Montevell (Tablets) Instructions for Use

ATC Code

R03DC03 (Montelukast)

Active Substance

Montelukast (Rec.INN registered by WHO)

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 actions of the cysteinyl leukotrienes LTC₄, LTD₄, and LTE₄ by binding to CysLT₁ receptors without exerting any agonist activity on these receptors. Montelukast inhibits CysLT₁ receptors in the airway epithelium, thereby possessing the ability to inhibit bronchospasm induced by inhaled LTD₄ in patients with asthma.

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

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

Pharmacokinetics

After oral administration, Montelukast is rapidly and almost completely absorbed from the gastrointestinal tract. In adults following administration of a 5-10 mg dose, the peak plasma concentration (C_max) is achieved within 2-3 hours. The oral bioavailability is 64-73%.

The plasma protein binding of montelukast is more than 99%. The mean volume of distribution (V_d) is 8-11 L.

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

Montelukast is extensively metabolized in the liver. At therapeutic doses, the plasma concentrations of montelukast metabolites are undetectable at steady state 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 CYP3A4, 2C9, 1A2, 2A6, 2C19, and 2D6 isoenzymes.

The half-life (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 an oral dose of montelukast, 86% is excreted in the feces over 5 days and less than 0.2% is excreted in the urine, confirming that Montelukast and its metabolites are excreted almost exclusively via the bile.

The pharmacokinetics of montelukast remain approximately 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 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 asthhma prophylaxis and treatment in adults and adolescents 15 years and older: administer one 10 mg tablet daily.

For asthhma prophylaxis and treatment in pediatric patients 6 to 14 years old: administer one 5 mg chewable tablet daily.

For allergic rhinitis, administer daily at a time convenient for the patient; timing can be individualized.

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

Do not take an additional dose within 24 hours for exercise-induced bronchoconstriction.

Patients with both asthma and allergic rhinitis should take only one tablet daily.

Montelukast may be added to existing therapy with bronchodilators and/or inhaled corticosteroids.

Do not abruptly substitute montelukast for inhaled or oral corticosteroids.

Reduce the dose of concomitant inhaled corticosteroids gradually under medical supervision.

This medication is not for the treatment of acute asthma attacks.

Always have rescue medication available for acute symptoms.

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 – hepatic eosinophilic infiltration.

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 bruise; 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/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 justifies the potential risk to the fetus, only under medical supervision, and only at the lowest effective dose.

Cases of limb defects in newborns have been reported following exposure to Montelukast during pregnancy. Most of these women also took other medications for asthma during pregnancy. A causal relationship between montelukast exposure and the occurrence of 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 the 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 the 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 advised to always have rescue medication for acute asthma attacks (short-acting inhaled beta₂-agonists) available.

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

Patients with known aspirin hypersensitivity should continue to avoid aspirin or other NSAIDs during montelukast treatment. While Montelukast improves respiratory function in patients with allergic asthma, it may not completely prevent NSAID-induced bronchoconstriction in these patients.

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

Effects on ability to drive and operate machinery

Drowsiness and dizziness have been reported in some patients taking montelukast. Patients experiencing these symptoms should be cautioned against driving vehicles or operating machinery, or engaging in activities requiring concentration and rapid psychomotor reactions.

Drug Interactions

Concomitant administration with phenobarbital decreased the AUC of montelukast by approximately 40% (no dosage adjustment for montelukast is recommended).

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

In vitro studies indicate that Montelukast is a substrate for CYP2C8, 2C9, and 3A4. Data from a clinical drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP2C8 and CYP2C9) demonstrate that gemfibrozil increases the systemic exposure of montelukast by 4.4-fold.

Coadministration of itraconazole, a potent CYP3A4 inhibitor, with gemfibrozil and montelukast did not further increase the systemic exposure of montelukast.

Montelukast is a rational addition to monotherapy with bronchodilators when they do not provide adequate control of asthma. Once a clinical response to montelukast is evident, a gradual reduction in the dose of bronchodilators may be attempted.

Montelukast provides additional clinical benefit to patients receiving inhaled corticosteroids. Once clinical stability is achieved, a gradual reduction of the corticosteroid dose may be undertaken under medical supervision. In some cases, complete discontinuation of inhaled corticosteroids may be possible; however, abrupt substitution of Montelukast for inhaled corticosteroids 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

Over-the-Counter

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.