These important mediators bind proastmaticheskie cysteinyl-leukotriene receptors (CysLT), present in the human airway and bronchospasm responsible for reaction, sputum, vascular permeability and increase in the number of eosinophils.
Testosterone enanthate vs propionate active compound at peroral admission that possesses high affinity and selectivity to the CysLTi-receptors. Bronchodilatory effect observed within 2 hours after oral administration.
Bronchodilator effect betag-agonists is enhanced while taking montelukast. Inhibits both early and late stages of bronchospasm caused by exposure to antigens. Montelukast reduces the number of eosinophils in the peripheral blood of adults and children and also significantly reduces the number of eosinophils in the airways. Patients with hypersensitivity to aspirin receiving inhaled and / or oral glucocorticosteroids (GCS), the addition to montelukast therapy provides better control of the disease.
After oral montelukast is rapidly and almost completely absorbed. In adult patients on an empty stomach after ingestion tablets, film-coated tablets, 10 mg average value of the maximum plasma concentration (C max ) reached after 3 h. Bioavailability The mean value – 64%. Values with oral bioavailability and C max is not violated when eating.
The binding of montelukast with plasma proteins is 99%. The volume of distribution at equilibrium averages 8-11 liters. Preclinical studies showed minimal penetration of the blood brain barrier montelukast.After 24 hours, after ingestion of Montelukast negligible concentration in other tissues.
Montelukast is extensively metabolised in the liver. When used in therapeutic doses montelukast metabolite concentration in blood plasma at steady state is not determined in adults and children.
In vitro studies have shown that the metabolism of montelukast involved isozymes of cytochrome P450 (ZA4, 2A6 and 2C9), with therapeutic concentrations of montelukast does not inhibit cytochrome P450 isozymes: ZA4, 2C9, 1A2, 2A6, 2C19 and 2D6. The metabolites have little therapeutic effect of montelukast.
half-life of montelukast in healthy young adult volunteers ranges from 2.7 to 5.5 hours. The plasma clearance of montelukast in healthy adult volunteers averages 45 ml / min. Following oral administration of montelukast 86% of the total output through the intestine for 5 days and less than 0.2% – in the kidneys, which along with its bioavailability data confirms removal of Montelukast and its metabolites predominantly in the bile.
Pharmacokinetics in special clinical situations
The pharmacokinetics of montelukast in women and men the same.
Patients of advanced age or patients with hepatic insufficiency, mild to moderate severity is not required montelukast correction mode.
The pharmacokinetics of montelukast in patients with renal insufficiency has not been evaluated. Because montelukast and its metabolites are not excreted by the kidneys, a dose adjustment in these patients is not required. Data on the nature of the pharmacokinetics of montelukast in patients with severe hepatic impairment (more than 9 points on a scale Child-Pugh) do not. When high doses of montelukast (20 and 60 times the recommended dosage for adults) a decrease in the concentration of theophylline in blood plasma.
When taken in the recommended doses of montelukast 10 mg 1 time per day for this effect is not observed.
Indications for use:
Prevention and long-term treatment of asthma in adults and adolescents from 15 years, including:
- Warning daytime and nighttime symptoms of the disease;
- treatment of asthma in patients with hypersensitivity to acetylsalicylic acid;
- bronchospasm prevention of exercise-induced;
The relief of symptoms testosterone enanthate vs propionate of seasonal and perennial allergic rhinitis (in adults and adolescents from 15 years of age).
- hypersensitivity to the active or any excipient of the drug;
- Children up to age 15 years;
- Patients with rare hereditary disease: galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Application of pregnancy and during breastfeeding
Use of the drug during pregnancy is possible Montelast if the expected benefit to the mother outweighs the potential risk to the fetus. The decision on cancellation of breastfeeding for the period of application of the drug Montelast adopted on the basis of assessment of the expected benefits to the mother and the potential risk for the baby.
Dosage and administration:
The inside is not liquid, with plenty of fluids, regardless of the meal.
Adults and adolescents from 15 years old to take 1 tablet of the drug Montelast 10 mg daily in the evening.
therapeutic effect Montelast drug, allowing to control asthma symptoms is achieved within days after administration. Patients are advised to continue taking the drug as a controlled flow during periods of asthma, and in the period of exacerbation of bronchial asthma.
The drug Montelast should not be taken together with other products containing the same active ingredient – montelukast.
Elderly patients, patients with renal insufficiency and in patients with hepatic insufficiency easy and moderate a special dose adjustment is required. No dose adjustment is required, depending on the sex of the patient.
There is no data on the use of montelukast in patients with severe hepatic impairment.
Montelast drug can be added to the patient’s treatment with bronchodilators and inhaled corticosteroids.
Inhaled corticosteroids: Montelast drug can be prescribed for the treatment of asthma as add-on therapy for patients in whom inhaled corticosteroids and used as necessary beta-agonists of short action do not provide the necessary clinical management of the disease. The drug should not be abruptly replaced Montelast treatment with inhaled corticosteroids.
For the treatment of patients 2 to 15 years are available for different dosage form Tablets Chewable drug.
Infectious and parasitic diseases:
upper respiratory tract infection.
Violations of the blood and lymphatic system:
increasing the propensity to bleeding, thrombocytopenia.
Violations of the immune system:
hypersensitivity reactions, including anaphylaxis, hepatic eosinophilic infiltration.
abnormal dreams, including nightmares; hallucinations, insomnia, somnambulism, irritability, anxiety, restlessness; agitation including aggressive behavior or hostility; tremor, depression, disorientation, suicidal ideation and behavior (suicidality).
Disorders of the nervous system:
headache, dizziness, somnolence, paresthesia / hypoesthesia, seizures.
Violations of the heart:
Disorders of the respiratory system, organs, thoracic and mediastinal disorders:
Disorders of the gastrointestinal tract:
diarrhea, dry mouth, dyspepsia, nausea, vomiting, abdominal pain, pancreatitis.
Disorders of the liver and biliary tract:
increased activity of alanine aminotransferase and aspartate aminotransferase, hepatitis (including cholestatic, hepatocellular, and mixed liver injury).
Disorders of the skin and subcutaneous tissue disorders:
angioneurotic edema, tendency to bruising, urticaria, pruritus, rash, erythema nodosum, erythema multiforme.
Violations of the musculoskeletal and connective tissue disorders:
arthralgia, myalgia including muscle cramps.
General disorders and administration site at:
asthenia / fatigue, malaise, edema, pyrexia, thirst. In very rare cases during treatment with montelukast was reported on the development of the syndrome Chardjui-Strauss (see section Cautions).
Symptoms of drug overdose in patients with chronic bronchial asthma patients when used in a dose exceeding 200 mg per day for 22 weeks and 900 mg per day – 1 week, were not identified.
There have been reports of acute overdose of montelukast (upon receipt of not less than 1 g per day) in the post-marketing period and in clinical studies in adults testosterone enanthate vs propionate and children. Clinical and laboratory data at the same time show under the drug safety profile in children, adults and elderly patients. The most common symptoms are thirst, drowsiness, vomiting, agitation, headache, and abdominal pain.
Treatment: symptomatic therapy. Information about the possibility of montelukast excretion by peritoneal dialysis or hemodialysis are absent.
Interaction with other drugs
Patients treated simultaneously phenobarbital, area under the curve “concentration-time” montelukast decreased by approximately 40%, but the correct dosing regimen in these patients is not required.
Since montelukast is metabolized by isoenzyme of CYP3A4, caution should be exercised, particularly in children, when montelukast is used simultaneously with inducers of CYP3A4 isoenzyme, such as phenytoin, phenobarbital and rifampicin. Montelukast can be administered together with other drugs traditionally used for the prevention and long term treatment of asthma and / or allergic rhinitis.
Montelukast at the recommended therapeutic dose did not have a clinically meaningful effect on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol / norethynodrel 35/1), terfenadine, digoxin and warfarin.
In studies in vitro found that Montelukast is a potent inhibitor of isozyme CYP2C8. However, in the study of drug interactions in vivo montelukast and rosiglitazone (a marker substrate representative of drugs primarily metabolized by isoenzyme CYP2C8) received montelukast confirm inhibition of CYP2C8 isoenzymes. Thus, in clinical practice, not supposed to influence montelukast SUR2S8-mediated metabolism of certain drugs including paclitaxel, rosiglitazone, repaglinide.
Studies in vitro have shown that montelukast is a substrate of CYP2C8 isoenzymes, and to a lesser extent CYP2C9 isoenzymes and ZA4. These clinical studies of drug interactions in relation to montelukast and gemfibrozil (an inhibitor of CYP2C8 like, and 2C9) demonstrated that the effect of gemfibrozil increases the systemic exposure of montelukast 4.4 times. Joint reception of itraconazole, a strong inhibitor of CYP3A4 isoenzyme, with gemfibrozil and montelukast did not lead to a further increase in the effect of the systemic exposure of montelukast. Effect of gemfibrozil on systemic exposure of montelukast can not be considered clinically significant on grounds of safety when used at doses higher than the approved dose of 10 mg for adults (for example, 200 mg / day for adult patients for 22 weeks, and up to 900 mg / day patients taking the drug for approximately one week, no clinically meaningful adverse effects).
Thus, when co-administered with the dose of montelukast gemfibrozil correction is required. According to studies in vitro, not intended to clinically significant drug-drug interactions with other known inhibitors of CYP2C8 isoenzymes (eg, trimethoprim). In addition, the joint reception of montelukast with itraconazole alone did not lead to a significant increase in the effect of the systemic exposure of montelukast.
Combined treatment with a bronchodilator
drug Montelast is reasonable in addition to bronchodilators alone, if they do not provide adequate control of asthma. Upon reaching the therapeutic effect of the drug treatment can start a gradual reduction in the dose of bronchodilators.
Combination therapy with inhaled corticosteroids
Treatment with Montelast provides additional therapeutic benefit to patients applying inhaled corticosteroids. In stabilization, you can start a gradual reduction in the dose of GCS under medical supervision. In some cases a complete abolition of inhaled corticosteroids, but a sharp substitution of inhaled corticosteroids on Montelast drug is not recommended.
Montelast The drug is not recommended for the treatment of acute asthma attacks. Patients with asthma is recommended to always carry emergency medications. In the event of an acute attack should use an inhaled beta 2 -adrenomimetiki short-acting. Patients should like to consult with your doctor as soon as possible if they need more inhalations of beta 2 -adrenomimetikov short-acting than usual. Do not abruptly replace therapy with inhaled or oral corticosteroids drug Montelast. There is no evidence to prove the possibility of reducing the dose of oral corticosteroids in the background at the same time receiving montelukast.
In rare cases, patients receiving anti-asthma medications, including montelukast may develop systemic eosinophilia, sometimes accompanied by clinical signs of vasculitis, the so-called Chardjui-Strauss syndrome, a condition which is eliminated by receiving systemic corticosteroids. These cases are usually associated with a decrease in dose or cancellation of therapy with oral corticosteroids.
It is impossible to establish or eliminate the likelihood that leukotriene receptor antagonists may be associated with the development-Strauss syndrome Chardjuy. Therefore, doctors should be warned of the possibility of eosinophilia, vaskulyarnoi rash, increase the severity of pulmonary symptoms, cardiac complications and / or neuropathy patients. Patients who develop symptoms testosterone enanthate vs propionate of the above, you must be retested and their treatment regimen to reconsider.
Montelast drug treatment does not lead to the prevention of bronchospasm in patients with hypersensitivity to aspirin, when used acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.
The drug contains lactose monohydrate, and it should not be taken in patients with rare hereditary disorders: galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Effects on ability to drive and use machines
As a general rule, taking montelukast does not affect the ability to drive vehicles or work with other mechanisms, but very rarely, some patients reported drowsiness or dizziness. When you see these symptoms in patients is not recommended to drive and engage in other activities that require concentration and speed of psychomotor reactions. npp steroid