Montelukast-Vertex, 10 mg 30 pcs

Pharmacotherapeutic group

An anti-inflammatory antibronchoconstrictor agent – leukotriene receptor blocker.

The ATC code: R03DC03

Pharmacological properties

Pharmacodynamics

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are strong inflammatory mediators – eicosanoids that are released by various cells, including mast cells and eosinophils. These important proasthmatic mediators bind to cysteinyl-leukotriene receptors.

Cysteinyl-leukotriene receptors type 1 (CysLT1 receptors) are present in the human airways (including bronchial smooth muscle cells, macrophages) and other proinflammatory 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 counts.

In allergic rhinitis, after allergen exposure, cysteinyl-leukotrienes are released from pro-inflammatory nasal mucosal cells during the early and late phases of the allergic reaction, which manifests as symptoms of allergic rhinitis.

In an intranasal test with cysteinyl-leukotrienes, increased nasal airway resistance and symptoms of nasal obstruction have been demonstrated.

Montelukast is a highly active oral medication that significantly improves inflammatory scores in bronchial asthma. According to biochemical and pharmacological analysis, montelukast binds with high affinity and selectivity to CysLT1 receptors without interacting with other pharmacologically important receptors in the airways (such as prostaglandin, cholinergic or β-adrenergic receptors).

Montelukast inhibits the physiological action of cysteinyl leukotrienes LTC4, LTD4, LTE4 by binding to CysLT1 receptors without having a stimulatory effect on these receptors.

Montelukast inhibits CysLT1 receptors in the airways, as evidenced by its ability to block the development of bronchospasm in response to inhalation of LTD4 in patients with bronchial asthma. The dose of 5 mg is sufficient to stop LTD4-induced bronchospasm.

Montelukast induces bronchodilatation within two hours after oral administration and may complement bronchodilatation induced by β2-adrenomimetics.

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

Pharmacokinetics

Intake

Montelukast is quickly and almost completely absorbed after oral administration. In adults, when film-coated tablets 10 mg are taken on an empty stomach, the maximum concentration (Cmax) is reached after 3 hours (Tmax). Average bioavailability when taken orally is 64%. Food intake has no effect on Cmax in plasma and bioavailability of montelukast.

Distribution

Montelukast binds to plasma proteins by more than 99%. The volume of distribution of montelukast in the state of equilibrium concentration is on average 8-11 liters. Studies with radioactively labeled montelukast in 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 studies of therapeutic doses in adults and children, plasma concentrations of metabolites of montelukast in equilibrium are undetectable.

In vitro studies using human liver microsomes have shown that cytochrome P450 isoenzymes are involved in the metabolism of montelukast: 3A4, 2A6 and 2C9. According to the results of in vitro studies in human liver microsomes, montelukast at therapeutic concentration in plasma does not inhibit cytochrome P450 isoenzymes: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

The plasma clearance of montelukast in healthy adults is on average 45 ml/min. After ingestion of radioactively labeled montelukast, 86% of its amount is excreted through the intestine within 5 days and less than 0.2% by the kidneys, confirming that montelukast and its metabolites are excreted almost exclusively with bile.

The half-life of montelukast in young healthy adults is 2.7 to 5.5 hours. The pharmacokinetics of montelukast remain almost linear when oral doses over 50 mg are taken. When taking montelukast in the morning and evening hours no differences in pharmacokinetics are observed. When taking 10 mg of montelukast once daily a moderate (about 14%) cumulation of the active substance in blood plasma is observed.

Particularities of pharmacokinetics in different groups of patients

Particularities of pharmacokinetics of montelukast in women and men are similar.

Elderly patients

In a single oral administration of 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in elderly and younger patients. The plasma elimination half-life of montelukast is somewhat longer in elderly patients. There is no need to adjust the dose of the drug in elderly patients.

Race

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

Patients with hepatic impairment

Patients with hepatic impairment. In patients with mild to moderate hepatic impairment and clinical manifestations of liver cirrhosis, a delay in the metabolism of montelukast was noted, accompanied by an increase in the area under the pharmacokinetic concentration-time curve (AUC) of approximately 41% after a single dose of montelukast 10 mg.

The excretion of montelukast is slightly increased in these patients compared to healthy volunteers (mean half-life of 7.4 hours). There is no need to change the dose of montelukast for patients with mild to moderate hepatic impairment. There are no data on the nature of the pharmacokinetics of montelukast in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Patients with renal impairment

As montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast in patients with renal impairment have not been evaluated. There is no need to adjust the dose of the drug for this group of patients.

Indications

Active ingredient

Composition

How to take, the dosage

One time a day regardless of meals. For treatment of bronchial asthma the drug should be taken in the evening. In 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 one tablet of Montelukast once a day in the evening.

Adults and adolescents 15 years of age and older

One film-coated tablet (10 mg) daily.

General recommendations

The therapeutic effect of montelukast on indicators reflecting the course of bronchial asthma develops within the first day. The patient should continue to take the drug both during the period of achieving control of bronchial asthma symptoms and during exacerbation of bronchial asthma.

Particular patient groups

There is no special dose adjustment required for elderly patients, patients with renal impairment, and patients with mild to moderate hepatic impairment, or depending on gender.

Prescribing montelukast concomitantly with other bronchial asthma treatment

Montelukast can be added to patient treatment with bronchodilators and inhaled glucocorticosteroids (see “Interaction with other medications”).

Interaction

Montelukast in recommended doses does not affect the pharmacokinetics of prednisone, theophylline, prednisolone, terfenadine, combined oral contraceptives, digoxin, warfarin. Also, montelukast has no effect (but no clinical studies) on thyroid hormones, decongestants, benzodiazepines, and nonsteroidal anti-inflammatory drugs.

In vitro data, montelukast can inhibit a cytochrome P450 2C8 system isoenzyme, but in vivo this has not been confirmed. Therefore, it can be assumed that montelukast will not affect the pharmacokinetics of drugs that are metabolized with the participation of this enzyme (rosiglitazone, paclitaxel, repaglinide).

Contraindications

– hypersensitivity to Montelukast or any other component of the drug;

– age less than 15 years (for the given dosage of the drug);

Lactase deficiency, lactose intolerance, and glucose-galactose malabsorption

Side effects

Gastrointestinal system:Nausea, dyspepsia, vomiting, abdominal pain, diarrhea, impaired liver function, jaundice and hepatitis (including fulminant), increased liver transaminases, cholestatic, hepatocellular and mixed forms of hepatitis, pancreatitis.

Musculoskeletal system:myalgia, arthralgia, muscle cramps.

Allergic reactions:angioneurotic edema, anaphylaxis, rash, hypersensitivity reactions, urticaria, pruritus, eosinophilic liver infiltrates, erythema nodosa, erythema multiforme.

Others: tendency to form subcutaneous hemorrhages, increased bleeding, nasal bleeding, palpitations, flu-like syndrome, edema, cough, pharyngitis, sinusitis, thrombocytopenia, upper respiratory infections, palpitations, pyrexia, Cerj-Strauss syndrome.

Overdose

In case of overdose with montelukastom drowsiness, thirst, vomiting, hyperkinesias, mydriasis, psychomotor agitation, abdominal pain, headache develop.

Symptomatic treatment is necessary.

Pregnancy use

Similarities