Milukante (Montelukast) 10mg 28 chewable tablets — Made in Poland by Adamed — Free Delivery

Pharmacological properties

Pharmacodynamics. Cysteinyl leukotrienes (ltc4, ltd4, lte4) are potent pro-inflammatory eicosanoids that are released from a variety of cells, including mast cells and eosinophils. these important pro-asthmatic mediators bind to cysteinyl leukotriene receptors (cyslt), which are found in the human respiratory tract and are responsible for the bronchospasm response, sputum production, vascular permeability and an increase in the number of eosinophils. cyslts correlate with the pathophysiology of BA and allergic rhinitis. in allergic rhinitis, cysteinyl leukotrienes are released from nasal mucus after exposure to an allergen during the early or late phase of the reaction and are associated with symptoms of allergic rhinitis.

Montelukast is an active compound that binds with high affinity and selectivity to CysLT1 receptors. Montelukast significantly blocks airway cysteinyl leukotriene receptors, which is confirmed by its ability to inhibit bronchoconstriction in AD patients caused by inhalation of LTD4.

Montelukast, even at a dose of up to 5 mg, inhibits bronchoconstriction after inhalation of LTD4. Bronchodilation is noted within 2 hours after oral administration. The bronchodilation effect caused by the β-adrenergic receptor agonist is combined with the effect caused by montelukast. Treatment with montelukast inhibited the early and late phases of bronchoconstriction due to the effect on antigens. Treatment with montelukast significantly reduced the number of eosinophils in the airways (as measured in sputum). Also, montelukast reduces the number of eosinophils in adults and children aged 2-14 years in the peripheral blood and improves the clinical control of asthma.

In a study involving children aged 2 to 5 years, montelukast 4 mg reduced the severity of daytime (including coughing, wheezing, difficulty breathing, and limited activity) and nighttime symptoms, and also reduced the frequency of β-agonist use when necessary and urgent use of corticosteroids with worsening BA. In patients who used montelukast, a greater number of days without symptoms of asthma was recorded.

In a study involving children aged 2 to 5 years with mild asthma and episodic exacerbations, montelukast at a dose of 4 mg reduced the summer frequency of asthma exacerbations.

In a study involving children aged 6 months to 5 years with intermittent (but not persistent) asthma, there was no significant difference between patients treated with montelukast at a dose of 4 mg and those who received placebo regarding the number of episodes of asthma that pass in an asthma attack (defined as an episode of asthma, requiring an unscheduled visit to a doctor, emergency room, or hospital; or treatment with oral, IV, or IM corticosteroids).

In a study involving children aged 6 to 14 years, montelukast at a dose of 5 mg significantly improved respiratory function and reduced the frequency of use of β-agonists when needed.

In a study comparing the efficacy of montelukast and inhaled fluticasone for controlling asthma in children aged 6 to 14 years with persistent mild asthma, montelukast showed no less efficacy than fluticasone in increasing the number of days without the use of fast-acting emergency preparations.

A significant reduction in exercise-related bronchospasm has been demonstrated in a study in adults. This effect was observed over the 12-week study period. Reducing exercise-related bronchospasm has also been shown in a short study in children aged 6 to 14 years. The effect in both studies was demonstrated at the end of this period.

During studies involving adults, montelukast at a dose of 10 mg showed a significant improvement in the morning forced expiratory volume in 1 s (FEV1), the morning peak expiratory flow rate, and a significant decrease in the total use of β-agonists. The decrease in the severity of the day and night BA symptoms reported by the patient was significantly greater.

Pharmacokinetics. Absorption. Montelukast is rapidly and almost completely absorbed after oral administration. After taking 4 mg chewable tablets on an empty stomach in children aged 2–5 years, Cmax is reached 2 hours after ingestion. The Cmax is 66% higher and the Cmin is lower than in adults who took 10 mg tablets.

After taking on an empty stomach 5 mg chewable tablets by children aged 5-14 years, Cmax is reached 2 hours after ingestion. Bioavailability was 73% and decreased to 63% with regular food intake.

For 10 mg film-coated tablets taken on an empty stomach in adults, the average Cmax value is reached after 3 hours (Tmax). The average bioavailability is 64% with regular food intake. Average bioavailability and Cmax do not depend on normal food.

Indications

Milukante 4 mg

Children aged 2-5

As an additional treatment for asthma in patients aged 2 to 5 years with persistent mild to moderate asthma, which is insufficiently controlled by inhaled corticosteroids, as well as in case of insufficient clinical control of asthma with the help of short-acting β-adrenergic receptor agonists, used if necessary.

As an alternative method of treatment instead of low-dose inhaled corticosteroids for patients aged 2 to 5 years with persistent mild asthma, who have not had any recent serious attacks of asthma requiring oral corticosteroids, and who are unable to use inhaled corticosteroids (see APPLICATION).

Prevention of asthma in patients aged 2 years and older, in whom the dominant component of asthma is exercise-induced bronchospasm.

Reducing the severity of symptoms of seasonal and perennial allergic rhinitis.

Milukante 5 mg

Children aged 6 to 14

As an additional treatment for asthma in patients with persistent mild to moderate asthma, insufficiently controlled by inhaled corticosteroids, as well as in case of insufficient clinical control of asthma with the help of short-acting β-adrenergic receptor agonists, used if necessary.

As an alternative method of treatment instead of low-dose inhaled corticosteroids for patients with persistent mild asthma, who have not recently experienced serious attacks of asthma requiring oral corticosteroids, and who cannot use inhaled corticosteroids (see APPLICATION).

Prevention of asthma, the dominant component of which is exercise-induced bronchospasm.

Reducing the severity of symptoms of seasonal and perennial allergic rhinitis.

Milukante 10 mg

As an additional treatment for asthma in patients with persistent mild to moderate asthma, insufficiently controlled by inhaled corticosteroids, as well as in case of insufficient clinical control of asthma with the help of short-acting β-adrenergic receptor agonists, used if necessary. In AD patients taking Milukante, this preparation also reduces the severity of symptoms of seasonal allergic rhinitis.

Prevention of asthma, the dominant component of which is exercise-induced bronchospasm.

Reducing the severity of symptoms of seasonal and perennial allergic rhinitis.

The efficacy and safety of this dosage form has been demonstrated in clinical studies in which 10 mg film-coated tablets were used regardless of food.

Distribution. More than 99% of montelukast binds to blood plasma proteins. The equilibrium volume of distribution of montelukast averages 8–11 liters. In studies with labeled radioactive montelukast, the minimum penetration through the BBB was determined. In addition, the concentrations of the radioactive substance 24 hours after administration were minimal in all other tissues.

Metabolism. Montelukast is metabolized almost completely. In studies of therapeutic doses, it was impossible to determine the equilibrium concentration of montelukast metabolites in blood plasma in adults and children. In vitro studies using human liver microsomes, it was found that the cytochrome P450 3A4, 2A6 and 2C9 system is involved in the metabolism of montelukast. Based on further in vitro tests on human liver microsomes, therapeutic plasma concentrations of montelukast do not inhibit the cytochrome P450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6 system. The participation of metabolites in the therapeutic effect of montelukast is minimal.

Elimination. Plasma clearance of montelukast averages 45 ml / min in healthy adults.

After oral administration, about 86% of the labeled radioactive montelukast is excreted in the feces for 5 days and less than 0.2% in the urine. Since montelukast and its metabolites are almost completely eliminated in the bile, dose adjustment is not required for patients with impaired renal function.

Pharmacokinetics in different patient groups. For elderly patients, as well as for patients with mild to moderate hepatic insufficiency, dose adjustment is not required. No dose adjustment is necessary for patients with impaired renal function, since montelukast and its metabolites are almost completely eliminated in the bile. There are no data on the nature of the pharmacokinetics of montelukast in patients with severe hepatic impairment.

When taking montelukast in high doses (exceeding the therapeutic ones by 20–60 times), a decrease in the concentration of theophylline in the blood plasma was noted. When taken in therapeutic doses, this effect was not detected.

Application

Milukante 4 mg

The preparation must be used in children under adult supervision.

Patients with asthma and allergic rhinitis (seasonal and year-round) should take 1 chewable tablet (4 mg) once a day. To reduce the severity of symptoms of allergic rhinitis, the time of admission should be selected individually.

For BA treatment, the dose for children aged 2 to 5 years is 1 chewable tablet (4 mg) per day, in the evening. Milukante should be taken 1 hour before meals or 2 hours after meals. No dose adjustment is necessary for this age group. The preparation Milukante in the dosage form of chewable tablets (4 mg) is not recommended for children under 2 years of age.

General recommendations for the use of the preparation. The therapeutic effect of Milukant in controlling asthmatic manifestations was noted within 1 day. Patients should be advised to continue taking Milukante even if asthma is under control, as well as during periods of exacerbation of asthma.

It is not required to adjust the dose for patients with renal impairment, mild or moderate hepatic impairment. There is no data on dose adjustment for patients with severe hepatic impairment. Dosing for male and female patients is identical.

Milukante as an alternative treatment for low-dose inhaled corticosteroids in persistent mild asthma. Montelukast is not recommended for monotherapy in patients with moderate persistent asthma. The use of montelukast as an alternative to low-dose inhaled corticosteroids in children with persistent mild asthma can be considered only in those patients who have not recently had serious attacks of asthma requiring oral corticosteroids, or who cannot take inhaled corticosteroids. Mild persistent asthma is defined as asthma with symptoms more often than 1 time per week, but less often than 1 time per day, nocturnal symptoms more often than 2 times a month, but less often than 1 time per week, and normal lung function between episodes. If a satisfactory BA control is not achieved in the future (usually within 1 month), it is necessary to assess the need for additional or other anti-inflammatory preparations based on a step-by-step BA therapy system. It is necessary to periodically assess BA control in patients.

Prevention of asthma in patients aged 2 to 5 years in whom the main component of asthma is exercise-induced bronchospasm. Milukante is recommended for patients aged 2 to 5 years for the prevention of exercise-induced bronchospasm, which can be the main manifestation of persistent asthma, which requires the use of inhaled corticosteroids.

The patient's condition should be assessed 2–4 weeks after starting treatment with montelukast. If a satisfactory result of therapy is not achieved, a decision should be made on additional or alternative treatment.

Treatment with Milukante versus other treatments. In the case when treatment with Milukante is additional to therapy with inhaled corticosteroids, Milukante should not be abruptly administered instead of inhaled corticosteroids.

Milukante 5 mg

Patients with asthma and allergic rhinitis (seasonal and year-round) should take 1 chewable tablet (5 mg) once a day. To reduce the severity of symptoms of allergic rhinitis, the time of admission should be selected individually.

For BA treatment, the dose for children aged 6 to 14 years is 1 chewable tablet (5 mg) per day, in the evening. Milukante should be taken 1 hour before meals or 2 hours after meals. No dose adjustment is necessary for this age group.

General recommendations for the use of the preparation. The therapeutic effect of the preparation Milukant in controlling asthmatic manifestations was noted within 1 day. Patients should be advised to continue taking Milukante even if asthma is under control, as well as during periods of exacerbation of asthma.

It is not required to adjust the dose for patients with renal impairment, mild or moderate hepatic impairment. There is no dose adjustment data for patients with severe hepatic impairment. Dosing for male and female patients is identical.

Milukante as an alternative treatment for low-dose inhaled corticosteroids in persistent mild asthma. Montelukast is not recommended for monotherapy in patients with moderate persistent asthma. The use of montelukast as an alternative to low-dose inhaled corticosteroids in children with persistent mild asthma can be considered only for those patients who have not recently had a serious attack of asthma requiring oral corticosteroids, or who cannot take inhaled corticosteroids.

Mild persistent asthma is defined as asthma with symptoms more often than 1 time per week, but less often than 1 time per day, nocturnal symptoms more often than 2 times a month, but less often than 1 time per week, and normal lung function between episodes. If a satisfactory BA control is not achieved in the future (usually within 1 month), it is necessary to assess the need for additional or other anti-inflammatory preparations based on a step-by-step BA therapy system. It is necessary to periodically assess BA control in patients.

Treatment with Milukante versus other treatments. In the case when treatment with Milukante is additional to therapy with inhaled corticosteroids, Milukante should not be abruptly administered instead of inhaled corticosteroids.

Milukante 10 mg

The dose for patients (over the age of 15 years) with asthma or with asthma and concomitant seasonal allergic rhinitis is 10 mg (1 tablet) per day, in the evening. To reduce the severity of symptoms of allergic rhinitis, the time of admission should be selected individually.

No dose adjustment is required for patients with mild or moderate hepatic impairment. No dose adjustment data are available for patients with severe hepatic impairment. No dose adjustment is required for elderly patients.

General recommendations

The therapeutic effect of Milukant in terms of BA control parameters is observed within 1 day. The preparation can be used regardless of food intake. Patients should be advised to continue taking the preparation even if asthma is under control, as well as during periods of worsening asthma.

Milukante should not be used concurrently with other preparations that contain the same active ingredient - montelukast.

No dose adjustment is required for elderly patients. No dose adjustment is also required for patients with renal insufficiency, mild to moderate liver damage. There are no data on patients with severe liver damage. Dosing for male and female patients is identical.

Treatment with Milukante versus other BA treatments. Milukante can be added to the patient's existing course of treatment.

Inhaled corticosteroids. Treatment with Milukante can be used as an additional therapy for patients in whom inhaled corticosteroids, together with the necessary short-acting β-agonists, do not provide the necessary clinical control of asthma.

Do not abruptly replace inhaled corticosteroids with Milukante .

Contraindications

Hypersensitivity to the active substance or any auxiliary component.

Side effects

Milukante is well tolerated. in clinical trials, long-term treatment in different age groups demonstrates a consistent safety profile.

Infections and infestations: upper respiratory tract infections.

On the part of the circulatory and lymphatic systems: a tendency to increased bleeding.

From the immune system: hypersensitivity reactions, including anaphylaxis, eosinophilic liver infiltration.

From the side of the psyche: impaired attention, memory impairment, sleep disturbances, including nightmares, insomnia, somnambulism, irritability, anger, impatience, anxiety, agitation, including aggressive behavior or hostility, depression, tremors; very rarely - hallucinations, disorientation, suicidal thoughts and behavior (attempted suicide).

From the nervous system: dizziness and lethargy, drowsiness, paresthesia / hypesthesia, seizures, headache.

On the part of the cardiovascular system: palpitations.

On the part of the respiratory system, chest and mediastinal organs: nosebleeds, Churge-Strauss syndrome (CSS).

From the digestive system: diarrhea, dry mouth, dyspepsia, nausea, vomiting, abdominal pain.

From the hepatobiliary system: an increased level of serum transaminases (ALT, ASAT), hepatitis, including cholestatic, hepatocellular and mixed types, liver damage.

On the part of the kidneys and urinary tract: enuresis in children.

Skin and subcutaneous tissue disorders: angioedema, hematoma, urticaria, pruritus, rash, erythema nodosum, erythema multiforme.

From the musculoskeletal system and connective tissue: arthralgia, myalgia, including muscle cramps.

General disorders and condition of the injection site: fever, asthenia / increased fatigue, discomfort, edema, thirst.

Special instructions

Patients should be warned not to use Milukante for acute BA and should be kept ready with their usual first aid medications for these cases. if an acute attack develops, short-acting inhaled β-adrenergic receptor agonists should be used. patients should consult their physician as soon as possible if they need more inhalations of short-acting β-adrenergic agonists than usual.

Do not abruptly substitute montelukast for inhaled or oral corticosteroid therapy. There is no evidence that oral corticosteroid intake can be reduced while taking montelukast.

In rare cases, patients receiving anti-asthma preparations, including montelukast, may develop systemic eosinophilia, sometimes accompanied by clinical signs of vasculitis, the so-called Churg-Strauss syndrome, a condition that is treated with systemic corticosteroids. These cases are usually, but not always, associated with a reduction or withdrawal of oral corticosteroid therapy. It cannot be ruled out or established that leukotriene receptor antagonists may be associated with the development of Churg-Strauss syndrome. Therefore, doctors should be warned about the possibility of eosinophilia, vasculitic eruptions, increased severity of pulmonary symptoms, cardiac complications and / or neuropathy in patients. Patients who develop the aforementioned symptoms need to be reexamined, and their treatment regimen should be reviewed. Treatment with montelukast does not exclude the need to avoid taking acetylsalicylic acid and other NSAIDs in patients with aspirin asthma.

Milukante 4 and 5 mg chewable tablets contain aspartame, a source of phenylalanine. This can adversely affect people with phenylketonuria. Patients with phenylketonuria should take into account that 1 chewable tablet 4 mg contains phenylalanine in an amount equivalent to 0.674 mg / dose, and 1 chewable tablet 5 mg contains phenylalanine in an amount equivalent to 0.842 mg / dose.

Milukante 10 mg film-coated tablets contain lactose, so patients with rare hereditary diseases of galactose intolerance, lactose deficiency or glucose-galactose malabsorption should not take it.

During pregnancy and breastfeeding. Pregnancy. Animal studies have not found any harmful effects of montelukast on pregnancy or embryonic / fetal development.

The limited data from the available pregnancy databases do not suggest a causal relationship between montelukast and malformations (such as limb defects), which have rarely been reported in post-marketing studies worldwide. Most of these women were also taking other anti-asthma medications. The causal relationship between these cases and the use of montelukast has not been proven.

When prescribing Milukante to pregnant women, the benefit / risk ratio must be taken into account.

Lactation. Studies in rats have shown that montelukast passes into breast milk.

There is no data on the penetration of Milukante into the breast milk of women who are breastfeeding, therefore, the benefit / risk ratio must be taken into account when prescribing Milukante during breastfeeding.

Fertility In animal studies, montelukast did not affect fertility or reproductive function with systemic exposure, which exceeded the clinical systemic exposure by more than 24 times.

Children. Milukante , 4 mg chewable tablets, is intended for use in children aged 2–5 years. Milukante , 5 mg chewable tablets, is indicated for use in children aged 6-14 years. Milukante 10 mg is used in children over the age of 15 and adults.

The ability to influence the reaction rate when driving and working with other mechanisms. Usually Milukante  does not affect the ability to drive vehicles or work with other mechanisms, but very rarely drowsiness was noted in patients who took the preparation, therefore, while taking the preparation, you should refrain from driving or operating other mechanisms.

Interactions

Montelukast can be used concurrently with other preparations for the prevention and treatment of chronic BA. in preparation interaction studies, the recommended clinical dose of montelukast did not have a clinically important effect on the pharmacokinetics of the following preparations: theophylline, prednisolone, oral contraceptives (ethinylestradiol / norethindrone 35/1), terfenadine, digoxin and warfarin.

AUC values ​​for montelukast decreased by about 40% in individuals who were taking phenobarbital at the same time. Montelukast is metabolized by CYP 3A4, 2C8 and 2C9, therefore, precautions must be taken, especially in children, if it is administered concomitantly with CYP inducers 3A4, 2C8 and 2C9, such as phenytoin, phenobarbital and rifampicin.

In vitro studies have shown that montelukast is a potent inhibitor of CYP 2C8. However, data from clinical studies of preparation interactions between montelukast and rosiglitazone (a marker substrate representing preparations primarily metabolized by CYP 2C8) showed that montelukast is not inhibited by CYP 2C8 in vivo. Therefore, montelukast is not expected to significantly alter the metabolism of preparations metabolized by this enzyme (eg paclitaxel, rosiglitazone and repaglinide).

In vitro studies have shown that montelukast is a substrate for CYP 2C8 and, to a lesser extent, for 2C9 and 3A4. In a clinical study of preparation interactions involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9), gemfibrozil increased the systemic effect of montelukast by 4.4 times. Usually, dose adjustment of montelukast when used simultaneously with gemfibrozil or other powerful inhibitors of CYP 2C8 is not required, but in this case, the doctor should take into account the possibility of an increase in the severity of adverse reactions.

Based on in vitro studies, clinically significant preparation interactions with less potent inhibitors of CYP 2C8 (for example, trimethoprimoi) are not provided. The simultaneous use of montelukast with itraconazole, a potent inhibitor of CYP 3A4, did not significantly increase the systemic exposure of montelukast.

Overdose

There is no specific information regarding the treatment of montelukast overdose. in studies with ba montelukast was prescribed in doses up to 200 mg / day to adult patients for 22 weeks, and in short-term studies - up to 900 mg / day for about 1 week, clinically significant adverse reactions did not develop.

In the post-marketing period and clinical studies, an acute overdose of montelukast has been reported. These cases involved adults and children who took doses up to 1000 mg (about 61 mg / kg in a 42-month-old child). The clinical and laboratory studies obtained were consistent with the safety profile in adults and children.

In most reports of overdose cases, no adverse events have been identified. The most common manifestations of side effects were consistent with the safety profile of the preparation  and included abdominal pain, drowsiness, thirst, headache, vomiting, and psychomotor hyperactivity. Treatment is symptomatic. It is not known whether montelukast is excreted by peritoneal dialysis or hemodialysis.

Storage conditions

In original packaging.