Montlesir tablets p / o 10 + 5mg, No. 30

Treatment of symptoms of perennial (persistent) and seasonal (intermittent) allergic rhinitis.

Inside.

Adults and children over 15 years old, 1 single dose 1 time / day.

The duration of treatment depends on the duration of the symptoms.

Active ingredients: levocetirizine dihydrochloride 5 mg

montelukast sodium 10.4 mg, which corresponds to the content of montelukast 10 mg *

Excipients:

lactose monohydrate (Tablettose 100) - 63.5 mg,

microcrystalline cellulose (Avicel PH 102) - 30.2 mg,

colloidal silicon dioxide - 0.3 mg,

magnesium stearate - 1 mg. **

Excipients:

lactose monohydrate (Pharmatose 200M) - 89.3 mg,

microcrystalline cellulose (Avicel PH 101) - 83.2 mg,

dye iron oxide yellow (iron oxide yellow) - 0.1 mg,

croscarmellose sodium - 13 mg,

hyprolose (hydroxypropyl cellulose) - 3 mg,

magnesium stearate - 1 mg.

The composition of the film shell:

Opadry yellow (Opadry yellow 13B52204) - 6 mg (hypromellose 6cP (HPMC 2910) - 3.75 mg, titanium dioxide 1.4556 mg, macrogol-400 - 0.375 mg, dye iron oxide yellow (iron oxide yellow) - 0.357 mg, polysorbate-80 - 0.06 mg, dye iron oxide red (iron oxide red) - 0.0024 mg).

Hypersensitivity to montelukast, levocetirizine (including piperazine derivatives),

end stage renal failure (CC <10 ml / min);

children under 15 years of age;

pregnancy,

period of breastfeeding.

Carefully:

Chronic renal failure (correction of the dosage regimen is required);

old age (a decrease in glomerular filtration is possible);

patients with spinal cord injury, prostatic hyperplasia, as well as in the presence of other predisposing factors to urinary retention, since levocetirizine may increase the risk of urinary retention;

with simultaneous use with alcohol.

Composition and form of release:

Film-coated tablets of yellow or brownish-yellow color, round, biconvex, smooth on both sides; in cross section, the core of two layers - one layer from white to almost white, the second layer is light yellow.

Active ingredients: levocetirizine dihydrochloride 5 mg

montelukast sodium 10.4 mg, which corresponds to the content of montelukast 10 mg *

Excipients:

lactose monohydrate (Tablettose 100) - 63.5 mg,

microcrystalline cellulose (Avicel PH 102) - 30.2 mg,

colloidal silicon dioxide - 0.3 mg,

magnesium stearate - 1 mg. **

Excipients:

lactose monohydrate (Pharmatose 200M) - 89.3 mg,

microcrystalline cellulose (Avicel PH 101) - 83.2 mg,

dye iron oxide yellow (iron oxide yellow) - 0.1 mg,

croscarmellose sodium - 13 mg,

hyprolose (hydroxypropyl cellulose) - 3 mg,

magnesium stearate - 1 mg.

The composition of the film shell:

Opadry yellow (Opadry yellow 13B52204) - 6 mg (hypromellose 6cP (HPMC 2910) - 3.75 mg, titanium dioxide 1.4556 mg, macrogol-400 - 0.375 mg, dye iron oxide yellow (iron oxide yellow) - 0.357 mg, polysorbate-80 - 0.06 mg, dye iron oxide red (iron oxide red) - 0.0024 mg).

Pharmachologic effect:

Combined antiallergic agent.

It is a combination of montelukast (a leukotriene receptor blocker) and levocetirizine (an H1-histamine receptor blocker).

Montelukast selectively inhibits CysLT receptors of cysteinyl leukotrienes of the respiratory tract epithelium.

Cysteinyl leukotriene receptors type 1 (CysLT receptors) are present in the human respiratory tract, incl. in bronchial smooth muscle cells, macrophages and other pro-inflammatory cells (including eosinophils and some myeloid stem cells).

Cysteinyl leukotrienes (LTC4, LTD4, LTE4) belong to the class of eicosanoids formed from arachidonic acid and are inflammatory mediators formed in various cells of the body, incl. in mast cells and eosinophils.

Cysteinyl leukotrienes correlate with the pathophysiology of bronchial asthma and allergic rhinitis.

In allergic rhinitis, after exposure to an allergen, cysteinyl leukotrienes are released from anti-inflammatory cells of the nasal mucosa during the early and late phases of an allergic reaction, which is manifested by symptoms of allergic rhinitis.

An intranasal test with cysteinyl leukotrienes showed an increase in the symptoms of nasal obstruction.

Montelukast binds with high affinity and selectivity to CysLT1 receptors, reduces the number of eosinophils in the peripheral blood, in the respiratory tract.

Levocetirizine - blocker of histamine H1-receptors, R-enantiomer of cetirizine; a competitive histamine antagonist; the affinity for histamine H1 receptors is 2 times higher than that of cetirizine.

Levocetirizine affects the histamine-dependent stage of allergic reactions; reduces the migration of eosinophils, reduces vascular permeability, limits the release of inflammatory mediators and cytokines (VCAM-1 and others).

Levocetirizine prevents the development and facilitates the course of allergic reactions, has an antiexudative, antipruritic effect; practically does not have anticholinergic and antiserotonin effects.

In therapeutic doses, it practically does not have a sedative effect.

The action begins 12 minutes after taking a single dose in 50% of patients, after 1 hour - in 95% and lasts for 24 hours.

Pharmacokinetics:

Montelukast

Montelukast is rapidly and almost completely absorbed after oral administration.

Regular food intake does not affect the bioavailability and Cmax of montelukast.

Plasma protein binding of montelukast is more than 99%. Vd averages 8-11 liters.

Montelukast is extensively metabolized in the liver.

When used in therapeutic doses, the concentrations of montelukast metabolites in plasma in an equilibrium state in adults and children are not determined.

It is assumed that the isoenzymes CYP3A4 and CYP2C9 are involved in the metabolic process of montelukast, while at therapeutic concentrations montelukast does not inhibit isoenzymes CYP3A4, CYP2C9, CYP1A2, CYP2A6, CYP2C19 and CYP2D6.

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

After oral administration of montelukast, 86% of the dose taken is excreted through the intestines within 5 days and less than 0.2% - by the kidneys, which confirms that montelukast and its metabolites are excreted almost exclusively in the bile. T1 / 2 in healthy adults ranges from 2.7 to 5.5 hours.

Pharmacokinetics:

montelukast remains virtually linear when taken orally in doses over 50 mg.

When taking montelukast in the morning and evening hours, there are no differences in pharmacokinetics.

When taken 1 time / day in montelukast therapy in the dosage form of 10 mg film-coated tablets, a moderate (about 14%) accumulation of the active substance in the plasma is observed.

Levocetirizine

Levocetirizine is rapidly and completely absorbed from the gastrointestinal tract when taken orally; food intake does not affect the completeness of absorption, but reduces its rate.

Bioavailability reaches 100%.

The time to reach Cmax in blood plasma is 0.9 h, Cmax is 270 ng / ml, Css is reached after 2 days.

Levocetirizine is 90% bound to blood plasma proteins. Vd - 0.4 l / kg.

Less than 14% of the levocetirizine dose is metabolized in the human body. the estimated differences in the pharmacokinetic profile of levocetirizine due to genetic polymorphism or concomitant administration of enzyme inhibitors are insignificant.

Metabolic transformations include oxidation of the aromatic ring, N- and O-dealkylation, and conjugation with taurine.

The dealkylation process is mainly carried out with the participation of the isoenzyme CYP3A4, while the oxidation of the aromatic ring occurs with the help of many and / or unidentified CYP isoforms.

Levocetirizine, when taken orally at a dose of 5 mg and / or when Cmax in blood plasma is exceeded, does not affect the activity of isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4.

Due to the limited metabolism and the lack of metabolic inhibitory activity, the interaction of levocetirizine at the metabolic level with other substances is unlikely. T1 / 2 of levocetirizine in adults is 7.9 ± 1.9 hours.

The average observed total clearance is 0.63 ml / min / kg.

It is completely excreted from the body within 95 hours. About 85.4% of the taken dose of the drug is excreted by the kidneys, about 12.9% through the intestines.

In renal failure (CC less than 40 ml / min), clearance decreases (in patients on hemodialysis - by 80%, which requires a change in the corresponding dosage regimen), T1 / 2 - lengthens.

Less than 10% is removed during a standard 4-hour hemodialysis procedure.

In patients with mild to moderate hepatic insufficiency and clinical manifestations of liver cirrhosis, a slowdown in the metabolism of montelukast was noted, accompanied by an increase in AUC by approximately 41% after a single dose of 10 mg of montelukast. T1 / 2 of montelukast in patients with hepatic insufficiency increases slightly compared with healthy volunteers (mean T1 / 2 - 7.4 hours).

In patients with renal insufficiency with CC less than 40 ml / min, the clearance of levocetirizine decreases.

In patients on hemodialysis, the total clearance is reduced by 80%, which requires a change in the dosage regimen.

Less than 10% is removed during a standard 4-hour hemodialysis procedure.

In children aged 6 to 11 years with a body weight of 20 to 40 kg, when taken orally once 5 mg of levocetirizine, the Cmax and AUC values ??are approximately 2 times higher than those in healthy adults.

Taking levocetirizine at a dose of 1.25 mg in children aged 6 months to 5 years leads to a plasma concentration corresponding to that in adults when taking 5 mg 1 time / day.

Indications:

Treatment of symptoms of perennial (persistent) and seasonal (intermittent) allergic rhinitis.

Contraindications:

Hypersensitivity to montelukast, levocetirizine (including piperazine derivatives),

end stage renal failure (CC <10 ml / min);

children under 15 years of age;

pregnancy,

period of breastfeeding.

Carefully:

Chronic renal failure (correction of the dosage regimen is required);

old age (a decrease in glomerular filtration is possible);

patients with spinal cord injury, prostatic hyperplasia, as well as in the presence of other predisposing factors to urinary retention, since levocetirizine may increase the risk of urinary retention;

with simultaneous use with alcohol.

Methods of administration and dosage:

Inside.

Adults and children over 15 years old, 1 single dose 1 time / day.

The duration of treatment depends on the duration of the symptoms.

Pregnancy and lactation:

Use during pregnancy and breastfeeding is contraindicated.

Storage conditions:

In a dark place at a temperature not exceeding 25 ? C.

Keep out of the reach of children.

Expiration date: 2 years.

Do not use after the expiration date printed on the package.