Composition, form of production and packaging
The tablets covered with a cover of white or almost white color, round, biconcave, with engraving "ACCOLATE 20" on one side.
1 tab.
zafirlukast 20 mg
Excipients: sodium croscarmellose, lactose monohydrate, microcrystalline cellulose, povidone, magnesium stearate, hypromellose, titanium dioxide.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
The blocker of leukotriene receptors. Synthesis of leukotrienes and their interaction with receptors refers to the links of the pathogenesis of bronchial asthma (characterized by the presence of an inflammatory process) and manifests itself in the reduction of smooth muscles and edema of bronchial mucosa, changes in cellular activity, including an increase in the level of eosinophil migration into the lung tissue.
Zafirlukast is a competitive, highly selective and potent antagonist of peptidic receptors of lecotrienes LTC4, LTD4, LTE4 - components of the slow reacting substance of anaphylaxis. Zafirlukast acts as an anti-inflammatory agent, which reduces the effect of inflammatory mediators.
Zafirlukast equally prevents bronchospasm caused by all three peptidic leukotrienes (leukotrienes C4, D4 and E4).
Animal studies have shown that Acolate effectively prevents leukotriene-induced increases in vascular permeability leading to edema and leukotriene-induced increases in the level of eosinophils in the lung tissue.
The specificity of Acolate was proven in clinical studies, where it was shown that Acolate interacts only with leukotriene receptors and does not affect prostaglandin, thromboxane, cholinergic and histamine receptors.
Acolate reduces the cellular and noncellular components of inflammation in the airway caused by antigenic provocation, followed by bronchial lavage after 48 hours;zafirlukast reduces the rise in the level of basophils, lymphocytes and histamine, and reduces the stimulated production of superoxide alveolar macrophages. Akolat weakened the bronchial hyperreactivity and bronchoconstriction, induced by the platelet activating factor, which increased after inhalation allergens provocation.Subsequently, the sensitivity to methacholine decreased with prolonged use of Acolate in a dose of 20 mg 2 times / day.
In clinical trials with long-term use of Acolate, the long-term improvement in pulmonary function was demonstrated compared with the start of treatment, even with the residual concentration of zafirlukast in plasma.
Studies in children 5-11 years of age (inclusive) showed that the use of Acolate 10 mg twice daily significantly improves lung function (FEV 1 morning and evening PSV, the frequency of taking 2- agonists) compared with placebo. This improvement persisted or increased with the admission of Acolate 10 mg 2 times / day for 1 year.
A dose-dependent inhibition of bronchoconstriction caused by inhaled leukotriene D4 was established. Patients suffering from bronchial asthma are approximately 10 times more sensitive to bronchoconstriction caused by inhaled leukotriene D4. A single dose of Acolate allows patients with bronchial asthma to inhale 100 times more leukotriene D4 and provides protection from 12 to 24 hours.
Acolate inhibits bronchoconstriction caused by several kinds of provocations, for example, sulfurous oxide, physical exertion, cold air. Acolate weakens the early and late phases of inflammatory reactions caused by various antigens, such as plants, animal dander, ambrosia and mixed antigens.
Acolate facilitates the symptoms of bronchial asthma (reduces day and night symptoms of bronchial asthma), improves lung function, reduces the need for beta-adrenomimetics and reduces the frequency of exacerbations of the disease.
The initial improvement in the symptoms of bronchial asthma occurs during the first weeks, and sometimes the first days of Acolat's administration.
Acolate is intended for oral administration and, therefore, is convenient for patients who experience difficulties with the use of drugs in the form of aerosols.
PHARMACOKINETICS
After intake, absorbed quickly, but not fully enough, eating high in fat or protein reduces bioavailability by 40%. The time to reach C max is 3 hours. The value of C ssin the plasma is proportional to the dose and is predicted from the pharmacokinetics of a single dose. The connection with proteins (albumin) is 99%. Cumulation is low.
Extensively metabolized in the liver with the formation of inactive metabolites. Рў 1/2 - 10 С‡. It is deduced with kidneys on 10%, through an intestine - 89%; in part - with breast milk in the form of metabolites. Zafirlukast is not defined in the urine. Metabolites determined in blood plasma were 90 times less active than zafirlukast in standard in vitro activity tests.
The pharmacokinetics of zafirlukast in adolescents and adults suffering from asthma were similar to pharmacokinetics in healthy adult men. After correction for body weight, there is no strong difference between the pharmacokinetics of zafirlukast in men and in women.
In elderly patients and in individuals with alcoholic cirrhosis of the liver, C max and AUC increase 2-fold.
INDICATIONS
- prophylaxis of attacks of bronchial asthma;
- supporting basic therapy of bronchial asthma.
DOSING MODE
Acolate is indicated for the prevention of bronchial asthma attacks and therefore should be taken for a long time.
Adults and children over 12 years of age
Inside 20 mg 2 times / day. The usual maintenance dose is also 20 mg 2 times / day. Do not exceed the recommended dose. The administration of a higher dose of the drug may be associated with an increase in the level of one or more hepatic enzymes and the development of hepatotoxicity.
Acolate should not be taken concomitantly with food, since food reduces the bioavailability of zafirlukast.
Children from 7 to 11 years (inclusive)
It is recommended to begin treatment with a dose of 10 mg 2 times / day. The recommended maintenance dose is 10 mg 2 times / day.
Elderly
Clearance zafirlukasta in the elderly (over 65 years) is significantly reduced. C max and AUC are approximately 2 times greater than in young people. However, the cumulation of zafirlukast in the elderly does not occur. In clinical studies in elderly patients who received Acolat 20 mg 2 times / day, there was no increase in the overall incidence of adverse events. Clinical experience of Acolat in elderly patients (over 65 years) is limited, and therefore it is recommended to be cautious when prescribing this group of patients.
Renal impairment
Do not require dose adjustment in patients with impaired renal function.
Dysfunction of the liver
Clear zafirlukasta lowered in patients with alcoholic cirrhosis, so that Cmax and AUC approximately 2 times greater than in healthy. Therapy can begin with taking 20 mg 2 times / day and adjust the dose depending on the clinical response. There were no clinical studies using Acolate in patients with hepatitis. There is also no evidence of prolonged use of Acolate in patients with cirrhosis.
It is recommended to monitor prothrombin time while taking with warfarin.
SIDE EFFECT
From the digestive tract: nausea, vomiting, abdominal pain (often).
From the liver and bile ducts: symptomatic hepatitis with and without hyperbilirubinemia (rare), hyperbilirubiaemia without elevated liver enzymes (rare), liver failure (very rarely), fulminant hepatitis (very rarely).
From the musculoskeletal system: arthralgia, myalgia (rarely).
On the part of the skin: a rash, including vesicular rash, itchy skin, hypersensitivity reactions, including urticaria and angioedema (rarely), swelling (not often).
From the side of the central nervous system: insomnia, headache (often).
From the hematological system: the formation of hematomas with bruises (rare), bleeding, including hypermorrhoea (rare), thrombocytopenia (rarely) and agranulocytosis (very rarely).
On the part of the body as a whole: weakness (often).
These symptoms usually occurred after discontinuation of therapy. The headache and abnormalities noted by Acolat were usually moderate and did not require discontinuation of the drug.
There was an increase in the incidence of infections in elderly patients who received Acolat (7.8% vs. 1.4%). Infections usually flowed easily, mainly affecting the respiratory tract and did not require discontinuation of therapy.
CONTRAINDICATIONS
- children's age till 7 years;
- Hypersensitivity to zafirlukastu or other ingredients of the drug.
Acolate is not recommended for patients who have liver function abnormalities, incl. patients with cirrhosis of the liver.
PREGNANCY AND LACTATION
The safety of Acolat in women during pregnancy is not established. The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.
Zafirlukast is excreted in breast milk, Acolat should not be given to nursing mothers.
APPLICATION FOR FUNCTIONS OF THE LIVER
Do not require dose adjustment in patients with impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Clear zafirlukasta lowered in patients with alcoholic cirrhosis, so that Cmax and AUC approximately 2 times greater than in healthy. Therapy can begin with taking 20 mg 2 times / day and adjust the dose depending on the clinical response. There were no clinical studies using Acolate in patients with hepatitis. There is also no evidence of prolonged use of Acolate in patients with cirrhosis.
APPLICATION FOR CHILDREN
The use of Acolate is contraindicated in children under 7 years of age.
Children from 7 to 11 years (inclusive): it is recommended to start treatment with a dose of 10 mg 2 times / day. The recommended maintenance dose is 10 mg 2 times / day.
APPLICATION IN ELDERLY PATIENTS
Clearance zafirlukasta in the elderly (over 65 years) is significantly reduced; C max and AUC are approximately 2 times greater than in young people. However, the cumulation of zafirlukast in the elderly does not occur. In clinical studies in elderly patients who received Acolalt 20 mg 2 times / day, there was no increase in the overall incidence of adverse events. Clinical experience of Acolat in elderly patients (over 65 years) is limited, and therefore it is recommended to be cautious when prescribing this group of patients.
SPECIAL INSTRUCTIONS
To obtain the effect of treatment, Acolate must be taken regularly, even if the symptoms of bronchial asthma are not disturbed. As a rule, therapy with Acolatum should be continued during exacerbations of bronchial asthma.
Just like inhaled glucocorticosteroids, disodium cromoglycate and nedocromil sodium, Acolate is not used to stop bronchospasm in acute asthmatic attacks.
Avoid abrupt discontinuation of inhaled or oral glucocorticosteroids when switching to Acolate therapy.
The use of Acolate has not been studied in the treatment of intermittent or unstable bronchial asthma.
With the reception of Acolat, there were cases of development of eosinophilic conditions, including Churg-Strauss syndrome and eosinophilic pneumonia.Manifestations can relate to various organs and systems, incl. possibly the appearance of vasculitis, worsening lung function, heart complications or neuropathy. At the same time, it was not possible to confirm or reject the cause-and-effect relationship with the reception of Akolat. With the development of eosinophilic state or Churg-Strauss syndrome, Acolat should be discontinued. Subsequently, the treatment with Acolatum should not be resumed and Acolat taken with the aim of establishing a causal relationship with the developed zosinophilia.
During the treatment with Acolate, an increase in the level of serum transaminases is possible. Usually these phenomena are of a passing nature and are asymptomatic, but may be early symptoms of hepatotoxicity, and in very rare cases are associated with more serious hepatocellular disorders, fulminant hepatitis and hepatic insufficiency. In the postmarketing studies, there were very few reports of cases of acute liver function disorders that were not preceded by clinical symptoms or signs of dysfunction.
In case of clinical signs or symptoms indicating liver dysfunction (eg, anorexia, nausea, vomiting, pain in the upper right quadrant of the abdomen, fatigue, lethargy, apathy, flu-like symptoms, enlargement of the liver, pruritus and jaundice), the drug should be withdrawn . It is recommended to immediately determine the level of serum transaminases, in particular ALT of serum. Doctors can take into account the values ​​obtained during routine studies of hepatic enzymes. Periodic monitoring of serum transaminase levels does not prevent the occurrence of serious hepatic impairment, but timely detection of liver function abnormalities caused by taking the drug, along with the immediate cancellation of the drug can help improve the patient's condition. If liver signs show signs of hepatotoxicity, stop taking the drug immediately. Patients in whom Acolat was canceled due to the development of hepatotoxicity, the development of which was not associated with any other cause, the re-administration of Acolat is contraindicated.
Impact on the ability to drive vehicles and manage mechanisms
There is no information that Acolat leads to the deterioration of these activities.
OVERDOSE
There were separate reports of cases of overdose of Acolate in humans.
In case of an overdose, supportive therapy should be given. Possible gastric lavage.
DRUG INTERACTION
Acolate can be used concomitantly with other types of medication used to treat allergies and bronchial asthma. For example, Acolate was used concomitantly with inhaled glucocorticosteroids, inhalation and oral therapy with bronchodilators, antibiotics and antihistamines without signs of undesirable interaction.
Acolate can be used concomitantly with oral contraceptives without undesirable interaction.
Taking Acolat simultaneously with acetylsalicylic acid (650 mg 4 times / day) can lead to an increase in the level of zafirlukast in plasma by approximately 45%.
Taking Acolate simultaneously with erythromycin can lead to a decrease in the level of zafirlukast in plasma by about 40%.
In clinical trials, the administration of Acolat simultaneously with theophylline led to a decrease in the level of zafirlukast in plasma by about 30% without affecting the plasma level of theophylline. However, during postmarketing studies, rare cases of a rise in the level of theophylline in patients with simultaneous admission with Acolate were noted.
Admission of Acolate simultaneously with terfenadine leads to a decrease in AUC for zafirlukast by 54%, but without affecting the level of terfenadine in plasma.
Admission of Acolate simultaneously with warfarin leads to an increase in the maximum prothrombin time by approximately 35%. Therefore, it is recommended to monitor prothrombin time in the event that Acol is applied simultaneously with warfarin. Obviously, this interaction is the result of the inhibition of the cytochrome P450 2C9 isoenzyme system by zafirlukast.
Smoking may increase the zafirlukast's clearance by approximately 20%.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. Store at temperatures below 30 В° C in places inaccessible to children.
Shelf life - 3 years.
