Montlezir pills 5mg+10mg, 30pcs

Composition

Per tablet:

Core

1 layer:

Active ingredient:  levocetirizine dihydrochloride 5.0 mg;

Auxiliary substances:  lactose monohydrate (Lactose 100) 63.5 mg, microcrystalline cellulose (Avicel PH 102) 30.2 mg, colloidal silicon dioxide 0.3 mg, magnesium stearate 1.0 mg;

2 layer:

Active ingredient:  montelukast sodium 10.4 mg, equivalent to montelukast 10.0 mg;

Excipients: lactose monohydrate (Farmatosa 200 M) 89.3 mg, microcrystalline cellulose (Avicel PH 101) 83.2 mg, iron oxide yellow dye (iron oxide yellow) 0.1 mg, croscarmellose sodium 13.0 mg, hyprolose (hydroxypropylcellulose) 3.0 mg, magnesium stearate 1.0 mg;

Film shell

Opadray yellow (Opadray yellow 13 In 52204) 6.0 mg (hypromellose 6 sR (NRMS 2910) 3.75 mg, titanium dioxide 1.4556 mg, macrogol-400 0.375 mg, iron oxide yellow dye (iron oxide yellow) 0.357 mg, polysorbate-80 0.060 mg, iron oxide red dye (iron oxide red) 0.0024 mg).

Pharmacological action

Pharmacotherapy group

Leukotriene receptor blocker+H1-Histamine receptor blocker

Pharmacodynamics :

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

Montelukast selectively inhibits CysLT receptors of cysteinyl leukotrienes in the respiratory tract epithelium. Cysteinyl leukotriene type 1 receptors (CysLT receptors) are present in the human respiratory tract, including 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, including 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 the 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 to CysLT1 receptors with high affinity and selectivity and reduces the number of eosinophils in the peripheral blood in the respiratory tract.

Levocetirizine is an R-enantiomer of cetirizine; a competitive histamine antagonist; blocks H1-histamine receptors with an affinity 2 times higher than that of cetirizine. Levocetirizine has an effect on the histamine-dependent stage of allergic reactions; reduces the migration of eosinophils reduces vascular permeability restricts the release of inflammatory mediators and cytokines (VCAM-1 and others).

Levocetirizine prevents the development and eases the course of allergic reactions has an antiexudative antipruritic effect; practically does not have an anticholinergic and antiserotonin effect. In therapeutic doses, it has practically no sedative effect.

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

Pharmacokinetics:

Absorption rate

Montelukast is rapidly and almost completely absorbed after oral use. Regular food intake does not affect the bioavailability and maximum plasma concentration (Cmax) of montelukast. In adults, when taking montelukast on an empty stomach in the form of film-coated tablets at a dosage of 10 mg, Cmax is reached in 3 hours. Oral bioavailability is 64%.

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%. Time to reach the maximum concentration in blood plasma (Cmax) – 09 hours maximum concentration in blood plasma (Cmax) – 270 ng / ml equilibrium concentration is reached after 2 days.

Distribution

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

Levocetirizine is 90% bound to plasma proteins. The volume of distribution is 04 l/kg.

Metabolism

Montelukast is actively metabolized in the liver. When using therapeutic doses, plasma concentrations of montelukast metabolites at steady state in adults and children are not determined.

It is assumed that cytochrome P 450 CYP isoenzymes (3 A 4 and 2 C 9) are involved in the metabolism of montelukast, while at therapeutic concentrations montelukast does not inhibit the cytochrome P 450 CYP isoenzymes: 3 A 4 2 C 9 1 A 2 2 A 6 2 C 19 and 2D6.

In humans, less than 14% of the levocetirizine dose is metabolized, as the estimated differences in the pharmacokinetic profile of levocetirizine due to genetic polymorphism or simultaneous use of enzyme inhibitors are insignificant.

Metabolic transformations consist in the oxidation of the aromatic ring by N – and O-dealkylation and conjugation with taurine. The dealkylation process is mainly carried out with the help of the CYP3A4 isoenzyme, 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 exceeding the maximum concentrations in blood plasma does not affect the activity of CYP isoenzymes 1 A 2 2 C 9 2 C 19 2D6 2 E 1 3 A 4. Due to the limited metabolism and lack of metabolic inhibitory activity, the interaction of levocetirizine at the metabolic level with other substances is unlikely.

Deduction

The clearance of montelukast is on average 45 ml/min in healthy adults. After oral use of montelukast,86% of the dose is excreted by the intestine within 5 days and less than 02% by the kidneys, which confirms that montelukast and its metabolites are excreted almost exclusively in the bile. The elimination half-life in healthy adults is 27 to 55 hours.

The pharmacokinetics of montelukast remain almost linear when taking oral doses of more than 50 mg. When taking montelukast in the morning and evening hours, there are no differences in pharmacokinetics. When taking montelukast once a day in the dosage form of film-coated tablets 10 mg, moderate (about 14%) accumulation of the Active ingredient in plasma is observed.

The half-life of levocetirizine (T 1/2) in adults is 79 ± 19 hours. The average observed total clearance was 063 ml / min / kg. Completely eliminated from the body within 95 hours. About 854% of the drug dose is excreted by the kidneys, and about 129% is excreted through the intestines.

In patients with renal insufficiency (creatinine clearance less than 40 ml / min), clearance decreases (in patients on hemodialysis – by 80%, which requires a change in the appropriate dosage regimen), the half – life (T 1/2) is prolonged. Less than 10% is removed during a standard 4-hour hemodialysis procedure.

Features of montelukast pharmacokinetics in different groups of patients

The

pharmacokinetics of montelukast are similar in women and men.

Elderly patients

When taken orally once a day film-coated tablets containing 10 mg of montelukast, the pharmacokinetic profile and bioavailability are similar in the elderly and young patients.

Data on the pharmacokinetics of levocetirizine are limited. When repeated use of 30 mg of levocetirizine once a day for 6 days in elderly patients, the total clearance was approximately 33% lower than that in younger adult patients. It has been shown that the distribution of cetirizine racemate depends more on renal function than on age so in elderly patients the dose of the drug should be adjusted depending on renal function.

Liver failure

In patients with mild to moderate hepatic insufficiency and clinical manifestations of cirrhosis, a slowdown in montelukast metabolism was observed, accompanied by an increase in the area under the pharmacokinetic curve “concentration-time” (AUC) by approximately 41% after a single dose of 10 mg of montelukast.

The elimination period of montelukast in patients with hepatic insufficiency is slightly increased compared to healthy volunteers (the average half-life is 74 hours). No dose adjustment of montelukast is required in patients with mild to moderate hepatic insufficiency. There are no data on the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale).

Kidney failure

Since montelukast and its metabolites are not excreted in the urine, the pharmacokinetics of montelukast in patients with renal insufficiency have not been evaluated.

In patients with renal insufficiency, when creatinine clearance is less than 40 ml/min, the clearance of levocetirizine decreases. In patients undergoing hemodialysis, 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.

Children

In children aged 6 to 11 years with a body weight of 20 to 40 kg with a single oral dose of 5 mg of levocetirizine, the Cmax and area under the concentration-time curve (AUC) are approximately twice as high as in healthy adults. Taking levocetirizine at a dose of 125 mg in children aged 6 months to 5 years leads to a plasma concentration corresponding to that in adults when taking 5 mg of the drug once a day.

Race

There were no clinically significant differences in pharmacokinetic parameters in patients of different racial and ethnic groups.

Indications

Treatment of symptoms of year-round (persistent) and seasonal (intermittent) allergic rhinitis.

Use during pregnancy and lactation

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy have not been conducted.

The use of the drug during pregnancy is contraindicated.

There are no data on the excretion of montelukast in human breast milk.

Levocetirizine is excreted in breast milk. Therefore, if it is necessary to use the drug during lactation, it is recommended to stop breastfeeding.

Contraindications

Hypersensitivity to montelukast levocetirizine (including piperazine derivatives) and other components of the drug;

Lactase deficiency lactose intolerance glucose-galactose malabsorption;

End-stage renal failure (creatinine clearance below 10 ml / min);

Children under 15 years of age (due to limited data on safety and efficacy);

Pregnancy and breast-feeding period.

With caution:

Chronic renal failure (dosage adjustment is required); elderly (glomerular filtration rate may decrease); patients with spinal cord injury, prostatic hyperplasia, and other predisposing factors to urinary retention since levocetirizine may increase the risk of urinary retention; when used concomitantly with alcohol.

Side effects

The adverse events listed below are graded according to the following frequency: very common (≥ 1/10) common (≥ 1/100 to < 1/10) uncommon (≥ 1/1000 to < 1/100) rare (≥ 1/10000 to < 1/1000) very rare (

Montelukast

Disorders of the blood and lymphatic system: frequency unknown – increased tendency to bleeding thrombocytopenia.

Immune system disorders: rarely – hypersensitivity reaction including anaphylaxis very rarely-eosinophilic liver infiltration.

Mental disorders: frequency unknown-agitation including aggressive behavior or hostility anxiety depression disorientation pathological dreams hallucinations insomnia irritability restlessness somnambulism suicidal thoughts and behavior (suicidality) tremor attention and memory disorders.

Nervous system disorders: rarely-headache, dizziness, drowsiness; very rarely-convulsions; frequency unknown-paresthesia/hypesthesia.

Cardiac disorders: frequency unknown – rapid heartbeat.

Respiratory, thoracic and mediastinal disorders: rare-nosebleeds frequency unknown-upper respiratory tract infections pharyngitis cough sinusitis rhinorrhea Charge-Strauss syndrome.

Disorders of the gastrointestinal tract: rare-heartburn belching abdominal pain; frequency unknown-diarrhea vomiting dyspepsia nausea constipation pancreatitis dry mouth.

Liver and biliary tract disorders: rarely-increased activity of “hepatic” transaminases in the blood serum (alanine aminotransferase (ALT) aspartate aminotransferase (ACT)) very rarely – hepatitis (including cholestatic hepatocellular and mixed liver lesions).

Skin and subcutaneous tissue disorders: rarely-skin rash urticaria; frequency unknown-angioedema the appearance of ecchymoses erythema nodosum erythema multiforme pruritus.

Musculoskeletal and connective tissue disorders: rarely-arthralgia; frequency unknown-myalgia including muscle spasms.

Kidney and urinary tract disorders: frequency unknown-enuresis in children.

General disorders and disorders at the injection site: rarely-asthenia (weakness)/fatigue; frequency unknown-edema pyrexia thirst.

Levocetirizine

Immune system disorders: frequency unknown-hypersensitivity reactions including anaphylactic reactions.

Metabolic and nutritional disorders: frequency unknown-increased appetite increased body weight.

Mental disorders: often – headache drowsiness fatigue; infrequently-asthenia; frequency unknown-anxiety aggression agitation insomnia hallucinations depression suicidal thoughts.

Nervous system disorders: frequency unknown-seizures sinus thrombosis of the dura mater paresthesia dizziness syncope tremor dysgeusia (taste disorder).

Visual disturbances: frequency unknown – visual impairment diplopia inflammation blurred vision.

Hearing disorders and labyrinth disorders: frequency unknown-vertigo.

Cardiac disorders: frequency unknown-tachycardia angina palpitation sensation.

Vascular disorders: frequency unknown-jugular vein thrombosis.

Respiratory, thoracic and mediastinal disorders: frequency unknown-dyspnoea increased symptoms of rhinitis.

Disorders of the gastrointestinal tract: often – dry mouth; infrequently-abdominal pain; frequency unknown-nausea diarrhea vomiting.

Liver and biliary tract disorders: frequency unknown-hepatitis.

Skin and subcutaneous tissue disorders:frequency unknown-angioedema persistent drug-induced erythema rash pruritus urticaria hypotrichosis cracks photosensitization.

Musculoskeletal and connective tissue disorders: frequency unknown – muscle pain arthralgia.

Kidney and urinary tract disorders: frequency unknown-dysuria urinary retention urge to urinate.

Laboratory and instrumental data: frequency unknown-changes in liver function tests.

Other: frequency unknown-cross-reactivity peripheral edema.

If any of the side effects listed in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Montelukast

Montelukast can be prescribed together with other medications traditionally used for the prevention and long-term treatment of bronchial asthma and/or allergic rhinitis. The recommended therapeutic dose of montelukast does not have a clinically significant effect on the pharmacokinetics of the following drugs: theophylline. prednisone oral contraceptives prednisone (ethinyl estradiol / norethisterone 35/1) terfenadine digoxin and warfarin.

The AUC value decreases with simultaneous use of phenobarbital (by approximately 40%), but no correction of the dosage regimen of montelukast is required. Since montelukast is metabolized by the CYP 3 A 4 isoenzyme caution should be exercised if montelukast is co administered with drugs that induce the CYP 3 A 4 isoenzyme such as phenytoin phenobarbital and rifampicin. However, there is no need to change the dose of montelukast.

In vitro studies have shown that montelukast is a potential inhibitor of the CYP 2C8 isoenzyme; however, data from clinical drug – drug interaction studies involving montelukast and rosiglitazone (a preliminary substrate for medicinal products primarily metabolized by the CYP 2C8 isoenzyme) have shown that montelukast doses do not inhibit the CYP 2C8 isoenzymes in vivo. Consequently, montelukast does not significantly affect the metabolism of drugs metabolized by this enzyme (for example, paclitaxel rosiglitazone and repaglinide).

Gemfibrozil (a CYP 2C8 and 2C9 inhibitor) increases the systemic effect of montelukast by 44 times. However, the effect of gemfibrozil on the systemic effects of montelukast cannot be considered clinically significant based on safety data when using montelukast at doses exceeding the approved dose of 10 mg. Therefore, when co-administered with gemfibrozil, no dose adjustment of montelukast is required.

Co-use of itraconazole, a potent CYP3A4 inhibitor, together with gemfibrozil and montelukast did not lead to an additional increase in the effect of montelukast systemic exposure.

Levocetirizine

When studying the drug interaction of cetirizine racemate with phenazone pseudoephedrine cimetidine ketoconazole erythromycin azithromycin glipizide and diazepam, no clinically significant adverse interactions were detected.

Theophylline (400 mg/day) reduces the total clearance of levocetirizine by 16%, while the kinetics of theophylline does not change.

In a study with simultaneous use of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), it was shown that cetirizine exposure increased by 40% and ritonavir exposure changed slightly (-11%).

Concomitant use with macrolides or ketoconazole did not cause significant ECG changes.

In some cases, the concomitant use of levocetirizine with alcohol or drugs that have an overwhelming effect on the central nervous system (CNS) may increase their effect on the central nervous system, although it is not proven that cetirizine racemate potentiates the effect of alcohol.

How to take it, course of use and dosage

Inside with water, regardless of food intake.

Adults and children over 15 years of age: take 1 tablet once a day.

No dose adjustment is required in patients with hepatic insufficiency.

Patients with chronic renal failure and elderly patients should adjust the dose depending on the degree of renal failure.

In patients with mild renal impairment (creatinine clearance 50-79 ml/min), no dose adjustment is required.

In patients with moderate renal insufficiency (creatinine clearance from 30 to 49 ml/min), the recommended dose of levocetirizine is 5 mg (1 tablet) every other day.

In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), the recommended dose of levocetirizine is 5 mg (1 tablet) once every 3 days.

Duration of taking the drug

In the treatment of seasonal (intermittent) rhinitis (the presence of symptoms less than 4 days a week or their total duration is less than 4 weeks), the duration of treatment depends on the duration of symptoms; treatment can be discontinued when symptoms disappear and resumed when symptoms appear.

In the treatment of year-round (persistent) allergic rhinitis (the presence of symptoms more than 4 days a week and their total duration is more than 4 weeks), treatment can continue for the entire period of exposure to allergens.

If you miss one dose of the drug, you should not take an additional dose of the drug to compensate for the missed dose, it is recommended to take the next dose at the usual time.

Overdose

There were no reports of overdose with the drug. However, there is evidence of overdose of individual components of the drug.

Montelukast

Symptoms: The most common adverse events were thirst drowsiness vomiting psychomotor agitation headache and abdominal pain.

Treatment: treatment is symptomatic. There is no information about the specific treatment of montelukast overdose. There are no data on the possibility of removing montelukast by peritoneal dialysis or hemodialysis.

Levocetirizine

Symptoms: drowsiness (in adults) agitation and restlessness followed by drowsiness (in children).

Treatment: gastric lavage intake of activated charcoal symptomatic therapy. There is no specific antidote. Hemodialysis is ineffective.

Special instructions

Montelukast

In rare cases, patients taking medications for the treatment of bronchial asthma, including montelukast, may experience systemic eosinophilia, sometimes accompanied by clinical manifestations of vasculitis and Charge-Strauss syndrome. This condition is usually treated with systemic corticosteroids. Such cases are usually but not always associated with dose reduction or discontinuation of oral glucocorticosteroids. Doctors should be aware of the possibility that patients with eosinophilia may develop a vasculitis rash, an increase in pulmonary symptoms, cardiac complications, and / or neuropathy.

Patients with confirmed allergies to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during treatment with montelukast, as it improves respiratory function in patients with allergic bronchial asthma, but cannot completely prevent bronchoconstriction caused by NSAIDs.

Neuropsychiatric disorders have been reported in patients treated with montelukast. Given that these symptoms may have been caused by other factors, it is not known whether they are related to taking montelukast. The doctor should discuss these adverse events with patients and/or their parents / guardians. Patients and/or their parents/guardians should be told that if such symptoms occur, they should inform the attending physician.

Levocetirizine

During treatment with the drug, it is not recommended to take ethanol.

Influence on the ability to drive vehicles and mechanisms:

Studies of the effect of the drug on the ability to drive vehicles and mechanisms have not been conducted. During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, as the drug can cause weakness, drowsiness and dizziness.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Levocetirizine, Montelukast

Conditions of release from pharmacies

By prescription

Dosage form

Tablets