Monler^® (Tablets) Instructions for Use

ATC Code

R03DC03 (Montelukast)

Active Substance

Montelukast (Rec.INN WHO registered)

Clinical-Pharmacological Group

Leukotriene receptor antagonist. Drug for the treatment of bronchial asthma and allergic rhinitis

Pharmacotherapeutic Group

Drugs for the treatment of obstructive airway diseases; other systemic agents for the treatment of obstructive airway diseases; leukotriene receptor antagonists

Pharmacological Action

Leukotriene receptor antagonist. Montelukast binds with high selectivity and chemical affinity to CysLT₁ receptors (instead of other pharmacologically important airway receptors, such as prostanoid, cholinergic, or β-adrenergic receptors).

Montelukast inhibits the physiological action of cysteinyl leukotrienes LTC₄, LTD₄, and LTE₄ by binding to CysLT₁ receptors without exerting an agonist effect on these receptors. Montelukast inhibits CysLT₁ receptors in the airway epithelium, thereby possessing the ability to inhibit bronchospasm induced by inhalation of LTD₄ in patients with bronchial asthma.

A dose of 5 mg is sufficient to block LTD₄-induced bronchospasm.

Montelukast causes bronchodilation within 2 hours after oral administration and may complement bronchodilation induced by beta₂-adrenergic agonists.

Pharmacokinetics

After oral administration, Montelukast is rapidly and almost completely absorbed from the gastrointestinal tract. In adults receiving doses of 5-10 mg, the C_max in plasma is reached in 2-3 hours. Oral bioavailability is 64-73%.

The plasma protein binding of montelukast is more than 99%. The V_d averages 8-11 L.

With a single daily dose of 10 mg, moderate accumulation (approximately 14%) of the active substance in plasma is observed.

Montelukast is extensively metabolized in the liver. At therapeutic doses, the concentrations of montelukast metabolites in plasma at steady state are undetectable in adults and children.

It is presumed that the isoenzymes CYP3A4 and CYP2C9 are involved in the metabolism of montelukast; at therapeutic concentrations, Montelukast does not inhibit the isoenzymes CYP3A4, 2C9, 1A2, 2A6, 2C19, and 2D6.

The T_1/2 of montelukast in young healthy adults ranges from 2.7 to 5.5 hours. The clearance of montelukast in healthy adults averages 45 ml/min. After oral administration of montelukast, 86% is excreted in the feces over 5 days and less than 0.2% in the urine, confirming that Montelukast and its metabolites are excreted almost exclusively via bile.

The pharmacokinetics of montelukast remain nearly linear following oral administration of doses greater than 50 mg.

Indications

Prophylaxis and long-term treatment of bronchial asthma, including: prevention of daytime and nighttime symptoms of the disease; treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid; prevention of exercise-induced bronchoconstriction.

Relief of daytime and nighttime symptoms of seasonal allergic rhinitis.

ICD codes

Dosage Regimen

Take orally, once daily in the evening.

For bronchial asthma prophylaxis and long-term treatment in adults and adolescents 15 years and older: administer one 10 mg tablet daily.

For pediatric patients 6 to 14 years old with asthma: administer one 5 mg chewable tablet daily.

For allergic rhinitis symptom relief in adults and adolescents 15 years and older: administer one 10 mg tablet daily.

For exercise-induced bronchoconstriction prevention in adults and adolescents 15 years and older: administer one 10 mg tablet at least 2 hours before exercise.

Do not take an additional dose within 24 hours for exercise protection.

For patients with both asthma and allergic rhinitis, take only one dose daily in the evening.

Continue therapy during asthma exacerbations and when using rescue medication (short-acting inhaled beta₂-agonists).

Do not abruptly substitute Montelukast for inhaled or oral corticosteroids.

Reduce concomitant inhaled corticosteroid doses gradually under medical supervision.

Dose adjustment is not required for elderly patients or those with renal impairment.

No dosage adjustment is recommended in mild to moderate hepatic impairment.

Take with or without food.

Adverse Reactions

Infections and infestations: very common – upper respiratory tract infections.

Blood and lymphatic system disorders: uncommon – increased bleeding tendency; frequency unknown – thrombocytopenia.

Immune system disorders: uncommon – hypersensitivity reactions, including anaphylaxis; very rare – eosinophilic infiltration of the liver.

Psychiatric disorders: uncommon – agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, dream abnormalities, insomnia, psychomotor hyperactivity (including irritability, restlessness, and tremor), somnambulism, tic; rare – attention disturbance, memory impairment; very rare – hallucinations, suicidal thoughts and behavior (suicidality).

Nervous system disorders: uncommon – headache, dizziness, drowsiness, paresthesia/hypoesthesia, seizures.

Cardiac disorders: rare – palpitations.

Respiratory, thoracic and mediastinal disorders: uncommon – epistaxis; very rare – pulmonary eosinophilia.

Gastrointestinal disorders: common – diarrhea, nausea, vomiting; uncommon – dyspepsia, dry mouth; frequency unknown – abdominal pain, pancreatitis.

Hepatobiliary disorders: common – increased ALT and AST; very rare – hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury).

Skin and subcutaneous tissue disorders: common – rash; uncommon – pruritus, urticaria, increased tendency to bruising; rare – angioedema; very rare – erythema nodosum, erythema multiforme.

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

Renal and urinary disorders: frequency unknown – enuresis in children.

General disorders and administration site conditions: common – pyrexia; uncommon – asthenia (weakness)/fatigue, edema, thirst; in patients with asthma, rare – development of Churg-Strauss syndrome.

Contraindications

Hypersensitivity to montelukast; pediatric age – depending on the dosage form.

Use in Pregnancy and Lactation

During pregnancy, Montelukast should be used only if the potential benefit to the mother justifies the potential risk to the fetus, only under medical supervision, and only at the lowest effective doses.

Cases of congenital limb defects in newborns have been reported in mothers who took Montelukast during pregnancy. Most of these women also took other medications for asthma during pregnancy. A causal relationship between montelukast use and the occurrence of congenital limb defects has not been established.

It is not known whether Montelukast is excreted in human milk. Montelukast should not be used during breastfeeding.

Pediatric Use

Can be used in children according to indications, in age-appropriate recommended doses and dosage forms. It is necessary to strictly follow the instructions for montelukast preparations regarding contraindications for the use of specific dosage forms in children of different ages.

Geriatric Use

Can be used in elderly patients according to indications in recommended doses and regimens.

Special Precautions

The efficacy of oral montelukast for the treatment of acute asthma attacks has not been established. Therefore, oral Montelukast is not recommended for the treatment of acute asthma attacks. Patients should be instructed to always have rescue medication for acute asthma attacks (short-acting inhaled beta₂-agonists) with them.

Treatment with montelukast should not be abruptly discontinued during an asthma exacerbation or when the need for rescue medication (short-acting inhaled beta₂-agonists) arises.

Patients with confirmed allergy to acetylsalicylic acid and other NSAIDs should not take these medications during treatment with montelukast, because although Montelukast improves respiratory function in patients with allergic asthma, it cannot completely prevent NSAID-induced bronchoconstriction in these patients.

The dose of inhaled corticosteroids used concomitantly with montelukast can be gradually reduced under medical supervision; however, montelukast should not be abruptly substituted for inhaled or oral corticosteroids.

Effect on ability to drive and operate machinery

Some patients experienced drowsiness and dizziness while taking montelukast. If these symptoms occur, patients are advised not to drive vehicles or engage in other activities requiring concentration and rapid psychomotor reactions.

Drug Interactions

Concomitant use with phenobarbital decreased the AUC of montelukast by approximately 40% (no adjustment of the montelukast regimen is required).

In vitro studies have shown that Montelukast inhibits the CYP2C8 isoenzyme; however, an in vivo drug interaction study of montelukast and rosiglitazone (metabolized by CYP2C8) did not confirm inhibition of CYP2C8 by montelukast. Therefore, no clinically significant effect of montelukast on CYP2C8-mediated metabolism of drugs such as paclitaxel, rosiglitazone, and repaglinide is anticipated in clinical practice.

In vitro studies indicate that Montelukast is a substrate of CYP2C8, 2C9, and 3A4 isoenzymes. Data from a clinical drug interaction study with montelukast and gemfibrozil (an inhibitor of both CYP2C8 and 2C9 isoenzymes) show that gemfibrozil increased the systemic exposure of montelukast by 4.4-fold.

Coadministration of itraconazole, a potent CYP3A4 inhibitor, together with gemfibrozil and montelukast did not result in any additional increase in the systemic exposure of montelukast.

Montelukast is a rational addition to monotherapy with bronchodilators when the latter do not provide adequate control of asthma. Once a therapeutic effect is achieved with montelukast, a gradual reduction in the dose of bronchodilators may be initiated.

Use of montelukast provides additional therapeutic effect in patients receiving inhaled corticosteroids. Once the condition is stabilized, a gradual reduction of the corticosteroid dose may be initiated under medical supervision. In some cases, complete discontinuation of inhaled corticosteroids may be possible; however, abrupt replacement of inhaled corticosteroids with Montelukast is not recommended.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.