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

Active substanceZafirlukastZafirlukast

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Acolat®

pills inwards

AstraZeneca UK Ltd United Kingdom

Dosage form: & nbspfilm-coated tablets

Composition:

Each tablet contains:

Active substance: zafirlukast 20.0 mg.

Excipients: croscarmellose sodium 12.0 mg, lactose monohydrate 45.0 mg, cellulose microcrystalline 114.0 mg, povidone 7.0 mg, magnesium stearate 2.0 mg; Shell: hypromellose 4.8 mg, titanium dioxide 2.4 mg.

Description:Round, biconvex tablets, covered with a film coating of white or almost white color with the marking "ACCOLATE 20", applied by the embossing method.

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

ATX: & nbsp

R.03.D.C.01 Zafirlukast

Pharmacodynamics:

Synthesis of leukotrienes (LT) 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 increased eosinophilic migration to the lung tissue.

Acolate® is a competitive, highly selective and potent antagonist of peptidic receptors of lecotrienes LTC4, LTD4, LTE4 - components slowly; reacting substance of anaphylaxis.Acolate® acts as an anti-inflammatory agent that reduces the effect of inflammatory mediators.

Acolat® 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.

It was shown that Acolat® 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 airways 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. Acolate® 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 the drug Acolat® at a dose of 20 mg twice a day.

Against the background of long-term use of the drug Acolat®, the long-term improvement in lung function was demonstrated in comparison with the start of treatment even against the background of residual zafirlukast concentration in plasma.

The use of the drug Acolat® in children aged 5 to 11 years (inclusive) at a dose of 10 mg twice a day significantly improves lung function (FEV₁ morning and evening PSV, the frequency of reception of β₂agonists) compared with placebo. This improvement was maintained or increased with 10 mg of Acolat® 2 times a 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 the drug Acolate® allows patients with bronchial asthma to inhale 100 times more leukotriene D4 and provides protection from 12 to 24 hours.

Acolat® 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® alleviates 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 taking Acolat®.

Acolate ® is taken orally and, therefore, can be convenient for admission to patients who have 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%. ТСmax - 3 hours. The value of Css in 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. T_1/2 - 10 h. It is excreted with kidneys by 10%, through the intestine - 89%; partially with breast milk, in the form of metabolites. Zafirlukast not determined in urine.Metabolites, determined in blood plasma, were 90 times less active than zafirlukast in standard in vitro activity tests.

Pharmacokinetics of zafirlukast in adolescents and adults with asthma were similar to the pharmacokinetics in healthy adult males. After correction for body weight, there is no strong difference between the pharmacokinetics of zafirlukast in men and in women.

In elderly patients and patients with alcoholic cirrhosis of the liver, Cmax and AUC is increased by 2 times.

Indications:Prevention of asthma attacks and supporting basic therapy of bronchial asthma.

Contraindications:

Hypersensitivity to Acolat® or its ingredients.

Children under 7 years.

Dysfunction of the liver, including liver cirrhosis.

Galactose intolerance, lactase deficiency or glucose-galactose malabsorption (formulation contains lactose).

Carefully:Elderly patients (over 65 years of age) due to insufficient data on clinical use.

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 at taking the drug exceeds the potential risk to the fetus.

Zafirlukast is excreted in breast milk. Acolate® should not be given to nursing mothers.

Dosing and Administration:

Acolate® is indicated for the prevention of asthma attacks and should therefore be taken for a long time.

Adults and children over 12 years of age

Inside 20 mg twice a day. The usual maintenance dose is also: 20 mg twice a 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 twice a day. The recommended maintenance dose is 10 mg twice daily.

Elderly patients

The zafirlukast clearance in the elderly (over 65 years) is significantly reduced, so that Cmax and AUC are approximately twice as large as in young people.However, the cumulation of zafirlukast in the elderly does not occur in this case. When using the drug Acolat® in elderly patients, at a dose of 20 mg twice a day, there was no increase in the overall incidence of adverse events. Clinical experience with Acolat® in elderly patients (over 65 years of age) is limited, and therefore it is recommended to be cautious when prescribing this medication.

Patients with impaired renal function

Do not require dose adjustment in patients with impaired renal function.

Side effects:

Side effects are classified according to organ systems and development frequency: very often (> 10%), often (from ≥ 1% to <10%), infrequently (from ≥0.1% to <1%), rarely (from ≥0, 01% to <0.1%), very rarely (<0.01%).

The following symptoms were noted during the drug Acolate®.

Are common:

very often - infections

often - weakness

Gastrointestinal system:

often - nausea, vomiting, abdominal pain and other disorders of the gastrointestinal tract.

Liver and biliary tract:

often - increased levels of transaminases

infrequently - hyperbilirubinemia without elevated liver enzymes

rarely symptomatic hepatitis with and without hyperbilirubinemia

very rarely - liver failure, fulminant hepatitis.

Musculoskeletal system:

Often - myalgia

infrequently - arthralgia

Central and peripheral nervous system:

often - a headache

infrequently - insomnia

Skin:

often - a rash

infrequently - itchy skin, hives, swelling

rarely - vesicular rash

The immune system:

infrequently - hypersensitivity reactions
rarely - angioedema

Blood and lymphatic system:

rarely - formation of hematomas with bruises, bleeding, including hypermenorrhea, thrombocytopenia

very rarely - agranulocytosis.

These symptoms usually occurred after discontinuation of therapy. The headache and disturbances from the gastrointestinal tract noted with Acolat® were usually mild and did not require the drug to be discontinued.

There was an increase in the incidence of infections in elderly patients receiving Acolate® (7.8% vs. 1.4%). Infections usually proceeded easily, mainly affecting the respiratory tract and did not require discontinuation of therapy.

Overdose:

There have been isolated reports of cases of overdose of Acolat® in humans.

No significant symptoms were observed.In case of an overdose, supportive therapy should be given. Possible gastric lavage.

Interaction:

Acolat® can be used concomitantly with other types of medication used to treat allergies and bronchial asthma. For example, Acolat® was used concomitantly with inhaled glucocorticosteroids, inhalation and oral therapy with bronchodilators, antibiotics and antihistamines without signs of undesirable interaction. Acolat® can be used concomitantly with oral contraceptives without undesired interaction.

The use of Acolat® concurrently with acetylsalicylic acid ("Aspirin", 650 mg 4 times a day) can lead to an increase in plasma zafirlukast concentration by approximately 45%.

The use of Acolat® concomitantly with erythromycin can lead to a decrease in the concentration of zafirlukast in plasma by about 40%.

In clinical trials, the use of the drug Acolat® concomitantly with theophylline led to a decrease in the concentration of zafirlukast in plasma by about 30% without affecting the plasma concentration of theophylline.However, in post-marketing studies, rare cases of increased theophylline concentration in patients with concomitant use with the drug Acolate® were noted.

The use of the drug Acolat® concurrently with terfenadine leads to a decrease in AUC for zafirlukast by 54%, but without affecting the concentration of terfenadine in plasma.

The use of the drug Acolat® concurrently with warfarin leads to an increase in the maximum prothrombin time by approximately 35%. Therefore, it is recommended that prothrombin time be monitored if Acolate® is used concomitantly with warfarin. Obviously, this interaction is the result of inhibition by the Zafirlukast of the cytochrome P450 2C9 isoenzyme system.

Simultaneous use of the drug Acolat® and fluconazole, a moderate inhibitor of the isoenzyme CYP2C9, resulted in an increase in plasma zafirlukast concentration of approximately 60%. The clinical significance of this interaction is unknown.

Simultaneous use of the drug Acolate® and itraconazole, a potent inhibitor of the isoenzyme CYP3A4, did not cause changes in the zafirlukast concentration in the plasma.

Smoking may increase the zafirlukast's clearance by approximately 20%.

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 Acolat® should be continued during exacerbations of bronchial asthma.

Acolat® does not provide for a reduction in the intake of steroid glucocorticosteroids.

Just like inhaled glucocorticosteroids and disodium cromoglycate and undershot sodium, Acolate ® is not used to stop bronchospasm in acute asthmatic attacks. There should be no abrupt reversal of inhalation or oral glucocorticosteroids when switching to Acolat® therapy.

The use of Acolat® has not been studied in the treatment of intermittent or unstable bronchial asthma.

When taking Acolat®, cases of eosinophilic conditions were noted, including Churg-Strauss syndrome and eosinophilic pneumonia. Manifestations can relate to various organs and systems, including the possible occurrence of vasculitis, impaired lung function, heart complications or neuropathy.At the same time, it was not possible to confirm or reject the causal relationship with the drug Acolat®. When developing an eosinophilic state or Churg-Strauss syndrome, stop taking Acolat®. Subsequently, treatment with Acolate® should not be resumed and Acolat® should be taken to establish a cause-and-effect relationship with evolved eosinophilia.

During therapy with the drug Acolat®, an increase in the level of serum transaminases is possible. Usually these phenomena are of a passing character and occur asymptomatically, but may be early symptoms of hepatotoxicity; and in extremely rare cases are associated with more serious hepatocellular disorders, fulminant hepatitis and hepatic insufficiency. Post-marketing studies had very rare reports of cases of acute liver function disorders that were not preceded by clinical signs 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 research, liver 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 immediate cancellation of the drug can help improve the patient's condition. If liver signs show signs of hepatotoxicity, it should immediately stop taking the drug. Patients in whom Acolate® was discontinued due to the development of hepatotoxicity, the development of which was not associated with any other cause, the re-administration of Acolat® is contraindicated.

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

There is no evidence that Acolat® leads to a deterioration in these activities.

However, when driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions,that with the use of the drug can be observed headache, insomnia.

Form release / dosage:The tablets covered with a film cover of 20 mg.

Packaging:For 14 tablets in a blister of aluminum foil and PVC, 2 blisters in a cardboard pack with instructions for use.

Storage conditions:At temperatures below 30 ° C, in places inaccessible to children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013547 / 01

Date of registration:19.09.2011

Expiration Date:Unlimited

Date of cancellation:2017-01-18

The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom

Manufacturer: & nbsp

ASTRAZENECA UK, Ltd. United Kingdom

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp25.06.2017

Illustrated instructions

Instructions

Acolat® (Accolate)