Montelar, 5 mg 28 pcs.

Montelar is a bronchodilator.

Pharmacodynamics

Blocker of cysteinyl leukotriene receptors of airway epithelium CysLT1 (LT C4, D4 and E4 – mediators of chronic persistent inflammation that maintain bronchial hyperresponsiveness in bronchial asthma). Prevents excessive formation of secretion in the bronchi, edema of the airway mucosa. Reduces the severity of bronchial asthma and the frequency of asthmatic attacks. It is highly effective when taken orally.

The bronchodilator effect develops within 1 day and lasts for a long time.

Pharmacokinetics

Absorption. Montelukast is rapidly and almost completely absorbed after oral administration from the GI tract. Bioavailability for oral tablets 5 mg is 73%; for film-coated tablets 10 mg – 64%. After taking chewable 4 and 5 mg tablets, T_max is 2 hours; for film-coated 10 mg tablets, 3 hours.

Distribution and metabolism. Montelukast binds to plasma proteins by more than 99%. The average V_d of montelukast averages 8-11 liters.

Montelukast is actively metabolized in the liver. With therapeutic doses, plasma concentrations of montelukast metabolites are not detected in equilibrium in adults and children.

It is assumed that cytochrome P450 isoenzymes (3A4 and 2C9) are involved in the metabolism of montelukast, and at therapeutic concentrations montelukast does not inhibit CYP isoenzymes: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

Elimination. Plasma clearance is 45 ml/min. After oral administration, montelukast is almost completely excreted through the intestine (about 86%) and less than 0.2% by the kidneys.

The T_1/2 of montelukast in young healthy adults is 2.7 to 5.5 hours.

Pharmacokinetics in special cases

The pharmacokinetics of montelukast in women and men is similar.

There is no need to adjust the dosing regimen for elderly patients and patients with mild to moderate hepatic impairment.

Because montelukast and its metabolites are excreted from the body through the intestine, no dose adjustment is necessary for patients with renal impairment.

Indications

Active ingredient

Composition

1 tablet contains:

Montelukast sodium – 5.2 MG, which corresponds to the content of montelukast – 5 mg;

Auxiliary substances:

Mannitol – 194.9 mg,

microcrystalline cellulose – 66 mg,

croscarmellose sodium – 15 mg,

Hyprolose (EXF type) – 9 mg,

cherry flavoring – 2.4 mg (contains 0.07% Allura red AC (E129) colorant),

aspartame – 1.2 mg,

cherry flavoring – 0.6 mg,

iron (III) oxide red dye – 0.45 mg,

magnesium stearate – 5.25 mg.

How to take, the dosage

Ingestion, once daily, before going to bed.

If the drug is taken in combination with food, Montelukast should be taken 1 hour before or 2 hours after the meal.

The drug is indicated for children under adult supervision.

For children 2 to 5 years of age, one chewable tablet at a dose of 4 mg once daily, before bedtime (use of 4 mg montelukast chewable tablets is not recommended for children under 2 years of age); 6 to 14 years old – one chewable tablet in dose of 5 mg once daily, before sleep (use of chewable tablets Montelar® 5 mg is not recommended before the age of 6 years). The therapeutic effect of Montelukast develops during the 1st day of taking the drug. The patient should continue to take montelukast both during the period of achieving control of bronchial asthma symptoms and during periods of exacerbation of bronchial asthma.

For prophylaxis in children with exercise-induced bronchospasm: 2 to 5 years – 1 chewable tablet at a dose of 4 mg once daily, before bedtime for 2-4 weeks; 6 to 14 years – 1 chewable tablet at a dose of 5 mg once daily, before bedtime for 2-4 weeks. If there is no satisfactory effect, additional or alternative therapy should be prescribed.

Other dosage forms of montelukast (e.g., film-coated tablets, 10 mg) are recommended for the treatment of patients older than 15 years and adults.

In patients with renal impairment and mild to moderate hepatic impairment, and depending on gender, no special dose adjustment is necessary.

Interaction

Montelukast can be administered together with other drugs traditionally used for prevention and long-term treatment of bronchial asthma, such as bronchodilators and inhaled GCS. The recommended therapeutic dose of montelukast had no clinically significant effect on pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethinsterone 35/1), terfenadine, digoxin and warfarin.

The AUC value decreases in persons concomitantly receiving phenobarbital (approximately 40%), but the dosing regimen of montelukast does not need to be adjusted in these patients. In vitro studies have shown that montelukast is a potential inhibitor of CYP2C8 isoenzyme of cytochrome P450 system, but data from clinical studies of “drug-drug interaction” including montelukast and rosiglitazone (a preliminary substrate representative of medicines primarily metabolized by CYP2C8 isoenzyme) showed that montelukast doses do not inhibit CYP2C8 isoenzyme in vivo. Consequently, montelukast has no significant effect on the metabolism of medications metabolized by this enzyme (e.g., paclitaxel, rosiglitazone and repaglinide).

In vitro studies have shown that montelukast is a substrate of CYP2C8, CYP2C9 and CYP3A4. Data from a clinical study of drug interaction between montelukast and gemfibrozil (an inhibitor of both CYP2C8 and CYP2C9) demonstrate that gemfibrozil increases the systemic effect of montelukast by 4.4-fold.

The co-administration of intraconazole, a strong CYP3A4 inhibitor, together with gemfibrozil and montelukast did not result in an additional increase in the systemic effect of montelukast. The effect of gemfibrozil on the systemic effects of montelukast cannot be considered clinically significant based on safety data when used at doses greater than the approved dose of 10 mg for adult patients (e.g., 200 mg/day for adult patients for 22 weeks and up to 900 mg/day for patients taking the drug for approximately one week with no clinically significant adverse effects observed).

Hence, no dose adjustment of montelukast is required when coadministered with gemfibrozil.

According to the results of in vitro studies, no clinically significant drug interactions are expected with other known CYP2C8 inhibitors (e.g. with trimethoprim). In addition, co-administration of montelukast with intraconazole alone did not significantly increase the systemic effect of montelukast.

Combination treatment with bronchodilators

Montelur® is a reasonable adjunct to monotherapy with bronchodilators if the latter do not adequately control bronchial asthma. Once therapeutic benefit has been achieved (usually after the first dose) from Montelar® treatment, a gradual reduction in the dose of bronchodilators may be initiated.

Combined treatment with inhaled GCS

The treatment with Montelar® provides additional therapeutic benefit to patients using inhaled GCS. Once the patient’s condition has stabilized, a gradual decrease in the dose of GCS under a physician’s supervision may begin. In some cases complete withdrawal of inhaled GCS is acceptable, however, abrupt replacement of inhaled GCS by Montelar® is not recommended.

Because montelukast is metabolized by the CYP3A4 isoenzyme, caution should be exercised, especially in children over 15 years of age, if montelukast is concomitantly prescribed with drugs that induce the CYP3A4 isoenzyme, such as phenytoin, phenobarbital and rifampicin.

Special Instructions

Continue use of montelukast is recommended even after significant improvement has been achieved. Montelukast is not recommended for the treatment of acute attacks of bronchial asthma. In the acute course of bronchial asthma, patients should use emergency medicines to control attacks (inhaled β2-adrenomimetics of short action).

Decreasing the systemic dose of GCS in patients receiving anti-asthmatic agents, including leukotriene receptor antagonists, was accompanied in rare cases by the development of Churg-Strauss syndrome (systemic eosinophilic vasculitis), manifested as eosinophilia, vascular rash, increased severity of pulmonary symptoms and, if not appropriately treated, cardiac complications and/or neuropathy. Although a causal relationship between these adverse events and therapy with leukotriene receptor antagonists has not been established, caution and appropriate clinical monitoring should be exercised when reducing the systemic dose of GCS in patients taking montelukast.

The dose of GCS used with montelukast should be decreased gradually under medical supervision. Abrupt replacement of inhaled or oral GCS therapy with montelukast is not recommended. Patients with confirmed allergies to acetylsalicylic acid and other NSAIDs should avoid contact with these medications during treatment with montelukast because montelukast, while improving respiratory function in patients with allergic bronchial asthma, does not prevent NSAID-induced bronchoconstriction.

When reducing the systemic dose of GCS in patients taking montelukast, caution should be exercised and appropriate clinical monitoring should be performed. No age-related differences in the efficacy and safety profile of montelukast have been identified. Patients with phenylketonuria should be informed that 1 4 mg chewable tablet contains at least 0.96 mg aspartame and 1 5 mg chewable tablet contains at least 1.2 mg aspartame.

The chewable tablets contain the dye Charming red (Allura red), which may cause allergic reactions.

Special precautions for disposal of unused medication. No special precautions are necessary when destroying unused Montelar® medicine.

Impact on the ability to drive vehicles and engage in other activities requiring concentration and rapid psychomotor reactions. There are no data indicating that the use of montelukast affects the ability to drive or operate moving mechanisms. However, drowsiness and dizziness have been reported, therefore in case of appearance of these signs patients are not recommended both to drive vehicles and to engage in other activities requiring concentration and quick psychomotor reactions.

Contraindications

Side effects

CNS disorders: often – headache.

Gastrointestinal disorders: often – pain in the abdomen.

Postmarketing observations

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

Hemostasis: increased tendency to bleeding, including nasal bleeding, bruising.

The immune system: infrequent hypersensitivity reactions, including anaphylaxis; rare – angioedema; very rare – eosinophilic liver infiltration.

Skin and subcutaneous tissue disorders: rash, infrequent tendency to form hematomas, urticaria, pruritus; very rare erythema nodosum, erythema multiforme.

CNS disorders: infrequent – headache, dizziness, somnolence, paresthesia/hypesthesia, seizures, hyperkinesia.

Mental disorders: infrequent – sleep disorders (including nightmares), somnambulism, insomnia, irritability, anxiety, agitation (including aggressive behavior or hostility), depression; rarely – tremor; very rare – hallucinations, disorientation, suicidal thoughts and behavior.

Systemic system disorders: rarely – feeling of palpitations.

Blood and lymphatic system disorders: rare – increased tendency to bleeding.

Gastrointestinal disorders: frequently – abdominal pain, diarrhea, nausea, vomiting, pancreatitis; infrequently – dry mouth, dyspepsia.

Hepatic and biliary tract disorders: common – increased activity of liver transaminases (ALT, ACT); very rarely – cholestatic hepatitis, hepatocyte damage, usually with concomitant drug therapy or with existing liver pathology (various forms of hepatitis).

Musculoskeletal and connective tissue disorders: infrequent – arthralgia, myalgia, including muscle cramps.

Respiratory system disorders: infrequent – nasal bleeding; very rare – Churg-Strauss syndrome.

Sensory system disorders: otitis media (including middle).

Others: infrequent – asthenia/fatigue, malaise, edema, hyperthermia, thirst, flu-like syndrome, pyrexia.

Overdose

Symptoms: thirst, drowsiness, vomiting, mydriasis, hyperkinesias, psychomotor agitation, headache and abdominal pain are the most common.

Treatment: carrying out symptomatic therapy. There are no data on the possibility of excretion of montelukast by peritoneal dialysis or hemodialysis.

Pregnancy use

The use of Montelar® in pregnancy and lactation is possible only if the expected benefits to the mother exceed the potential risk to the fetus or child.

Similarities