Montlezir, 5 mg+10 mg 10 pcs

A combined anti-allergic agent.

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

Montelukast selectively inhibits the CysLT receptors of the cysteinyl leukotrienes of the airway epithelium. Cysteinyl leukotriene type 1 receptors (CysLT receptors) are present in the human airway, including in bronchial smooth muscle cells, macrophages and other pro-inflammatory cells (including eosinophils and some myeloid stem cells).

The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) belong to the class of eicosanoids formed from arachidonic acid, and are mediators of inflammation formed in various cells of the body, including mast cells.Mast cells and eosinophils.

Cysteinyl leukotrienes correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In allergic rhinitis, the release of cysteinyl leukotrienes from the anti-inflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction occurs after allergen exposure, which manifests as symptoms of allergic rhinitis.

In an intranasal test with cysteinyl leukotrienes, an increase in symptoms of nasal obstruction has been demonstrated. Montelukast binds with high affinity and selectivity to CysLT1 receptors and reduces the number of eosinophils in peripheral blood, in the airways.

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

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

Levocetirizine prevents and facilitates the development of allergic reactions, has antiexudative, antipruritic effects; it has practically no anticholinergic and antiserotonin action. In therapeutic doses has almost no sedative effect.

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

Pharmacokinetics

Indications

Active ingredient

Composition

1 tablet:

How to take, the dosage

Ingestion with water, regardless of meals.

Adults and children over 15 years of age: Take 1 tablet once daily.

Patients with hepatic insufficiency do not need dose adjustment.

Patients with chronic renal failure and elderly patients should adjust the dose according to the degree of renal failure.

Patients with mild renal impairment (creatinine clearance 50-79 ml/min) do not require dose adjustment.

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

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

The duration of therapy

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

When treating year-round (persistent) allergic rhinitis (presence of symptoms more than 4 days per week and their total duration of more than 4 weeks), treatment may continue for the duration of allergen exposure.

If one dose of the drug is missed, no additional dose of the drug should be taken to compensate for the missed dose; it is recommended that the next dose be taken at the usual time.

Interaction

Montelukast

Montelukast can be prescribed 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 has no clinically significant effect on the pharmacokinetics of the following drugs: theophylline. prednisone, prednisolone, oral contraceptives (ethinylestradiol/norethisterone 35/1), terfenadine, digoxin and warfarin.

The AUC value decreases with concomitant administration of phenobarbital (approximately 40%), but correction of the dosing regimen of montelukast is not required. Since montelukast is metabolized by CYP 3A4 isoenzyme, caution should be exercised if montelukast is concomitantly administered with drugs that induce 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 representative of medical drugs primarily metabolized by CYP 2C8 isoenzymes) showed that montelukast doses do not inhibit CYP 2C8 isoenzymes in vivo.

Hence, montelukast has no marked effect on the metabolism of drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone and repaglinide).

Gemfibrozil (CYP 2C8 and 2C9 inhibitor) increases the effect of systemic exposure to montelukast by 4.4 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 higher than the approved dose of 10 mg. Therefore, no dose adjustment of montelukast is required when coadministered with gemfibrozil.

The co-administration of itraconazole, a potent CYP 3A4 inhibitor, together with gemfibrozil and montelukast did not result in an additional increase in the systemic effects of montelukast.

Levocetirizine

In studies of drug interactions of cetirizine racemate with phenazone, pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam no clinically significant adverse interactions were found.

Theophylline (400 mg/day) decreases total clearance of levocetirizine by 16% with no change in the kinetics of theophylline.

In a study with concomitant administration of ritonavir (600 mg twice daily) and cetirizine (10 mg daily), it was shown that cetirizine exposure was increased by 40% and ritonavir exposure was not significantly altered (-11%).

Co-administration with macrolides or ketoconazole did not cause significant changes in ECG.

In some cases, concomitant use of levocetirizine with alcohol or central nervous system (CNS)-inhibiting drugs may increase their effects on the CNS, although cetirizine racemate has not been shown to potentiate the effects of alcohol.

Special Instructions

Montelukast

In rare cases, patients taking bronchial asthma medications, including montelukast, may have systemic eosinophilia, sometimes accompanied by clinical manifestations of vasculitis and Churg-Strauss syndrome. This condition is usually treated with systemic glucocorticosteroids.

These cases are usually, but not always, associated with dose reduction or withdrawal of oral glucocorticosteroids. Physicians should be aware of the possibility of eosinophilia, vasculitic rash, increased pulmonary symptoms, cardiac and/or neuropathic complications in patients.

Patients with confirmed allergies to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs) should not take these medications during treatment with montelukast because while it improves respiratory function in patients with allergic bronchial asthma, it cannot completely prevent NSAID-induced bronchoconstriction.

In patients taking montelukast, neuropsychiatric disorders have been described. Given that these symptoms may have been caused by other factors, it is unknown whether they are related to taking montelukast.

The physician should discuss these adverse events with patients and/or their parents/guardians. Patients and/or their parents/guardians should be advised that if these symptoms occur, it is important to inform the treating physician.

Levocetirizine

It is not recommended to take ethanol during treatment with the drug.

Impact on driving and operating ability

There have been no studies of the effect of the drug on the ability to drive vehicles and operate machinery.

When using the drug, caution must be exercised while driving motor vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions, as the drug may cause weakness, drowsiness and dizziness.

Contraindications

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

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

The terminal stage of renal failure (creatinine clearance below 10 ml/min).

Children under 15 years of age (due to limited data on safety and effectiveness).

Pregnancy and breastfeeding.

With caution:

Chronic renal failure (dosing adjustment required); advanced age (decreased glomerular filtration may occur); patients with spinal cord injury, prostatic hyperplasia, and other predisposing factors to urinary retention, as levocetirizine may increase the risk of urinary retention; concomitant use with alcohol.

Side effects

The adverse events listed below are distributed by frequency of occurrence according to the following gradation: very common (≥ 1/10), common (≥ 1/100 to

Montelukast

Blood and lymphatic system disorders: frequency unknown – increased susceptibility to bleeding, thrombocytopenia.

Immune system disorders: rare – hypersensitivity reaction, including anaphylaxis, very rare – 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, somnolence; very rarely – seizures; frequency unknown – paresthesia/hypoesthesia.

Chronic disorders: frequency unknown – palpitations.

Respiratory system, chest and mediastinum disorders: rare – nasal bleeding, frequency unknown – upper respiratory tract infections, pharyngitis, cough, sinusitis, rhinorrhea, Churg-Strauss syndrome.

Gastrointestinal disorders: rare – heartburn, belching, abdominal pain; frequency unknown – diarrhea, vomiting, dyspepsia, nausea, constipation, pancreatitis, dry mouth.

Hepatic and biliary tract disorders: rare – increased activity of “hepatic” transaminases in serum (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), very rare – hepatitis (including cholestatic, hepatocellular and mixed liver lesions).

Skin and subcutaneous tissue disorders: rare – skin rash, urticaria; frequency unknown – angioedema, ecchymosis, erythema multiforme, pruritus.

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

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

General disorders and disorders at the site of administration: rarely – asthenia (weakness)/fatigue; frequency unknown – edema, pyrexia, thirst.

Levocetirizine

Immune system disorders: frequency unknown – hypersensitivity reactions, including anaphylactic reactions.

Metabolic and nutrition disorders: frequency unknown – increased appetite, increased body weight.

Mental disorders: frequent – headache, somnolence, fatigue; infrequent – asthenia; frequency unknown – anxiety, aggression, agitation, insomnia, hallucinations, depression, suicidal thoughts.

Nervous system disorders: frequency unknown – seizures, dura sinus thrombosis, paresthesia, dizziness, fainting, tremor, dysgeusia (taste disorder).

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

Hearing and labyrinth disorders: frequency unknown – vertigo.

Cardiac disorders: frequency unknown – tachycardia, angina pectoris, palpitations.

Vascular disorders: frequency unknown – jugular vein thrombosis.

Respiratory system, chest and mediastinum disorders: frequency unknown – dyspnea, increased symptoms of rhinitis.

Gastrointestinal disorders: frequent – dry mouth; infrequent – abdominal pain; frequency unknown – nausea, diarrhea, vomiting.

Liver and biliary tract disorders: frequency unknown – hepatitis.

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

Muscular 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 – change in liver function tests.

Other: frequency unknown – cross reactivity, peripheral edema.

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

Overdose

There have been no reports of overdose with the drug. However, there are data on overdose of individual components of the drug.

Montelukast

Symptoms: The most frequent adverse events were feeling of thirst, drowsiness, vomiting, psychomotor agitation, headache and abdominal pain.

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

Levocetirizine

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

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

Pregnancy use

There have been no adequate and strictly controlled clinical studies on the safety of the drug during pregnancy.

The use of the drug in pregnancy is contraindicated.

There are no data on excretion of Montelukast in human milk.

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