Akolat

General characteristics. Structure:

Active agent: зафирлукаст 20,0 mg.
Excipients: croscarmellose sodium of 12,0 mg, lactoses monohydrate of 45,0 mg, cellulose of microcrystallic 114,0 mg, povidone of 7,0 mg, magnesium stearate of 2,0 mg; cover: gipromelloza of 4,8 mg, titanium dioxide of 2,4 mg.
Description
Round, biconvex tablets, film coated white or almost white color with marking of "ACCOLATE 20" put with a stamping method.

Pharmacological properties:

Pharmacodynamics. Synthesis of leukotrienes (LT) and their interaction with receptors belongs to links of a pathogeny of the bronchial asthma (which is characterized by existence of inflammatory process) and is shown in reduction of smooth muscles and hypostasis mucous bronchial tubes, change of cellular activity, including increase in level of migration of eosinophils in pulmonary Akolat® fabric - the competitive, high-selection and powerful antagonist of peptide receptors of leukotrienes LTC4, LTD4, LTE4 - components of slowly reacting anaphylaxis substance. Аколат® works as the antiinflammatory agent reducing effect of mediators of an inflammation.
Аколат® to the same extent prevents the bronchospasm caused by all three peptide leukotrienes (C4, D4 and E4 leukotrienes).
Researches on animals showed that Akolat® effectively prevents the increase in permeability of vessels caused by leukotrienes leading to hypostasis, and the increase in level of eosinophils caused by leukotrienes in pulmonary fabric.
It is shown that Akolat® interacts only with receptors of leukotrienes and does not affect prostaglandinovy, tromboksanovy, cholinergic and histamine receptors.
Аколат® reduces cellular and noncellular components of the inflammation in pneumatic ways caused by antigenic provocation with the subsequent bronchial lavage in 48 hours, зафирлукаст reduces rise in level of basophiles, lymphocytes and a histamine, and reduces stimulated products of superoxides alveolar macrophages. Аколат® weakened the bronchial hyperreactivity increasing after provocation by inhalation allergens and the bronkhokonstriktion induced by the factor activating thrombocytes. Further sensitivity to metasincaline decreased at long administration of drug of Akolat® in a dose of 20 mg twice a day.
Against the background of long administration of drug of Akolat® long improvement of indicators of function of lungs in comparison with an initiation of treatment even against the background of residual concentration of a zafirlukast in plasma was shown.
Use of the drug Akolat® for children aged from 5 up to 11 years (inclusive) in a dose on 10 mg 2 times a day significantly improves function of lungs (OFV1 morning and evening PSV, reception frequency β2-агонистов) in comparison with placebo. This improvement remained or increased at reception of 10 mg of the drug Аколат® 2 of time a day during 1 year.
The dozozavisimy inhibition of the bronkhokonstriktion caused by the inhalated D4 leukotriene is established. The patients having bronchial asthma are about 10 times more sensitive to the bronkhokonstriktion caused by the inhalated D4 leukotriene. One-time administration of drug of Akolat® allows patients to inhalate with bronchial asthma in 100 times more of D4 leukotriene and provides protection from 12 to 24 hours.
Аколат® inhibits the bronkhokonstriktion caused by several types of provocations, for example, sulfurdioksidy, an exercise stress, cold air. Аколат® weakens early and late phases of the inflammatory reactions caused by various antigens, such as plants, dandruff of animals, an ambrosia and the mixed antigens.
Аколат® facilitates symptoms of bronchial asthma (reduces day and night symptoms of bronchial asthma), improves function of lungs, reduces the need for reception of beta-adrenergic agonists and reduces the frequency of exacerbations of a disease.
Initial improvement of symptoms of bronchial asthma arises within the first weeks, and sometimes and the first days of administration of drug of Akolat®.
Аколат® is accepted inside and, therefore, it can be convenient for reception to patients who experience difficulties using medicines in the form of aerosols.

Pharmacokinetics. After intake it is soaked up quickly, but it is insufficiently full, meal fat-rich or protein reduces bioavailability by 40%. TСmax-3 of hour. The size Css in plasma is proportional to a dose and it is predicted on pharmacokinetics of a single dose. Communication with proteins (albumine) - 99%. Cumulation – low.
It is extensively metabolized in a liver with formation of inactive metabolites. T1/2 - 10 h. It is brought with kidneys to 10%, through intestines - 89%; partially with breast milk, in the form of metabolites. Зафирлукаст is not defined in urine. The metabolites defined in a blood plasma by 90 times were less active, than зафирлукаст in standard tests of activity in vitro.
The teenagers and adults having asthma had a similar to pharmacokinetics pharmacokinetics of a zafirlukast at healthy adult men. After correction on body weight strong differences between pharmacokinetics of a zafirlukast at men and at women are not observed. At patients of advanced age and at patients with alcoholic cirrhosis, Cmax and AUC increases twice.

Indications to use:

Prevention of attacks of bronchial asthma and the supporting basic therapy of bronchial asthma.

Route of administration and doses:

Аколат® it is shown for prevention of attacks of bronchial asthma and therefore has to be accepted it is long.
Adults and children are more senior than 12 years
In 20 mg two times a day. The usual maintenance dose also makes: 20 mg two times a day. It is not necessary to exceed the recommended dose. Reception of higher dose of drug can be connected with increase in level of one or more liver enzymes and development of a hepatotoxic.
Аколат® should not be accepted along with food as food reduces bioavailability of a zafirlukast.
Children from 7 to 11 years (inclusive)
It is recommended to begin treatment with a dose of 10 mg two times a day. The recommended maintenance dose makes 10 mg two times a day.
Elderly patients
The clearance of a zafirlukast at elderly (65 years are more senior) is considerably reduced so Cmax and AUC are approximately twice more, than at young people. However, cumulation of a zafirlukast at elderly people at the same time does not happen. At use of the drug Akolat® for elderly patients, in a dose of 20 mg twice a day, increase in the general frequency of the adverse phenomena was not observed. Clinical experience of use of Akolata® for elderly patients (65 years are more senior) is limited in this connection this group of patients is recommended to show care at purpose of drug.
Patients with renal failures
Dose adjustment is not required from patients with renal failures.

Features of use:

To gain effect of treatment, Akolat® needs to accept regularly even if symptoms of bronchial asthma do not disturb. As a rule, therapy by the drug Akolat® should be continued during exacerbations of bronchial asthma.
Administration of drug of Akolat® does not provide reduction of reception of steroid glyukokortikosteriod.
The same as and dinatrium кромогликат also nedokromit inhalation glucocorticosteroids sodium, Akolat® is not used for stopping of a bronchospasm at bad asthmatic attacks.
Sharp cancellation of inhalation or peroral glucocorticosteroids upon transition to therapy should not be the drug Akolat®.
Use of the drug Akolat® was not studied at treatment of intermittent or unstable bronchial asthma.
At administration of drug of Akolat® noted cases of development of eosinophilic states, including a syndrome of Churg-Strauss and eosinophilic pneumonia. Manifestations can concern various bodies and systems, including emergence of a vasculitis, deterioration in function of lungs, cordial complications or a neuropathy is possible. At the same time it was not succeeded to confirm or reject relationship of cause and effect with administration of drug of Akolat®. At development of an eosinophilic state or syndrome of Churg-Strauss it is necessary to stop administration of drug of Akolat®. Afterwards it is not necessary to resume treatment by the drug Akolat® and to accept Akolat® for the purpose of establishment of relationship of cause and effect with the developed eosinophilia.
During therapy by the drug Akolat® increase in level of transaminases of blood serum is possible. Usually these phenomena have the passing character and proceed asymptomatically, but can be also early symptoms of a hepatotoxic, and in extremely exceptional cases are associated with more serious hepatocellular violations, the fulminant course of hepatitis and a liver failure. During the post-market researches there were very rare messages on cases of acute disorders of function of a liver to which clinical symptoms or symptoms of dysfunction did not precede.
In case of the clinical signs or symptoms indicating liver dysfunction (for example, anorexia, nausea, vomiting, pain in the right upper quadrant of a stomach, increased fatigue, slackness, apathy, grippopodobny symptoms, increase in a liver, an itch and jaundice), administration of drug should be cancelled. It is recommended to determine immediately the level of serumal transaminases, in particular serum ALT. Doctors can consider the values received during the routine researches of liver enzymes. Periodic control of level of serumal transaminases does not prevent emergence of serious hepatic violations, but the early detection of abnormal liver functions caused by administration of drug along with immediate drug withdrawal can promote improvement of a condition of the patient. If during researches of function of a liver hepatotoxic signs are revealed, it is necessary to stop administration of drug immediately. Repeated purpose of the drug Akolat® is contraindicated to patients at whom Akolat® was cancelled because of development of a hepatotoxic which development was not connected with any other reason.
INFLUENCE ON ABILITY TO DRIVE THE CAR AND OTHER MECHANISMS
There are no data that Akolat® leads to deterioration in these types of activity.
However, during the driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions it is necessary to consider that at use of drug the headache, sleeplessness can be observed.

Side effects:

Side effects are classified by systems of bodies and frequency of development: very often (> 10%), it is frequent (from ≥1% to <10%), infrequently (from ≥0,1% to <1%), is rare (from ≥0,01% to <0,1%), is very rare (<0,01%).
Below the listed symptoms were noted during administration of drug of Akolat®.
The general:
very often - infections
often - weakness
Gastrointestinal system:
often - nausea, vomiting, abdominal pains and other disturbances from digestive tract
Liver and biliary tract:
often - increase in level of transaminases
infrequently - a hyperbilirubinemia without the increased content of liver enzymes
seldom - symptomatic hepatitis with and without hyperbilirubinemia
very seldom - a liver failure, the fulminantny hepatitis Musculoskeletal system:
often - a mialgiya
infrequently - an arthralgia
Central and peripheral nervous system:
often - a headache
infrequently - sleeplessness
Integuments:
often – rash
infrequently - a skin itch, a small tortoiseshell, hypostasis
seldom – vesicular rash
Immune system:
infrequently - hypersensitivity reactions
seldom – a Quincke's disease
Blood and lymphatic system:
seldom – formation of hematomas at bruises, bleedings, including a hypermenorrhea, thrombocytopenia
very seldom – an agranulocytosis
The specified symptoms usually passed after the therapy termination. The headaches and disturbances noted at administration of drug by Akolat® from digestive tract usually had moderate character and did not demand drug withdrawal.
Increase in frequency of infections at the elderly patients receiving Akolat® was observed (7,8% against 1,4%). Infections usually proceeded easily, preferential affected a respiratory path and did not demand the therapy termination.

Interaction with other medicines:

Аколат® it can be applied along with other types of the medicamentous therapy applied to treatment of an allergy and bronchial asthma. For example, Akolat® was applied along with inhalation glucocorticosteroids, inhalation and peroral therapy by bronkhodilyatator, antibiotics and antihistaminic drugs without signs of undesirable interaction.
Аколат® it can be applied along with oral contraceptives without undesirable interaction.
Administration of drug of Akolat® along with acetylsalicylic acid ("Aspirin", 650 mg 4 times a day) can lead to increase in level of a zafirlukast in plasma approximately for 45%.
Administration of drug of Akolat® along with erythromycin can lead to decrease in level of a zafirlukast in plasma approximately for 40%.
In clinical trials administration of drug of Akolat® along with theophylline led to decrease in level of a zafirlukast in plasma approximately for 30% without influence on the plasma level of theophylline. However during the post-market researches, exceptional cases of increase at patients of level of theophylline at its concomitant use with the drug Akolat® were celebrated.
Administration of drug of Akolat® along with terfenadiny leads to reduction of AUC for a zafirlukast for 54%, but without influence on the level of a terfenadin in plasma.
Administration of drug of Akolat® along with warfarin leads to increase in the maximum prothrombin time approximately for 35%. Therefore it is recommended to control a prothrombin time if Akolat® is applied along with warfarin. Obviously, this interaction is result of inhibition zafirlukasty isofermental system of P450 2C9 cytochrome.
At smokers increase in clearance of a zafirlukast approximately by 20% is possible.

Contraindications:

Hypersensitivity to the drug Akolat® or its ingredients.
Children's age up to 7 years.
Abnormal liver functions, including cirrhosis.
Intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malabsorption (drug contains lactose).
WITH CARE
Elderly patients (65 years are more senior) in communication by insufficiency of data on a clinical use.
PREGNANCY AND LACTATION
Safety of administration of drug of Akolat® by women during pregnancy is not established. Use of drug during pregnancy is possible only in that case when the estimated advantage for mother at administration of drug exceeds potential risk for a fruit.
Зафирлукаст it is excreted with breast milk. Аколат® it should not be appointed to nursing mothers.

Overdose:

People had separate messages on cases of overdose of the drug Akolat®. No essential symptoms were observed. In case of overdose it is necessary to carry out a maintenance therapy. The gastric lavage is possible.

Storage conditions:

At a temperature below 30 °C, in the places unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 20 mg. On 14 tablets in the blister from aluminum foil and PVC, on 2 blisters in a cardboard pack with the application instruction.