Singular, 5 mg 14 pcs

Pharmacodynamics

Montelukast inhibits cysteinyl leukotriene receptors of the airway epithelium, thus having simultaneously the ability to inhibit bronchospasm caused by inhaled cysteinyl leukotriene LTD4 in patients with bronchial asthma. A dose of 5 mg is sufficient to stop LTD4-induced bronchospasm. The use of montelukast in doses greater than 10 mg per day, taken once, does not increase the effectiveness of the drug.

Montelukast causes bronchodilation within 2 hours after oral administration; and may supplement bronchodilation induced by β2 -adrenomimetics.

Pharmacokinetics

Intake
Montelukast is rapidly and almost completely absorbed after oral administration. Normal food intake has no effect on the bioavailability and maximum plasma concentration (Cmax) of coated tablets and chewable tablets. Cmax is reached after 3 hours in adults when taking coated tablets 10 mg on an empty stomach. Bioavailability in per oral administration is 64%.
Cmax is reached in 2 hours in adults when taking chewable tablets 5 mg on an empty stomach. Bioavailability is 73%.

Distribution

Montelukast binds to plasma proteins by more than 99%. The volume of distribution of montelukast averages 8-11 liters.

Metabolism

Montelukast is actively metabolized in the liver. With therapeutic doses, plasma concentrations of montelukast metabolites are not determined in equilibrium in adults and children.
It is assumed that cytochrome P450 CYP isoenzymes (3A4 and 2C9) are involved in the metabolism of montelukast, and at therapeutic concentrations, montelukast is not inhibited by cytochrome P450 CYP isoenzymes: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

The clearance of montelukast in healthy adults is on average 45 ml/min. After oral administration of montelukast, 86% of it is excreted in the feces within 5 days and less than 0.2% in the urine, confirming that montelukast and its metabolites are excreted almost exclusively with the 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 once daily coated tablets 10 mg a moderate (about 14%) cumulation of the active substance in plasma is observed.

Particular pharmacokinetics in different groups of patients

Particular pharmacokinetics of montelukast in women and men are similar.

Elderly patients
When taken orally once daily in 10 mg film-coated tablets, pharmacokinetic profile and bioavailability are similar in elderly and younger patients.

Hepatic failure
In patients with mild to moderate hepatic failure and clinical manifestations of hepatic cirrhosis, a slowing of montelukast metabolism with an increase of approximately 41% of the area under the pharmacokinetic concentration-time curve (AUC) after a single dosing of 10 mg has been noted.

The excretion of montelukast is slightly increased in these patients compared to healthy subjects (median 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).

Race
No differences in clinically significant pharmacokinetic effects were found in patients of different races.

Renal Impairment
Because 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

Prevention and long-term treatment of bronchial asthma in adults and children from 6 years, including prevention of daytime and nighttime symptoms of the disease, treatment of aspirin-sensitive patients with bronchial asthma and prevention of exercise-induced bronchospasm.

Active ingredient

Composition

How to take, the dosage

Interaction

SINGULAR may be administered together with other drugs traditionally used for the prevention and long-term treatment of bronchial asthma. The recommended clinical dose of montelukast had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.

The AUC decreases in persons receiving phenobarbital concomitantly (approximately 40%), but dosing regimen adjustment is not required in these patients.

Treatment with bronchodilators: SINGULAR may be added to the treatment of patients in whom bronchial asthma is not controlled with bronchodilators alone. When a therapeutic effect is achieved (usually after the first dose) with SINGULAR therapy, the dose of bronchodilators can be gradually reduced.

Inhaled glucocorticosteroids: Treatment with SINGULAR provides additional therapeutic effect in patients treated with inhaled glucocorticosteroids. A reduction in the dose of glucocorticosteroids is possible when the patient’s condition reaches stabilization. The dose of glucocorticosteroids should be reduced gradually, under medical supervision. In some patients, inhaled glucocorticosteroids may be discontinued completely. Abrupt replacement of inhaled glucocorticosteroid therapy by prescription of SINGULAR is not recommended.

Special Instructions

SINGULAR tablets are not recommended for the treatment of acute attacks of bronchial asthma. In the acute course of bronchial asthma patients should be prescribed medication for asthma relief and asthma attack prevention.

The dose of inhaled glucocorticosteroids used concomitantly with SINGULAR may be gradually reduced under medical supervision. Inhaled or oral glucocorticosteroids should not be abruptly replaced with SINGULAR.

Decreasing the systemic dose of glucocorticosteroids in patients receiving anti-asthmatic agents, including leukotriene receptor blockers, has been accompanied in rare cases by the occurrence of one or more of the following phenomena eosinophilia, vascular rash, worsening of pulmonary symptoms, cardiac complications, and/or neuropathy, sometimes diagnosed as Churg-Strauss syndrome-systemic eosinophilic vasculitis.

While 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 glucocorticosteroids in patients taking SINGULAR.

Application in elderly patients

There are no age-related differences in the efficacy and safety profiles of SINGULAR.

Contraindications

Hypersensitivity to any of the ingredients of the drug Singular, children under 6 years of age.

Side effects

In general, SINGULAR is well tolerated. Side effects are usually mild and usually do not require treatment withdrawal.

The overall incidence of side effects reported with SINGULAR is comparable to that of placebo:

Hypersensitivity reactions (including anaphylaxis, angioedema, rash, pruritus, urticaria, and very rarely eosinophilic liver infiltrates);

Heuritis nodosa, unusual vivid dreams;

Hallucinations; drowsiness;

Irritability;

Agitation, including aggressive behavior;

Fatigue;

Suicidal thoughts and suicidal behavior (suicidality);

Insomnia;

Paresthesia/hypoesthesia and very rarely seizures;

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Nausea, vomiting, diarrhea, abdominal pain;

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Headache;

Arthralgia;

Myalgia;

Muscular cramps;

Tendency to increase bleeding, formation of subcutaneous hemorrhages;

Heart palpitations;

Swelling.

Overdose

There have been no reports of overdose symptoms in patients with bronchial asthma taking SINGULAR at a dose greater than 200 mg/day for 22 weeks and at a dose of 900 mg/day for 1 week.

There have been reports of acute overdose of montelukast in children (taking at least 150 mg of the drug per day). Clinical and laboratory data suggest that the safety profile of SINGULAR in children is consistent with the safety profile in adult and elderly patients. The most frequent adverse events were thirst, somnolence, mydriasis, hyperkinesias and abdominal pain.

The treatment is symptomatic.

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

Pregnancy use

SINGULAR should be used during pregnancy and lactation only if the expected benefit to the mother outweighs the potential risk to the fetus or child.

Similarities