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

auxiliary substances (core): cellulose microcrystalline - 89.3 mg; lactose monohydrate - 89.3 mg; croscarmellose sodium - 6.0 mg; giprolose - 4.0 mg; magnesium stearate 1.0 mg;

shell: hypromellose - 1.73 mg; giprolose - 1.73 mg; titanium dioxide - 1.5 mg; ferric oxide yellow oxide - 0.036 mg; ferric oxide red oxide - 0.004 mg.

Description:Round, biconvex tablets from light yellow to brownish-yellow, with engraved "M9UT" and "10" on one side.

Pharmacotherapeutic group:Anti-inflammatory anti-bronchoconstrictive agent - leukotriene receptor blocker

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 cysteinyl 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 CysLT₁receptors (instead of other pharmacological 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 the CysLT receptors of the respiratory tract epithelium, thereby simultaneously possessing the ability to inhibit bronchospasm due to the inhalation of cysteinyl leukotriene LTD₄ in patients with bronchial asthma. The dosage of montelukast, equal to 5 mg, is sufficient for arresting the bronchospasm induced by LTD_4.

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

After oral administration montelukast quickly and almost completely absorbed. In adult patients, after taking an empty tablet on a fasted tablet, at a dose of 10 mg, the average value of the maximum concentration in the blood plasma (C_max) is achieved after 3 hours. The average value of bioavailability is 64%. The values of oral bioavailability and C_max are not violated when eating.

Distribution

Montelukast binds to plasma proteins more than 99%. The volume distribution of Montelukast 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. When using therapeutic doses, the concentration of metabolites of Montelukast in blood plasma in an equilibrium state in adults and children is not determined.

In vitro studies using human liver microsomes have shown that cytochromes P450, 3A4, 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: ZA4, 2C9, 1A2, 2A6, 209 and 2D6.

Excretion

The half-life of montelukast in young healthy adults ranges from 2.7 to 5.5 hours. The clearance of montelukast is 45 ml / min in healthy adults. After oral administration of montelukast, 86% of the total is excreted through the intestine for 5 days and less than 0.2% - with urine, which confirms that montelukast and its metabolites are excreted almost exclusively with bile.

The pharmacokinetics of the half-life of montelukast retains a nearly linear character when administered in doses over 50 mg. When taking montelukast in the morning and evening hours, there is no difference in pharmacokinetics. With the administration of 10 mg of montelukast per day, a moderate (about 14%) cumulation of the active substance in the blood plasma is observed.

Peculiarities of pharmacokinetics in different patient groups

Floor

The pharmacokinetics of montelukast in women and men is similar.

Age

With a single oral administration of 10 mg montelukast, the pharmacokinetic profile and bioavailability are similar in elderly patients and young patients. The half-life of montelukast from blood plasma is somewhat greater in elderly patients. Correction of dose of the drug in elderly patients is not required.

Ethnicity

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 excretion of montelukast in these patients is slightly increased in comparison with healthy subjects (mean elimination 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 in the urine, the 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) in adults and children over 15 years of age;

- 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 in adults and children over 15 years of age.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- children's age till 15 years;

- Due to the presence of lactose monohydrate (milk sugar) in the formulation, this drug is contraindicated for congenital lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Pregnancy and lactation:

Montelukast should be used during pregnancy and lactation only in cases where the expected benefit to the mother exceeds the potential risk to the fetus or child.

There were reports of the development of birth defects in the limbs of newborns whose mothers were taking 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.

It is not known whether montelukast with breast milk.

Dosing and Administration:

The drug is taken orally, without chewing, with a sufficient amount of liquid, regardless of food intake.

Children older than 15 years and adults are recommended to take 1 tablet, coated with 10 mg per day.

For the treatment of bronchial asthma montelukast should be taken in the evening. In the treatment of allergic rhinitis, the drug can be taken at any time of the day. With a combined pathology (bronchial asthma and allergic rhinitis), the drug should be taken in the evening.

The therapeutic effect of Montelukast, on the indicators reflecting the course of bronchial asthma, develops during the first day. The patient should continue to take montelukast as in the period of reaching the control of symptoms of bronchial asthma, and during the exacerbation of the disease.

For elderly patients, patients with renal insufficiency, patients with mild or moderate liver function disorders, no special dose selection is required.

Montelukast can be added to treatment with bronchodilators and inhaled glucocorticosteroids (GCS).

A drug Montelukast is also produced in the form of chewable tablets 5 mg for the treatment of children aged 6 to 14 years.

Side effects:

From the nervous system: headache, dizziness, drowsiness, paresthesia / hypoesthesia. very rarely - cramps.

From the side of the psyche: agitation including aggressive behavior or hostility, anxiety, depression, disorientation, tremors, impaired attention, unusual vivid dreams, hallucinations, impaired memory, psychomotor activity (including irritability, anxiety), fatigue, somnambulism, suicidal ideation and suicidal behavior (suicidality ), insomnia.

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, indigestion, pancreatitis, dry mouth.

From the musculoskeletal system: arthralgia, myalgia, including muscle cramps.

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

From the cardiovascular system: cardiopalmus.

On the part of the respiratory system, the organon of the thorax and the mediastinum: nosebleeds, pulmonary eosinophilia.

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).

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

From the side of the blood and lymphatic system: increased tendency to bleeding, thrombocytopenia.

From the immune system: hypersensitivity reactions, including anaphylaxis, eosinophilic liver infiltration.

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

Other: edema, asthenia (weakness) / fatigue, pyrexia, thirst.

Generally montelukast well tolerated.Side effects are usually mild and. as a rule, do not require the cancellation of treatment.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Data on the symptoms of an overdose when taking montelukast by 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 1 week has not been revealed.

There are reports of acute overdose of montelukast in children (taking at least 1000 mg of the drug per day). Clinical and laboratory data indicate that the safety profile of Montelukast in children is consistent with the safety profile in adults and elderly patients. The most frequent adverse events were thirst, drowsiness, vomiting, psychomotor agitation, headache, mydriasis, hyperkinesia and abdominal pain.

Treatment is symptomatic.

There is no data on the possibility of removing montelukast by peritoneal dialysis or hemodialysis.

Interaction:

Montelukast can be prescribed together with other drugs traditionally used for the prevention and long-term treatment of bronchial asthma and / or allergic rhinitis.The recommended therapeutic dose of montelukast had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol / norethisterone 35/1), terfenadine, digoxin and warfarin.

AUC is reduced in persons who simultaneously receive phenobarbital (approximately 40%), however, correction of the dosage regimen of montelukast to such patients is not required.

In vitro studies found that montelukast inhibits isozyme ECM 2S8 cytochrome P450, but in the study of drug interactions in vivo montelukast and rosiglitazone (metabolized with isoenzyme CYP 2S8 cytochrome) received confirmation inhibition montelukast CYP 2S8-mediated metabolism of certain drugs, including paclitaxel, rosiglitazone, repaglinide.

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 the CYP isoenzyme ZA4, 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 adults patients for 22 weeks and up to 900 mg / day for patients taking the drug for about one pedal, no clinically significant adverse effects were observed). 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 significant drug interactions with other known inhibitors of CYP 2C8 (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.

Treatment with bronchodilators: montelukast can be added to the treatment of patients whose asthma is not controlled by the use of single bronchodilators. When the therapeutic effect (usually after the first dose) is achieved against the background of montelukast therapy, the dose of bronchodilators can be gradually reduced.

Inhaled glucocorticosteroids: Treatment with Montelukast provides an additional therapeutic effect to patients receiving treatment with inhaled glucocorticosteroids. When the stabilization of the patient is achieved, a reduction in the dose of glucocorticosteroids is possible. The dose of glucocorticosteroids should be reduced gradually, under the supervision of a doctor. In some patients, the intake of inhaled glucocorticosteroids can be completely abolished. It is not recommended to sharply replace therapy with inhaled glucocorticosteroids by the appointment of montelukast.

Special instructions:

The effectiveness of montelukast for oral administration with respect to the treatment of acute attacks of bronchial asthma is not established, therefore montelukast It is not recommended to prescribe for treatment of acute attacks of bronchial asthma. Patients should always have emergency medication to relieve asthma attacks (short-acting inhaled beta2-agonists).You should not stop taking montelukast during a period of exacerbation of bronchial asthma and the need to use emergency drugs to stop seizures.

Patients with a confirmed allergy to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during treatment with montelukast. because the montelukast, improving respiratory function in patients with allergic bronchial asthma, nevertheless, can not completely prevent the bronchoconstriction caused by their NSAIDs.

The dose applied simultaneously with the drug Montelukast Inhaled glucocorticosteroids can be gradually reduced under the supervision of a physician. However, a sharp replacement of glucocorticosteroids with the drug Montelukast to conduct it is impossible.

Reducing the dose of systemic glucocorticosteroids in patients receiving antiasthmatic drugs, including leukotriene receptor blockers, has been accompanied in rare cases by the appearance of eosinophilia, rash, impairment of pulmonary symptoms, cardiac complications and / or neuropathy, sometimes diagnosed as Chard-Strauss syndrome (systemic eosinophilic vasculitis).The causal relationship between the development of these undesirable events and therapy with leukotriene receptor antagonists has not been proven, nevertheless, care must be taken and appropriate clinical observation should be carried out with a reduction in the dose of systemic glucocorticosteroids in patients taking montelukast.

The drug contains lactose monohydrate, and it should not be taken to patients with rare hereditary diseases: galactose intolerance, lactase insufficiency or glucose-galactose malabsorption.

In patients receiving 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 / caregivers need to explain that in case of such symptoms it is necessary to inform the attending physician about it.

Effect on the ability to drive transp. cf. and fur:The data indicating that the administration of montelukast affects the ability to drive a car or moving mechanisms is not revealed.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, film-coated 10 mg.

Packaging:For 7 or 10 tablets per contour cell package (A1 / A1). By 2, 4 or 14 contour cellular packs No. 7 in a pack of cardboard with instructions for medical use of the drug. By 2, 3, 4, 9 or 14 contour mesh packages No. 10 in a pack of cardboard with instructions for medical use of the drug.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003903

Date of registration:17.10.2016

Expiration Date:17.10.2021

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

Sanico N.V. Belgium

Information update date: & nbsp02.06.2018

Illustrated instructions

Instructions

Montelukast (Montelukast)