Ektalust^® (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

Anti-inflammatory anti-bronchoconstrictor agent – leukotriene receptor antagonist

Pharmacological Action

Montelukast has the ability to inhibit bronchospasm induced by inhalation of LTD4 at very low doses. Bronchodilation is observed within 2 hours after oral administration of the drug. The bronchodilation effect induced by beta-adrenergic agonists is complemented by the action of montelukast. Montelukast inhibits the early and late phases of bronchospasm induced by antigen administration. Montelukast reduces the number of eosinophils in the peripheral blood, in the airways (in sputum) of adult patients and children and improves control over the course of bronchial asthma. Montelukast significantly improves morning forced expiratory volume (FEV1) in 1 second, maximum expiratory flow rate (PEFR) and significantly reduces the need for beta-adrenergic agonists.

Montelukast enhances the effect of inhaled corticosteroids and significantly reduces bronchospasm induced by physical exertion. In patients with aspirin-sensitive bronchial asthma taking concomitant inhaled or oral corticosteroids, treatment with montelukast leads to a significant improvement in the control of bronchial asthma symptoms. In addition, there is evidence of some anti-inflammatory effect of montelukast.

Pharmacokinetics

Absorption and Bioavailability

Montelukast is rapidly and almost completely absorbed after oral administration. The bioavailability for 5 mg chewable tablets when taken orally is 73% and decreases to 63% when taken with food. After administration of 4 mg and 5 mg chewable tablets, the time to reach C_max(T_max) is 2 hours. After administration of 4 mg chewable tablets on an empty stomach by children aged 2 to 5 years, T_max is 2 hours. The mean C_max(66%) is higher, while C_min in children is lower than in adults taking 10 mg.

Distribution

Montelukast is more than 99% bound to plasma proteins. The V_d of montelukast averages 8-11 L.

Preclinical studies have revealed minimal penetration of the drug through the blood-brain barrier. The concentration of montelukast 24 hours after drug administration was minimal in all body tissues.

Metabolism

Montelukast is actively metabolized in the liver. When using therapeutic doses, the concentration of montelukast metabolites in plasma at steady state in adults and children is not determined. It is assumed that cytochrome P450 CYP isoenzymes (3A4 and 2C9) are involved in the metabolism of montelukast, while at therapeutic concentrations Montelukast does not inhibit the cytochrome P450 CYP isoenzymes: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

Excretion

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

The pharmacokinetics of montelukast remain almost linear after oral administration of doses above 50 mg. No differences in pharmacokinetics are observed when montelukast is taken in the morning and evening.

Pharmacokinetics in different patient groups

Gender

The pharmacokinetics of montelukast in men and women are similar.

Age

When montelukast is taken once daily at a dose of 10 mg, the pharmacokinetic profile and bioavailability are similar in elderly and young patients.

Ethnicity

No clinically significant differences in pharmacokinetic effects have been identified in patients of different races.

Renal impairment

Since Montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast in patients with renal impairment have not been evaluated. Dose adjustment of the drug for this group of patients is not required.

Hepatic impairment

In patients with mild to moderate hepatic impairment and clinical manifestations of liver cirrhosis, a slowdown in the metabolism of montelukast was noted, accompanied by an increase in the AUC area by approximately 41% after a single dose of the drug at a dose of 10 mg. The elimination of montelukast in these patients is somewhat increased compared to healthy people (mean T_1/2 – 7.4 hours). Dose adjustment of montelukast for patients with mild to moderate hepatic impairment is not required. There are no data on the pharmacokinetics of montelukast in severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Indications

• Long-term treatment and prevention of bronchial asthma, including prevention of daytime and nighttime symptoms of the disease;
• Treatment of aspirin-induced asthma;
• Prevention of bronchospasm induced by physical exertion;
• Relief of daytime and nighttime symptoms of persistent and seasonal allergic rhinitis.

ICD codes

Dosage Regimen

Tablets

Ektalust^® is taken orally, the tablet should be chewed 1 hour before meals or 2 hours after meals, once a day. For the treatment of bronchial asthma, the drug should be taken in the evening. When treating allergic rhinitis, the drug can be taken at any time of day at the patient’s discretion.

For adults aged 15 years and older, it is recommended to use other dosage forms of montelukast (for example, film-coated tablets, 10 mg).

For children from 2 to 5 years, 1 chewable tablet at a dose of 4 mg once a day, before bedtime. Dose selection for this age group is not required.

For children from 6 to 14 years, 1 chewable tablet at a dose of 5 mg once a day, before bedtime. Dose selection for this age group is not required.

General recommendations

The therapeutic effect of the drug Ektalust^® on symptoms reflecting the course of bronchial asthma appears within the first day. The patient should continue taking the drug Ektalust^® both during the controlled course of bronchial asthma and during the exacerbation of the disease.

For elderly patients, patients with renal impairment, patients with mild and/or moderate hepatic impairment, dose adjustment is not required.

Prescription of the drug Ektalust^® simultaneously with other types of asthma treatment

Ektalust^® can be added to the patient’s treatment with bronchodilators and inhaled corticosteroids (see section “Drug Interactions”).

Adverse Reactions

In general, the drug Ektalust^® is well tolerated. Side effects are usually mild and, as a rule, do not require discontinuation of treatment. The overall frequency of side effects reported with the use of montelukast is comparable to that of placebo.

Disorders of the blood and lymphatic system increased tendency to bleeding.

Disorders of the immune system: hypersensitivity reactions, including anaphylaxis, eosinophilic infiltration of the liver (very rare – 0.01%).

Psychiatric disorders: agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, abnormal dreams, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thoughts and behavior (suicidality), tremor.

Disorders of the nervous system: headache, dizziness, drowsiness, paresthesia/hypoesthesia, hyperkinesia, seizures (very rare – <0.01%).

Cardiac disorders palpitations.

Disorders of the respiratory system, thoracic and mediastinal organs epistaxis, upper respiratory tract infections, pharyngitis, cough, sinusitis, rhinorrhea.

Ear and labyrinth disorders otitis (including media).

Gastrointestinal disorders: diarrhea, dyspepsia, nausea, vomiting, pancreatitis, abdominal pain, dry mouth.

Disorders of the liver and biliary tract: increased activity of liver transaminases in the blood ALT, AST, hepatitis (including cholestatic, hepatocellular and mixed liver lesions) (very rare – <0.01%).

Disorders of the skin and subcutaneous tissues: angioedema, tendency to form hematomas, erythema nodosum, erythema multiforme, itching, rash, urticaria.

Disorders of the musculoskeletal and connective tissue: arthralgia, myalgia, including muscle spasms.

General disorders and administration site conditions: asthenia (weakness)/fatigue, edema, pyrexia, thirst. In rare cases, patients with bronchial asthma have developed Churg-Strauss syndrome.

Contraindications

• Hypersensitivity to any of the components of the drug;
• Phenylketonuria;
• Children under 2 years of age (for the 4 mg dosage);
• Children under 6 years of age (for the 5 mg dosage).

Use in Pregnancy and Lactation

Ektalust^® should be used during pregnancy and breastfeeding only if the expected benefit to the mother outweighs the potential risk to the fetus or child.

Use in Hepatic Impairment

For patients with mild and/or moderate hepatic impairment, dose adjustment is not required.

Use in Renal Impairment

For patients with renal impairment, dose adjustment is not required.

Pediatric Use

The use of the drug is prohibited for children under 2 years of age (for the 4 mg dosage) and for children under 6 years of age (for the 5 mg dosage). For adults aged 15 years and older, it is recommended to use other dosage forms of montelukast.

Geriatric Use

For elderly patients, dose adjustment is not required.

Special Precautions

The effectiveness of the oral drug Ektalust^® for the treatment of acute attacks of bronchial asthma has not been established, therefore the drug Ektalust^® in tablets is not recommended for the treatment of acute attacks of bronchial asthma. The drug Ektalust^® should not replace inhaled or oral corticosteroids.

There are no data indicating the possibility of reducing the dose of oral corticosteroids with concomitant use of the drug Ektalust^®. In rare cases, in patients taking drugs for the treatment of bronchial asthma, including the drug Ektalust^®, systemic eosinophilia may occur, sometimes accompanied by clinical manifestations of vasculitis and Churg-Strauss syndrome. This condition is usually treated with systemic corticosteroids. Such cases are usually, but not always, associated with a reduction in dose or withdrawal of oral corticosteroids. It is impossible to either exclude or confirm the likelihood that taking leukotriene receptor antagonists may be associated with the occurrence of Churg-Strauss syndrome. Doctors should be aware of the possibility of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications and/or neuropathy in patients. Patients who develop the above symptoms should be re-examined and their treatment regimen should be reconsidered.

The drug is not used to relieve attacks of bronchial asthma as an emergency drug, but its administration should not be discontinued during an exacerbation.

Patients with confirmed allergy to acetylsalicylic acid and other NSAIDs should not take these drugs during treatment with the drug Ektalust^®, since it, while improving respiratory function in patients with allergic bronchial asthma, nevertheless cannot completely prevent bronchoconstriction caused by NSAIDs.

Patients with phenylketonuria should be informed that 1 chewable tablet of 4 mg contains on average 0.8 mg of aspartame, and 1 chewable tablet of 5 mg contains on average 1 mg of aspartame.

Effect on ability to drive vehicles and operate machinery

No data have been identified indicating that taking the drug Ektalust^® affects the ability to drive vehicles or operate machinery. However, when using the drug, there are such side effects as dizziness and drowsiness. In view of this, caution should be exercised when driving vehicles and performing work that requires quick psychomotor reactions.

Overdose

Symptoms no data on symptoms of overdose when taking the drug by patients with bronchial asthma at a dose exceeding 200 mg/day for 22 weeks and at a dose of 900 mg/day for 1 week have been identified.

There are reports of acute overdose of montelukast in children (taking at least 150 mg of the drug per day). The most common adverse events were thirst, drowsiness, mydriasis, hyperkinesia and abdominal pain.

Treatment symptomatic. There is no information on specific treatment for overdose of the drug Ektalust^®.

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

Drug Interactions

Ektalust^® can be prescribed together with other drugs traditionally used for the prevention and long-term treatment of bronchial asthma. The recommended clinical dose of montelukast did not have a clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.

AUC decreases in individuals simultaneously receiving phenobarbital (by approximately 40%). However, adjustment of the dosage regimen of the drug Ektalust^® is not required for such patients.

Since Montelukast is metabolized by the CYP3A4 isoenzyme, caution should be exercised, especially in children, when prescribing montelukast concomitantly with drugs that induce the CYP3A4 isoenzyme, such as phenytoin, phenobarbital and rifampicin.

In vitro studies have shown that Montelukast is a potential inhibitor of the CYP2C8 isoenzyme, however, data from clinical drug-drug interaction studies including Montelukast and rosiglitazone (a preliminary substrate of a representative of medical drugs primarily metabolized by the CYP2C8 isoenzyme) showed that montelukast doses do not inhibit the CYP2C8 isoenzyme in vivo. Therefore, Montelukast does not have a noticeable effect on the metabolism of drugs metabolized by this enzyme (for example, paclitaxel, rosiglitazone and repaglinide).

When taking high doses of montelukast (20 and 60 times the recommended dose for adults), a decrease in the plasma concentration of theophylline is observed. This effect is not observed when taking the drug in recommended doses – 10 mg/day.

Bronchodilators: Ektalust^® can be added to the treatment of patients whose asthma is not controlled by the use of bronchodilators alone. When a therapeutic effect is achieved (usually after the first dose) during therapy with the drug Ektalust^®, the dose of bronchodilators can be gradually reduced.

Inhaled corticosteroids: treatment with the drug Ektalust^® provides an additional therapeutic effect for patients receiving treatment with inhaled corticosteroids. When the patient’s condition stabilizes, it is possible to reduce the dose of corticosteroids. The dose of corticosteroids should be reduced gradually, under medical supervision. In some patients, inhaled corticosteroids may be completely discontinued. It is not recommended to abruptly replace therapy with inhaled corticosteroids with the prescription of the drug Ektalust^®.

Storage Conditions

The drug should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.