SYNHULYAR

Active material: Montelukast
When ATH: R03DC03
CCF: Leukotriene receptor antagonists. The drug for treatment of bronchial asthma and allergic rhinitis.
ICD-10 codes (testimony): J30.1, J30.3, J45
At KFU: 12.05.02
Manufacturer: MERCK SHARP & DOHME B.V.. (Netherlands)

Pharmaceutical form, composition and packaging

Chewable Tablets Pink colour, Oval, lenticular, embossed with the inscription “SINGULAIR” on one side and “MSD 711” – another.

Excipients: mannitol, microcrystalline cellulose, giproloza, iron oxide red, Croscarmellose sodium, cherry flavor, Aspartame, magnesium stearate.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

Chewable Tablets Pink colour, round, lenticular, embossed with the inscription “MSD 275” on one side and “SINGULAIR” – another.

Excipients: mannitol, microcrystalline cellulose, giproloza, iron oxide red dye, Croscarmellose sodium, cherry flavor, Aspartame, magnesium stearate.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

Pills, coated light cream color, square, with rounded edges, Engraved “MSD 117” on one side and “SINGULAIR” – another.

Excipients: microcrystalline cellulose, lactose, Croscarmellose sodium, giproloza, magnesium stearate.

The composition of the shell: giproloza, gipromelloza, Titanium dioxide, dyes iron oxide red and iron oxide yellow, carnauba wax.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

Pharmacological action

Leukotriene receptor antagonists. Montelukast inhibits the cysteinyl leukotriene receptor airway epithelium, showing at the same time the ability to inhibit bronchoconstriction, caused by the inhalation of cysteinyl-leukotriene LTD₄ in patients with bronchial asthma. Doses 5 mg is sufficient for the relief of bronchospasm, induced LTD₄. Use of montelukast at doses, exceeding 10 mg / day 1 time / day, It does not increase the effectiveness of the drug.

Montelukast causes bronchodilation within 2 hours after ingestion, and can complement bronchodilation, called beta₂-adrenomimetikami.

Pharmacokinetics

Absorption

After oral montelukast rapidly and almost completely absorbed from the gastrointestinal tract. Admission of ordinary food does not affect the C_max in plasma and the bioavailability of tablets, coated, and chewable tablets. In adults, when taking the tablets on an empty stomach, coated, dose 10 mg C_max plasma levels achieved after 3 no. Oral bioavailability is 64%.

After oral administration of the drug on an empty stomach in the form of chewable tablets in dose 5 mg C_max in adults is achieved through 2 no. Bioavailability is 73%.

Distribution

Binding montelukast plasma proteins is more than 99%. V_d averages 8-11 l.

In single dose of the drug in tablet form, coated, dose 10 mg 1 time / day there was a fair (about 14%) accumulation of active substance in plasma.

Metabolism

Montelukast actively metaboliziruetsya in baked. When used in therapeutic doses montelukast metabolite concentrations in plasma at steady state in adults and children not determined.

Expected, in the metabolism of montelukast involved cytochrome P450 isoenzymes (3A4 and 2C9), wherein at therapeutic concentrations montelukast does not inhibit cytochrome P450 isozymes: 3A4, 2C9, 1A2, 2A6, 2A19 and 2D6.

Deduction

T_1/2 montelukast in young healthy adults is 2.7 to 5.5 no. Clearance of montelukast in healthy adults average 45 ml / min. Following oral administration of montelukast 86% excreted in the feces within 5 days or less 0.2% – urine, that confirms, that montelukast and its metabolites are excreted almost exclusively in the bile.

Pharmacokinetics in special clinical situations

The pharmacokinetics of montelukast retains substantially linear when administered over 50 mg.

When receiving montelukast in the morning and evening differences in the pharmacokinetics are not observed.

The pharmacokinetics of montelukast in women and men has a similar character.

If ingestion of pills, coated, dose 10 mg 1 time / day pharmacokinetic profile and bioavailability have a similar in elderly patients and younger.

Patients with hepatic insufficiency mild to moderate severity and clinical manifestations of liver cirrhosis observed slowing metabolism of montelukast, accompanied by an increase in AUC of approximately 41% after a single dose of the drug at a dose of 10 mg. Excretion of Montelukast from several of these patients increased compared to healthy subjects (T_1/2 averages 7.4 no). Changing the dose of montelukast in patients with hepatic insufficiency mild to moderate severity is not required. Data on the nature of the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more 9 points on the Child-Pugh) no.

Because montelukast and its metabolites are not excreted in the urine, The pharmacokinetics of montelukast in patients with renal insufficiency has not been assessed. Correction of the dose in these patients is not required.

There were no clinically significant differences in pharmacokinetic effects in patients, depending on the race.

Testimony

Prevention and long-term treatment of asthma in adults and children 2 and older, including:

- Prevention of daytime and nighttime symptoms;

- The treatment of asthma in patients with hypersensitivity to acetylsalicylic acid;

- Prevention of bronchospasm, exercise-induced.

Relief of daytime and nighttime symptoms of seasonal allergic rhinitis (in adults and children 2 and older) and permanent allergic rhinitis (in adults and children 2 and older).

Dosage regimen

The drug is taken orally 1 time / day regardless of the meal. To asthma treatment Synhulyar^® should be taken in the evening. At treatment of allergic rhinitis the drug can be taken any time of day. When comorbidity (asthma and allergic rhinitis) the drug should be taken in the evening.

Adults and adolescents aged 15 and older the drug is prescribed in a dose 10 mg (1 tab., coated liner)/d.

Children aged 6 to 14 years administered at a dose of 5 mg (1 tab. Chewing)/d. Dose selection in this age group is not required.

Children aged 2 to 5 years for the treatment of asthma and / or allergic rhinitis the drug is prescribed in a dose 4 mg (1 tab. Chewing)/d.

The therapeutic effect of SINGULAIR^® on performance, reflecting for asthma, develops during the first day. Patients should continue taking Singulair^® in period to achieve control of asthma symptoms, and during acute illness.

To elderly patients, patients with renal insufficiency, Patients with mild or moderate hepatic impairment, as well as based on gender specific dose adjustment is not required.

Synhulyar^® can be added to treatment with bronchodilators and inhaled corticosteroids.

Side effect

Allergic reactions: anaphylaxis, angioedema, rash, itch, hives; rarely – eosinophil infiltration Pechenik.

CNS: strange vivid dreams, hallucinations, drowsiness, irritability, excitation, including aggressive behavior, fatiguability, suicidal thoughts and suicidal behavior (siutsidalnost), insomnia, paresthesia / gipestezii, headache; rarely – seizures.

From the digestive system: nausea, vomiting, diarrhea, stomach ache; rarely – cholestatic hepatitis, hepatocyte damage, often with concurrent drug therapy or liver disease (alcohol and other forms of hepatitis).

On the part of the musculoskeletal system: arthralgia, myalgia, including muscle cramps.

Dermatological reactions: uzlovataya эritema, tendency to bruising (Gemato).

Other: the trend to increased bleeding, heartbeat, swelling, in children between the ages of 2 to 5 years – thirst.

Overall Singulair^® well tolerated. Side effects are usually mild and usually did not require discontinuation of treatment. The overall incidence of side effects, It reported the application of SINGULAIR^®, comparable with that of placebo.

Contraindications

- Children up to age 2 years;

- Hypersensitivity to the drug.

Pregnancy and lactation

Synhulyar^® It should be used during pregnancy and lactation only in cases, the expected benefit to the mother outweighs the potential risk to the fetus or child.

Cautions

Synhulyar^® not recommended for treatment of acute asthma attacks. In acute bronchial asthma patients should be prescribed drugs for therapy, the acute attacks of the disease and warning.

Patients with asthma are always recommended to carry emergency medications (короткодействующие ингаляционные агонисты b-адренорецепторов).

For relief of acute attacks of asthma after exercise use the drug for relief of an attack, ie. короткодействующий ингаляционный агонисты b-адренорецепторов. Treatment SINGULAIR^® It does not guarantee absolute prevention of exacerbations.

During an exacerbation of asthma and the need for cupping drugs emergency (короткодействующих ингаляционных агонистов b-адренорецепторов) stop taking the drug Singulair^® should not.

The dose used in conjunction with singular^® Inhaled corticosteroids can reduce gradually under medical supervision. Do not abruptly replace singular^® therapy with inhaled or oral corticosteroids.

Patients with confirmed allergy to acetylsalicylic acid and other NSAIDs should be the period of treatment Singulair^® Avoid contact with these drugs, as Singulair^®, improving pulmonary function in patients with allergic bronchial asthma, Nonetheless, It does not prevent bronchoconstriction, due to the action of NSAIDs.

Reducing systemic dose corticosteroids in patients, receiving antiasthmatics, including leukotriene receptor antagonists, rarely accompanied by the appearance of one or more of the following phenomena: eozinofilii, purpura, worsening symptoms of the lung, Cardiac complications and / or neuropathy, sometimes diagnosed as Churg-Strauss syndrome – sistemnыy эozinofilynыy vasculitis. Although the causal relationship of adverse events with leukotriene receptor antagonist therapy has not been established, while reducing the systemic dose corticosteroids in patients, taking Singulair^®, Care should be taken to carry out the relevant clinical observation.

Age differences of efficacy and safety profile of SINGULAIR^® not found.

Patients with phenylketonuria should be informed that, what in 1 chewable tablets contain not less than 1.2 mg of aspartame.

Effects on ability to drive vehicles and operate machinery

Data, testifying, that taking SINGULAIR^® It affects the ability to drive or moving mechanisms have been identified.

Overdose

Symptoms Singulair overdose^® in patients with chronic bronchial asthma when used in a dose of, exceeding 200 mg / day, during 22 weeks at a dose 900 mg / day – during 1 of the week, not identified.

There have been reports of acute overdose of montelukast in children (at a dose of at least 150 mg / day). Clinical and laboratory data at the same time indicate the safety profile of SINGULAIR compliance^® children safety profile in adults and elderly patients. The most common adverse events were thirsty, drowsiness, midriaz, hyperkinesias, and abdominal pain.

Treatment: symptomatic therapy.

Data on possible elimination of montelukast by peritoneal dialysis or hemodialysis missing.

Drug Interactions

Synhulyar^® can be administered together with other drugs, conventionally used for the prevention and long term treatment of asthma. Montelukast at the recommended clinical dose no clinically meaningful effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol / norethindrone 35/1), terfenadine, digoxin and warfarin.

Patients, simultaneously receiving phenobarbital, The AUC of montelukast decreased by about 40%. Titration singular^® for this category of patients is not required.

With the ineffectiveness of bronchodilators as a single agent asthma treatment Singulair can be added^®. When the therapeutic effect (usually after the first dose) during therapy with SINGULAIR^® bronchodilator dose can gradually reduce.

Treatment SINGULAIR^® It provides additional therapeutic effects in patients, receiving inhaled corticosteroids. Following stabilization, patients may reduce the dose of GCS. The dose of corticosteroids should be reduced gradually, under the supervision of a physician. Some patients receiving inhaled corticosteroids can be fully repealed. We do not recommend sharp replacement therapy with inhaled corticosteroids singular purpose^®.

In in vitro studies found, that montelukast inhibits CYP2C8 isozyme. However, in the study of drug interactions in vivo montelukast and rosiglitazone (metabolized with the participation of the CYP2C8 isoenzyme) not received confirmation of the inhibition of CYP2C8 isoenzymes montelukast. Thus, in clinical practice is not expected to impact on montelukast CYP2C8-mediated metabolism of some drugs, incl. paclitaxel, Rosiglitazone, repaglinida.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. Chewable Tablets 5 mg and tablets, coated, 10 mg should be stored in a location protected from moisture and the dark place at a temperature of no higher than 30° c. Chewable Tablets 4 mg should be stored in a dry and dark place at a temperature of 15 ° C to 30 ° C. Shelf life chewable tablets – 2 year; tablets, coated, – 3 year.

The drug should be stored out of reach of children.