Montelukast - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 106.7 mg, mannitol 62.2 mg, croscarmellose sodium 7.5 mg, giprolose 0.8 mg, cellulose microcrystalline 9.0 mg, magnesium stearate 3.4 mg.

Tablet casing: Fill yellow 20A520007 (hypromellose (E 464) 40%, giprolose (E 463) 30%, titanium dioxide (E 171) 27.804%, carnauba wax (E 903) 1.25%, iron dye oxide yellow (E 172) 0, 88%, ferric iron oxide red (E 172) 0.066%) 5.0 mg.

Description:

Square with rounded corners of the tablet, covered with a film shell of pale orange with a brownish shade of color, with an engraving "I" on one side and "114" on the other.

On the cross section, the core of the tablet is white or almost white in color.

Pharmacotherapeutic group:Anti-inflammatory anti-bronchoconstrictive agent - leukotriene receptor blocker

ATX: & nbsp

R.03.D.C.03 Montelukast

Pharmacodynamics:

Cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are strong inflammatory mediators - eicosanoids, which are excreted by different cells, including mast cells and eosinophils. These important proastmatic mediators are linked to cysteinyl leukotriene receptors. Cysteinyl leukotriene type I receptors (CysLT₁receptors) 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 correlate with the pathophysiology of bronchial asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include bronchospasm, increased mucus secretion, increased vascular permeability, and an increase in the number of eosinophils. With allergic rhinitis after the exposure of the allergen, cysteinyl leukotrienes are released from the proinflammatory cells of the nasal mucosa during the early and late phases of the allergic reaction, which is manifested by the symptoms of allergic rhinitis.With an intranasal test with cysteinyl leukotrienes, an increase in the resistance of the airway nasal passages and symptoms of nasal obstruction was demonstrated.

Montelukast - highly active when administered a drug that significantly improves the rates of inflammation in bronchial asthma. According to biochemical and pharmacological analysis montelukast with high affinity and selectivity is associated with CysLT₁receptors without interacting with other pharmacologically important receptors in the airways (such as prostaglandin, cholinergic or β-adrenergic receptors). Montelukast inhibits the physiological action of cysteinyl leukotrienes LTC₄, LTD₄ and LTE₄ by binding to CysLT₁receptors, without exerting a stimulating effect on these receptors.

Montelukast inhibits CysLT-receptors in the respiratory tract, which is confirmed by the ability to block the development of bronchospasm in response to inhalation LTD₄ in patients with bronchial asthma. Doses of 5 mg are sufficient for arresting bronchospasm induced LTD₄.

Montelukast causes bronchodilation within 2 hours after ingestion and can supplement the bronchodilation caused by β2-adrenomimetics.

The use of montelukast in doses exceeding 10 mg per day, taken once, the effectiveness of the drug does not increase.

Pharmacokinetics:

Absorption and bioavailability

Montelukast quickly and almost completely absorbed after ingestion. The intake of normal food does not affect the bioavailability and maximum concentration in the plasma (C_m_Oh) Montelukast. In adults, when administered on an empty stomach of Montelukast in the form of coated tablets, C_m_Oh is achieved in 3 hours. Bioavailability with ingestion is 64%.

Distribution

Montelukast binds to plasma proteins more than 99%. Volume of distribution Montelukast in the equilibrium state averages 8-11 liters.

Concentration of montelukast 24 hours after taking the drug was minimal in all tissues of the body.

Metabolism

Montelukast is actively metabolized in the liver. When therapeutic doses are used, the concentration of montelukast metabolites in plasma in an equilibrium state in adults and in children is not determined. It is assumed that the metabolism of montelukast involves cytochrome P450 isoenzymes CYP 3A4 and 2C9, while in therapeutic concentrations montelukast Does not inhibit cytochrome P450 isoenzymes CYP: 3A4, 2C9, 1A2, 2A6, 2C19 and 2D6.

Excretion

The clearance of montelukast is 45 ml / min in healthy adults. After oral administration of montelukast, 86% of the dose taken is excreted through the intestine for 5 days and less than 0.2% by the kidneys, which confirms that montelukast and its metabolites are excreted almost exclusively with bile. The half-life in young healthy adults ranges from 2.7 to 5.5 hours.

The pharmacokinetics of montelukast retains a practically linear character when administered in doses over 50 mg. When taking montelukast in the morning and evening hours, there is no difference in pharmacokinetics. When taking montelukast 1 time per day in a dosage form, coated tablets, a moderate (about 14%) cumulation of the active substance in the plasma is observed.

Pharmacokinetics in different patient groups

Floor

The pharmacokinetics of montelukast in men and women is similar.

Age

When administered once daily montelukasta 10 mg pharmacokinetic profile and bioavailability are similar in the elderly and in young patients.

Ethnicity

There were no differences in clinically significant pharmacokinetic effects in patients of different races.

Renal insufficiency

Because the montelukast and its metabolites are excreted in bile to patients with renal failure, dose adjustment is not required.

Liver failure

Patients with hepatic insufficiency of mild and moderate severity and clinical manifestations of cirrhosis have a slowed metabolism montelukast, accompanied by an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) approximately 41% after a single dose of 10 mg. The excretion of montelukast in these patients is slightly increased in comparison with healthy people (mean half-life is 7.4 hours). Changes in the dose of montelukast for patients with mild to moderate hepatic insufficiency are not required. There is no data on the pharmacokinetics of montelukast with severe hepatic insufficiency (more than 9 on the Child-Pugh scale).

Indications:

- Long-term treatment and prevention of bronchial asthma, including the prevention of day and night symptoms of the disease.

- Treatment of bronchial asthma in patients with hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.

- Prevention of bronchospasm caused by exercise.

- Cupping of day and night symptoms of year-round and seasonal allergic rhinitis.

Contraindications:

- Hypersensitivity to any of the components of the drug;

- Children up to 15 years;

- Intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

Pregnancy and lactation:

Appointment of the drug Montelukast during pregnancy and during breastfeeding is possible only if the intended benefit to the mother exceeds the potential risk to the fetus or child.

There were reports of the development of birth defects in the limbs of newborns whose mothers were taking montelukast during pregnancy. Most of these women also took other medications to treat bronchial asthma during pregnancy. The causal relationship between the administration of montelukast and the development of birth defects of the limbs has not been established.

It is not known whether montelukast with breast milk.

Dosing and Administration:

Inside, once a day, regardless of food intake. For treatment of bronchial asthma, the drug should be taken in the evening.In the treatment of allergic rhinitis drug can be taken at any time of the day at the request of the patient.

Adults and children from 15 years: 1 tablet (10 mg) per day.

General recommendations

Therapeutic effect of the drug Montelukast on the symptoms that reflect the course of bronchial asthma manifests itself during the first day. Patient should continue taking the drug Montelukast as in the period of controlled course of bronchial asthma, and during the exacerbation of the disease.

For elderly patients, patients with renal insufficiency, patients with mild or moderate liver function disorders, dose adjustment is not required. The dose of the drug is the same for both female and male patients.

Appointment of the drug Montelukast simultaneously with other types of asthma treatment

Montelukast can be added to the treatment of the patient with bronchodilators and inhaled glucocorticosteroids (see section "Interaction with other drugs").

Side effects:

In general, the drug Montelukast well tolerated. Side effects are usually mild and, as a rule, do not require withdrawal of treatment.The overall incidence of side effects reported with the use of montelukast is comparable to that of placebo.

Violations from the blood and lymphatic system:

Increased propensity to bleed, "thrombocytopenia."

Immune system disorders:

Hypersensitivity reactions, including anaphylaxis, eosinophilic liver infiltration (very rarely - <0.01%).

Disorders of the psyche:

Agitation, including aggressive behavior or hostility, anxiety, depression, disorientation, pathological dreams, hallucinations, insomnia, irritability, anxiety, somnambulism, suicidal ideation and behavior (suicidal), tremor, attention disturbance, memory impairment, psychomotor activity.

Impaired nervous system:

Headache, dizziness, drowsiness, paresthesia / hypoesthesia, hyperkinesia, convulsions (very rarely <0.01%).

Heart Disease:

Cardiopalmus.

Disturbances from the respiratory system, chest and mediastinal organs:

Nasal bleeding, upper respiratory tract infection, pharyngitis, cough, sinusitis, rhinorrhea, "pulmonary eosinophilia".

Disorders from the gastrointestinal tract:

Diarrhea, dyspepsia, nausea, vomiting, pancreatitis, abdominal pain, dry mouth.

Disorders from the liver and bile ducts:

Increased activity of "liver" transaminases in the blood serum (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), hepatitis (including cholestatic, hepatocellular and mixed liver damage) (very rarely - <0.01%).

Disturbances from the skin and subcutaneous tissues:

Angioedema, appearance of ecchymosis, erythema nodosum, erythema multiforme, itching, rash, urticaria.

Disturbances from the musculoskeletal and connective tissue:

Arthralgia, myalgia, including muscle spasms.

Disorders from the kidneys and urinary tract:

Enuresis in children.

General disorders and disorders at the site of administration:

Asthenia (weakness) / fatigue, swelling, pyrexia, thirst. In rare cases, patients with bronchial asthma develop the syndrome of Chardz-Strauss.

Overdose:

Symptoms: Data on the symptoms of overdose when taking the drug by patients with bronchial asthma at a dose exceeding 200 mg per day for 22 weeks and at a dose of 900 mg per day for 1 week was not revealed. There have been cases of acute overdose (taking at least 1000 mg of the drug per day).The most frequent adverse events were thirst, drowsiness, mydriasis, hyperkinesia and abdominal pain, vomiting, psychomotor agitation, headache.

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

Interaction:

A drug Montelukast can be prescribed together with other drugs that are commonly used for the prevention and long-term treatment of bronchial asthma and / or the treatment of allergic rhinitis. The recommended therapeutic dose of montelukast had no clinically significant effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol / norethisterone 35/1), terfenadine, digoxin and warfarin.

Value AUC montelukast decreases with simultaneous reception of phenobarbital by about 40%, but this does not require changes in the dosage regimen of the drug Montelukast.

In studies in vitro determined that montelukast inhibits isoenzyme CYP 2C8 of the cytochrome P450 system, however, in the study of the drug interaction in vivo Montelukast and rosiglitazone (metabolized with the participation of isoenzyme CYP 2C8 of the cytochrome P450 system) it was shown that montelukast did not inhibit isoenzyme CYP 2C8. Thus, the effect of Montelukast on CYP 2C8-mediated metabolism of medications (eg, paclitaxel, rosiglitazone, repaglinide). Research in vitro showed that montelukast is a substrate of isoenzymes CYP 2C8, 2C9 and 3A4. Data from the clinical trial of drug interaction for montelukast and gemfibrozil (an inhibitor of both CYP 2C8, and 2C9) demonstrate that gemfibrozil increases the effect of systemic exposure of Montelukast 4.4 times. Joint use of itraconazole, a potent inhibitor CYP Z3A4, together with gemfibrozil and montelukast did not lead to an additional increase in the effect of systemic exposure to montelukast. The effect of gemfibrozil on systemic exposure to montelukast can not be considered clinically significant on the basis of safety data when administered at doses exceeding the approved dose of 10 mg for adult patients (eg,When used at a dose of 200 mg / day for adult patients for 22 weeks and up to 900 mg / day for about one week, no clinically significant adverse effects were observed.) Thus, with a co-administration with gemfibrozilom adjustment of the dose of montelukast is not required. Based on research results in vitro no clinically significant drug interactions with other known inhibitors CYP 2C8 (for example, with trimethoprim). In addition, the joint administration of montelukast with itraconazole alone did not result in a significant increase in the effect of systemic exposure to montelukast.

Combined treatment with bronchodilators

A drug Montelukast is a justified addition to monotherapy with bronchodilators if the latter do not provide adequate control of bronchial asthma. Upon achievement of the therapeutic effect of drug treatment Montelukast it is possible to begin a gradual decrease in the dose of bronchodilators.

Combined treatment with inhaled glucocorticosteroids

Treatment with drug Montelukast provides an additional therapeutic effect to patients using inhaled glucocorticosteroids.Once the stabilization of the condition is achieved, a gradual decrease in the dose of the glucocorticosteroid can be started under the supervision of the physician. In some cases, complete cancellation of inhaled glucocorticosteroids is permissible, but a sharp substitution of inhaled glucocorticosteroids for the drug Montelukast Not recommended.

Special instructions:

Effectiveness of the drug Montelukast for oral administration with respect to the treatment of acute attacks of bronchial asthma is not established, so the drug Montelukast in tablets not It is recommended to prescribe for treatment of acute attacks of bronchial asthma. A drug Montelukast should not replace inhaled or oral glucocorticosteroids. There are no data indicating the possibility of reducing the dose of oral glucocorticosteroids with the concomitant use of the drug Montelukast.

In patients receiving montelukast, psychoneurological disturbances have been described (see the "Side effect" section). Given that these symptoms could be caused by other factors, it is not known whether they are associated with taking montelukast. The doctor should discuss this undesirable phenomenon with patients and / or their parents / guardians.Patients and / or their parents / caregivers need to be explained that in case of such symptoms it is necessary to inform the attending physician about it.

In rare cases, patients taking drugs to treat bronchial asthma, including the drug Montelukast, there may be systemic eosinophilia, sometimes accompanied by clinical manifestations of vasculitis and the syndrome of Chardz-Strauss. This condition is usually treated with systemic glucocorticosteroids. Such cases are usually, but not always, associated with a decrease in dose or with the elimination of oral glucocorticosteroids. We can neither exclude nor confirm the likelihood that the reception of leukotriene receptor antagonists can be associated with the emergence of the Charge-Strauss syndrome. Doctors should be aware of the possibility of patients developing eosinophilia, vasculitic rash, an increase in pulmonary symptoms, complications from the heart and / or neuropathy. Patients who have the above symptoms should undergo a second examination, and their treatment regimen should be reviewed.

The drug is not used to stop attacks of bronchial asthma as an emergency medicine, but its reception should not be discontinued during the period of exacerbation.

Patients with a confirmed allergy to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) should not take these drugs during the treatment with the drug Montelukast, as it, improving respiratory function in patients with allergic bronchial asthma, nevertheless, can not completely prevent bronchoconstriction caused by NSAIDs.

Effect on the ability to drive transp. cf. and fur:

Data indicating that the administration of montelukast affects the ability to drive a car or moving machinery has not been identified. However, when the drug is used, there are side effects such as dizziness and drowsiness. In view of this, care should be taken when driving vehicles and work requiring quickness of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 10 mg.

Packaging:

For 7 or 10 tablets in a blister of PVC-Al-OPA / Al.

For 1, 2 or 4 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004252

Date of registration:18.04.2017

Expiration Date:18.04.2022

The owner of the registration certificate:Heterose Labs LimitedHeterose Labs Limited India

Manufacturer: & nbsp

HETERO LABS, Limited India

Representation: & nbspHeterose Labs LimitedHeterose Labs LimitedIndia

Information update date: & nbsp08.06.2017

Illustrated instructions

Instructions

Montelukast (Montelukast)