Montlezir pills 5mg+10mg, 10pcs

Composition

of 1 tab. :

• Active ingredient of the 1st layer: levocetirizine dihydrochloride 5.0 mg;
• Excipients of the 1st layer: 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;
• Active ingredient 2 layers: montelukast sodium 10.4 mg, equivalent to montelukast 10.0 mg;
• Excipients 2 layers: 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

Combined anti-allergic agent.

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 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, reduces the number of eosinophils in the peripheral blood and in the respiratory tract.

Levocetirizine is a histamine_H1-receptor blocker, R-enantiomer of cetirizine; a competitive histamine antagonist; affinity with histamine_H1-receptors is 2 times higher than that of cetirizine.

Levocetirizine has an effect on the histamine-dependent stage of allergic reactions; it reduces the migration of eosinophils, reduces vascular permeability, and 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 anti-exudative, 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

Montelukast

Montelukast is rapidly and almost completely absorbed after oral use. Regular food intake does not affect the bioavailability and_cmax of montelukast. The binding of montelukast to plasma proteins is more than 99%. Vd averages 8-11 l. Montelukast is actively metabolized in the liver.

When used in therapeutic doses, plasma concentrations of montelukast metabolites at steady state in adults and children are not determined.

It is assumed that the metabolism of montelukast involves the isoenzymes CYP3A4 and CYP2C9, while at therapeutic concentrations montelukast does not inhibit the isoenzymes CYP3A4, CYP2C9, CYP1A2, CYP2A6, CYP2C19 and CYP2D6.

The clearance of montelukast is on average 45 ml/min in healthy adults. After oral use of montelukast,86% of the dose is excreted through the intestine 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. T_1/2 in healthy adults is from 2.7 to 5.5 h

. 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 1 time/day in the dose of montelukast in the dosage form of film-coated tablets 10 mg, moderate (about 14%) accumulation of the Active ingredient in 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, _{and csss} is reached in 2 days. Levocetirizine is 90% bound to plasma proteins. V_d – 0.4 l / kg.

In humans, less than 14% of the levocetirizine dose is metabolized, since the estimated differences in the pharmacokinetic profile of levocetirizine due to genetic polymorphism or simultaneous use 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 CYP3A4 isoenzyme, while the oxidation of the aromatic ring occurs with the help of many and/or unidentified CYP isoforms.

Levocetirizine when administered at a dose of 5 mg and/or in excess of C_max in blood plasma has no effect on the activity of the isoenzymes 2 AND CYP1, CYP2,9, CYP2 19, CYP2D6, E 1 CYP2, CYP3 AND 4. Due to limited metabolism and absence of metabolic inhibition activity, the interaction of levocetirizine on the level of the metabolism of other substances is unlikely.

T_1/2 of levocetirizine in adults is 7.9±1.9 h. The average observed total clearance is 0.63 ml / min / kg. Completely eliminated from the body within 95 hours. About 85.4% of the drug dose is excreted by the kidneys, about 12.9% – through the intestines.

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), T_1/2 – 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 cirrhosis, a slowdown in montelukast metabolism was observed, accompanied by an increase in AUC of approximately 41% after a single dose of 10 mg of montelukast. T_1/2 of montelukast in patients with hepatic insufficiency is slightly increased compared to healthy volunteers (mean T_1/2 – 7.4 hours).

In patients with renal insufficiency with creatinine clearance 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. In children aged 6 to 11 years with a body weight of 20 to 40 kg, when taking 5 mg of levocetirizine once_{, the cmax} and AUC values are approximately 2 times higher than 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 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), as well as to 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 safety and efficacy data).

Pregnancy and breast-feeding period.

With caution:

Chronic renal failure (dosage adjustment is required); advanced age (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 following adverse events are distributed according to the frequency of occurrence in accordance with the following gradation: very common (≥ 1/10), common (≥ 1/100 to

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, abnormal 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: rarely-nosebleeds, frequency unknown-upper respiratory tract infections, pharyngitis, cough, sinusitis, rhinorrhea, Charge-Strauss syndrome.

Gastrointestinal disorders: rarely-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, ecchymosis, erythema nodosum, erythema multiforme, pruritus.

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

Renal 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, dura mater sinus thrombosis, paresthesia, dizziness, fainting, tremor, dysgeusia (taste disorder).

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

Hearing disorders and labyrinth disorders: frequency unknown-vertigo.

Cardiac disorders: frequency unknown-tachycardia, angina pectoris, palpitation sensation.

Vascular disorders: frequency unknown-jugular vein thrombosis.

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

Gastrointestinal disorders: 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.

Renal 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, prednisone, oral contraceptives (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 3A4 isoenzyme, caution should be exercised if montelukast is co-administered with drugs that induce the CYP 3A4 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, but 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 that are metabolized by this enzyme (for example, paclitaxel, rosiglitazone and repaglinide).

Gemfibrozil (a CYP 2C8 and 2C9 inhibitor) increases the effect of montelukast systemic exposure by 4.4 times. However, the effect of gemfibrozil on the systemic exposure 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.

Concomitant 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%, while 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 has not been proven that cetirizine racemate potentiates the effect of alcohol.

How to take, course of use and dosage

Inside, washed down 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, taking 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 potential for patients to develop eosinophilia, vasculitis, increased 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 advised 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 motor vehicles and manage 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.

Active ingredient

Levocetirizine, Montelukast

Conditions of release from pharmacies

By prescription

Dosage form

Tablets