montelukast in blood plasma does not inhibit cytochrome P450 isoenzymes CYP: 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 through the intestine within 5 days and less than 0.2% by the kidneys, which confirms that montelukast and its metabolites are excreted almost exclusively with bile. The half-life of montelukast in young healthy adults ranges 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 receiving 10 mg of montelukast, a moderate (about 14%) cumulation of the active substance in the blood plasma is observed once a day.

Peculiarities of pharmacokinetics in different 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 patients and young patients. Period

half-life of montelukast from blood plasma is somewhat greater in elderly patients.Correction of the dose of the drug 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 montelukast metabolism was noted, accompanied by an increase in the area under the pharmacokinetic concentration-time curve (AUC) by approximately 41% after a single dose of 10 mg. The half-life of montelukast in these patients is slightly increased (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 through the kidneys, pharmacokinetics of montelukast in patients with renal insufficiency has not been evaluated. A dose adjustment for this group of patients is not required.

Indications:

- Prophylaxis and long-term treatment of bronchial asthma, including prevention of day and night symptoms of the disease;

- treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid;

- prevention of bronchospasm caused by physical exertion;

- relief of day and night symptoms of seasonal allergic rhinitis and persistent allergic rhinitis.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- children's age till 6 years;

- phenylketonuria.

Pregnancy and lactation:

Clinical studies of montelukast with the participation of pregnant women have not been conducted. A drug Montelukast should be used during pregnancy and during lactation, only if the expected benefit for 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 for the treatment of bronchial asthma and the period of pregnancy.The causal relationship between the administration of montelukast and the development of birth defects of the limbs has not been established.

It is not known whether montelukast with breast milk. Since many drugs are excreted in breast milk, it is necessary to take this into account when prescribing the drug Montelukast breastfeeding women.

Dosing and Administration:

A drug Montelukast take inside once a day, regardless of food intake. The tablet can be swallowed whole or chewed before swallowing. For treatment of bronchial asthma, the drug should be taken in the evening. In the treatment of allergic rhinitis, the drug can be taken at any time of the day. Patients with bronchial asthma and allergic rhinitis should take one tablet once a day in the evening.

Children aged 6 to 14 years

One tablet chewing 5 mg once a day.

The choice of dose for this age group is not required.

Adults and teens from age 15

The dose for adults and children over 15 years is 10 mg montelukast once a day. Therapeutic effect of the drug Montelukast on the indicators reflecting the course of bronchial asthma, develops during the first day.The patient should continue to take the drug as during the control of symptoms of bronchial asthma, and during the period of exacerbation of the disease.

Special patient groups

For elderly patients, patients with renal insufficiency, patients with impaired liver function of mild or moderate severity, dose adjustment is not required. The dose of the drug is the same for both female and male patients.

Application of the drug Montelukast simultaneously with other types of treatment of bronchial asthma

A drug Montelukast can be added to the treatment of the patient with bronchodilators and inhaled glucocorticosteroids (GCS).

Side effects:

Side effects are usually mild and, as a rule, do not require withdrawal of the drug.

Impaired nervous system: headache, dizziness, drowsiness, paresthesia / hypesthesia, convulsions.

Heart Disease: cardiopalmus.

Disturbances from the respiratory system, chest and mediastinal organs: nosebleeds, pulmonary eosinophilia.

Disorders of the psyche: agitation, including aggressive behavior or hostility, anxiety, depression,disorientation, attention disturbance, pathological dreams, hallucinations, insomnia, memory disorders, psychomotor activity including irritability, anxiety and tremor), somnambulism, suicidal thoughts and behavior (suicidal).

Disorders from the gastrointestinal tract: diarrhea, dyspepsia, nausea, vomiting, pancreatitis, abdominal pain, thirst.

Disorders from the liver and bile ducts: increased activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT), hepatitis (including cholestatic, hepatocellular and mixed liver damage).

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

Violations from the blood and lymphatic system: increased tendency to bleeding, thrombocytopenia.

Disturbances from the skin and subcutaneous tissues: tendency to form hematomas, erythema nodosum, erythema multiforme, itching, rashes, hives, angioedema.

Immune system disorders: hypersensitivity reactions, including anaphylaxis, eosinophilic liver infiltration.

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

Infectious and parasitic diseases: infections of the upper respiratory tract. General disorders and disorders at the site of administration: asthenia (weakness) / fatigue, swelling, pyrexia.

Overdose:

Symptoms

Data on symptoms of an overdose with montelukast receiving patients with bronchial asthma at a dose exceeding 200 mg per day for 22 weeks and at a dose of 900 mg per day for one week was not revealed.

There have been cases of acute overdose of montelukast (intake of at least 1000 mg per day) 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, mydriasis. abdominal pain. These side effects are consistent with the Montelukast safety profile.

Treatment

Treatment for acute overdose is symptomatic. There is no information on the specific treatment of the overdose of montelukast.There is no data on the effectiveness of peritoneal dialysis or hemodialysis.

Interaction:

Montelukast can be administered together with other medicines that are commonly 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 value of AUC of montelukast decreases with simultaneous administration of phenobarbital by about 40%, but this does not require a change in the dosage regimen of the drug Montelukast.

In vitro studies found that montelukast inhibits the isoenzyme CYP 2C8 of the cytochrome P450 system, however, in the study of the drug interaction in vivo of montelukast and rosiglitazone (metabolized with the participation of the CYP 2C8 isoenzyme of the cytochrome system), no confirmation of the inhibition of the isoenzyme CYP 2C8 by montelukas is obtained. Therefore, in clinical practice, the effect of montelukast on CYP 2C8-mediated metabolism of a number of medications, including paclitaxel, rosiglitazone, repaglipid and others, is not expected to be influenced by clinical practice.

In vitro studies have shown that montelukast is a substrate of isoenzymes CYP 2C8, 2C9 and 3A4. These clinical studies of drug interactions in relation montelukast and gemfibrozil (CYP inhibitor like 2S8 and 2S9) demonstrate that the effect of gemfibrozil increases the systemic exposure of Montelukast 4.4 times. The simultaneous administration of itraconazole, a strong inhibitor of CYP α4 isofermant, 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 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 200 mg / day for adult patients for 22 weeks and up to 900 mg / day for of patients taking the drug for about one week, there were no clinically significant adverse effects). Thus, with a co-administration with gemfibrozilom adjustment of the dose of montelukast is not required. According to the results of in vitro studies, clinically important drug interactions with other known inhibitors of the CYP 2C8 isoenzyme (for example, with trimethoprim) are not expected.In addition, the joint administration of montelukast with itraconazole alone did not result in a significant increase in the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators

Montelukast is a well-founded addition to monotherapy with bronchodilators if the latter do not provide adequate control of bronchial asthma. When the therapeutic effect is achieved against the background of therapy with montelukast, a gradual decrease in the dose of bronchodilators can be started.

Combination treatment with inhaled glucocorticosteroids Treatment with montelukast provides an additional therapeutic effect to patients who use inhaled glucocorticosteroids. When the patient's condition is stabilized, a gradual decrease in the glucocorticosteroid dose can be started under the supervision of the doctor. In some cases, complete cancellation of inhaled glucocorticosteroids is permissible, but a sharp replacement of inhaled glucocorticosteroids by montelukast Not recommended.

Special instructions:

The effectiveness of montelukast for oral administration in relation to the treatment of acute attacks of bronchial asthma has not been established. Therefore, the drug Montelukast in tablets it is not recommended to prescribe for the treatment of acute attacks of bronchial asthma.

Patients should be instructed to always have emergency medication to relieve asthma attacks (inhaled β₂agonists of short action).

Do not stop taking the drug Montelukast in the period of exacerbation of bronchial asthma. It should be remembered the need for the use of emergency drugs to stop seizures (inhalation β₂agonists of short action).

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 the drug Montelukast, because the montelukast, improving respiratory function in patients with allergic bronchial asthma, nevertheless, can not completely prevent bronchoconstriction caused by a nonsteroidal anti-inflammatory drug.

The dose of glucocorticosteroids for inhalations or for ingestion taken during the treatment with montelukast can be gradually reduced under the supervision of a doctor. However, a sharp replacement of glucocorticosteroids with the drug Montelukast to conduct it is impossible.

In patients who took montelukast, psychoneurological disturbances have been described (see the "Side effect" section). Given that these symptoms could be caused by other factors, it is not known whether they are associated with taking montelukast. The doctor should discuss this undesirable phenomenon 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 effects of the following: eosinophilia, rash, worsening pulmonary symptoms, cardiac complications and / or neuropathy, sometimes diagnosed as Churg-Strauss syndrome, (systemic eosinophilic vasculitis ). These cases have sometimes been associated with a lower dose or withdrawal of oral corticosteroid therapy. Although the causation of these unwanted phenomena with the therapy has not been ascertained antagonists of leukotriene receptors in patients receiving montelukast, care must be taken and clinical monitoring performed.

A drug Montelukast tablet chewing 5 mg contains aspartame - A source of phenylalanine. Patients with phenylketonuria should be informed that each chewable tablet contains aspartame in an amount equivalent to 0.842 mg of phenylalanine, and the preparation Montelukast 5 mg chewable tablets should not be taken in patients with phenylketonuria.

Effect on the ability to drive transp. cf. and fur:Data indicating that the administration of montelukast affects the ability to drive a car or moving machinery has not been identified. However, when the drug is used, side effects such as dizziness and drowsiness may occur. In view of this, care should be taken when driving vehicles and performing actions requiring quickness of psychomotor reactions.

Form release / dosage:Tablets chewing 5 mg.

Packaging:

10, 14, 15 or 30 tablets in a contoured cell pack of a polyvinylchloride film of light-protective and aluminum foil.

30 or 60 tablets in a can of high-density polyethylene.

1, 3 or 6 contour cell packs of 10 tablets, 1, 2 or 4 contour packs of 14 tablets, 1, 2 or 4 contourcell packs of 15 tablets, 1 or 2 contourcell packs of 30 tablets or one can together with instruction but application in a pack of cardboard.

Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C. Wound in a place inaccessible to children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002862

Date of registration:18.02.2015 / 08.11.2017

Expiration Date:18.02.2020

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp02.06.2018

Illustrated instructions

Instructions

Montelukast (Montelukast)