КардиАСК®

General characteristics. Structure:

Active agents: acetylsalicylic acid of 50 mg and 100 mg;
excipients: stearic acid, starch corn, lactoses monohydrate (sugar milk), the castor oil hydrogenated povidone (пласдон K-90 or коллидон 90 F), polysorbate (twin-80), cellulose microcrystallic;
excipients for receiving a film kishechnorastvorimy cover: methacrylic acid and ethyl acrylate copolymer (1:1) (kollinut MAY 100P), a macrogoal and polyvinyl alcohol copolymer (kollinut IR), коповидон (пласдон Es-630), triethyl citrate, talc, titanium dioxide.

Description: tablets, film coated white or almost white color, round, biconvex. The easy roughness and a slight smell of acetic acid is allowed.

Pharmacological properties:

Pharmacodynamics. Irreversible inhibition of cyclooxygenase (TsOG-1) therefore synthesis of A2 thromboxane is blocked is the cornerstone of the mechanism of antiagregantny effect of acetylsalicylic acid (ASK) and aggregation of thrombocytes is suppressed. The Antiagregantny effect develops even after use of small doses of drug and remains within 7 days after a single dose. It is considered that ASK has also other mechanisms of suppression of aggregation of thrombocytes that broadens area of its use at various vascular diseases. In high doses of ASK also has antiinflammatory, febrifugal and analgeziruyushchy effect.

Pharmacokinetics. After intake of ASK it is quickly and completely soaked up from the digestive tract (DT). ASK is partially metabolized during absorption. In time and after absorption of ASK turns into the main metabolite – salicylic acid which is metabolized, mainly, in a liver under the influence of enzymes with formation of such metabolites as salol, salicylic acid a glucuronide and salitsilurovy acid, found in many fabrics and in urine. At women process of metabolism takes place more slowly (smaller activity of enzymes in blood serum). The maximum concentration of ASK in a blood plasma is reached in 10-20 minutes after intake, salicylic acid – in 0,3-2 hours.
Because tablets are covered with an acid resisting cover, ASK is released not in a stomach (the cover effectively blocks dissolution of drug in a stomach), and in the alkaline environment of a duodenum. Thus, absorption of ASK in the form of the tablets covered with a kishechnorastvorimy cover is slowed down for 3-6 hours in comparison with usual (without such cover) tablets.
ASK and salicylic acid contact proteins of a blood plasma (from 66% to 98% depending on a dose) and are quickly distributed in an organism. Salicylic acid gets through a placenta and into breast milk.
Removal of salicylic acid is dozozavisimy as her metabolism is limited by opportunities of enzymatic system. The elimination half-life makes of 2-3 o'clock at use of ASK in low doses and till 15 o'clock at use of drug in high doses (usual doses of acetylsalicylic acid as analgeziruyushchy means). Unlike other salicylates, at multiple dose of drug not hydrolyzed ASK does not collect in blood serum. Salicylic acid and its metabolites are removed by kidneys. At patients with normal function of kidneys of 80-100% of a single dose of drug it is removed by kidneys within 24-72 hour.

Indications to use:

- Primary prevention of an acute myocardial infarction with risk factors (for example, a diabetes mellitus, a lipidemia, arterial hypertension, obesity, smoking, advanced age) and a repeated myocardial infarction.
- Unstable stenocardia (including suspicion on development of an acute myocardial infarction) and stable stenocardia.
- Prevention of an ischemic stroke (including at patients with passing disturbance of cerebral circulation).
- Prevention of a thromboembolism after operations and invasive interventions on vessels (for example, aortocoronary shunting, endarterectomy of carotid arteries, arteriovenous shunting, angioplasty and stenting of coronary arteries, angioplasty of carotid arteries).
- Prevention of a deep vein thrombosis and thromboembolism of a pulmonary artery and its branches (including, at a long immobilization as a result of extensive surgical intervention).

Route of administration and doses:

It is desirable to take a pill of the drug Kardiask® before food, washing down with a large amount of liquid. The pill Kardiask® is taken 1 time a day. КардиАСК® it is intended for prolonged use. Duration of therapy is defined by the doctor.
Primary prevention of an acute myocardial infarction with risk factors: 50 - 100 mg/days.
Prevention of a repeated myocardial infarction, stable and unstable stenocardia: 50 - 100 mg/days.

Unstable stenocardia (at suspicion on development of an acute myocardial infarction): 50 - 100 mg/days.
Prevention of an ischemic stroke and passing disturbance of cerebral circulation: 50 - 100 mg/days.
Prevention of a thromboembolism after operations and invasive interventions on vessels: 50 - 100 mg/days.
Prevention of a deep vein thrombosis and thromboembolism of a pulmonary artery and its branches: 50 - 100 mg/days.

Features of use:

ASK can provoke a bronchospasm, and also cause attacks of bronchial asthma and other hypersensitivity reactions. Risk factors are existence of bronchial asthma in the anamnesis, hay fever, the polypose of a nose, chronic diseases of respiratory system, and also allergic reactions to other drugs (for example, skin reactions, an itch, urticaria).
The inhibiting effect of ASK on aggregation of thrombocytes remains within several days after reception in this connection, increase in risk of bleedings is possible during an operative measure or in the postoperative period. In need of an absolute exception of bleeding during an operative measure it is necessary to refuse whenever possible completely use of ASK in the preoperative period.
Acetylsalicylic acid in low doses can provoke development of gout in the predisposed persons (having reduced excretion of uric acid).
High doses of acetylsalicylic acid render hypoglycemic effect that patients need to mean at appointment it with the diabetes mellitus receiving hypoglycemic drugs.
At the combined use of GKS and salicylates it is necessary to remember that during treatment concentration of salicylates in blood is reduced, and after cancellation of GKS the overdose of salicylates is possible.
Exceeding of a dose of acetylsalicylic acid is accompanied by risk of gastrointestinal bleeding.

Side effects:

From the alimentary system: nausea, heartburn, vomiting, abdominal pains are most often noted; seldom – ulcers of a mucous membrane of a stomach and a duodenum; very seldom – ruptured ulcers of a mucous membrane of a stomach and duodenum, gastrointestinal bleedings, passing abnormal liver functions with increase in activity of "hepatic" transaminases.
From system of a hemopoiesis: purpose of ASK is followed by the increased risk of bleedings owing to an inhibiting effect of ASK on aggregation of thrombocytes, is rare - anemia.
Allergic reactions: skin rash, a skin itch, a small tortoiseshell, a Quincke's edema, rhinitis, a rhinedema, rhinitis, a cardiorespiratory distress syndrome, and also heavy reactions, including an acute anaphylaxis.
From the central nervous system: dizziness, decrease in hearing, headache, sonitus.

Interaction with other medicines:

КардиАСК® at simultaneous use strengthens effect of the following medicines:
- a methotrexate due to decrease in renal clearance and its replacement from communication with proteins of plasma, also the combination of acetylsalicylic acid to a methotrexate is followed by the increased frequency of development of side effects from bodies of a hemopoiesis;
- heparin and indirect anticoagulants due to dysfunction of thrombocytes and replacement of indirect anticoagulants from communication with proteins of plasma;
- thrombolytic and antiagregant (tiklopidin);
- digoxin owing to decrease in its renal excretion;
- hypoglycemic means (insulin and derivatives of sulphonylurea) due to hypoglycemic properties of the most acetylsalicylic acid in high doses and replacement of derivatives of sulphonylurea from communication with proteins of plasma;
- valproic acid due to its replacement from communication with proteins of plasma.

The combination of acetylsalicylic acid to anticoagulants, trombolitika and antiagregant is followed by the increased risk of development of bleeding.
At a concomitant use of acetylsalicylic acid with alcohol the additive effect is observed and the risk of injury of a mucous membrane of digestive tract and lengthening of a bleeding time increases.

ASK weakens effect of uricosuric drugs - a benzbromaron (decrease in uricosuric effect owing to competitive suppression of renal canalicular excretion of uric acid), inhibitors of an angiotensin-converting enzyme (APF) (dozozavisimy reduction in the rate of glomerular filtering as a result of inhibition of prostaglandins possessing vasodilating action, respectively weakening of hypotensive action is noted), diuretics (at combined use with ASK in high doses reduction in the rate of glomerular filtering as a result of decrease in synthesis of prostaglandins in kidneys is noted).
Strengthening elimination of salicylates, system glucocorticosteroids (GKS) weaken their action.

Contraindications:

- Hypersensitivity to acetylsalicylic acid, excipients as a part of drug and to other non-steroidal anti-inflammatory drugs (NPVP).
- The bronchial asthma induced by reception of salicylates and other NPVP; a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms, intolerance of ASK and other NPVP.
- Digestive tract erosive cankers (in an aggravation stage).
- Gastrointestinal bleeding.
- Hemorrhagic diathesis.
- The combined use with a methotrexate in a dose of 15 mg a week and more.
- Pregnancy (I and III trimester) and lactation period.
- Children's age up to 18 years.
- The expressed renal failure (the clearance of creatinine (CC) less than 30 ml/min.).
- The expressed liver failure (a class B above on a scale of Chayld-Pyyu).
- Chronic heart failure (the III-IV functional class on NYHA classification).
- Deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

With care:
- At gout, a hyperuricemia since ASK in low doses reduces excretion of uric acid; it must be kept in mind that ASK in low doses can provoke development of gout in the predisposed patients (having reduced excretion of uric acid).
- In the presence in the anamnesis of cankers of digestive tract or gastrointestinal bleedings.
- At an abnormal liver function (below a class B on a scale of Chayld-Pyyu).
- At a renal failure (KK more than 30 ml/min.).
- At bronchial asthma, chronic diseases of a respiratory organs, hay fever, a polypose of a nose, a medicinal allergy, including the NPVP group (analgetics, anti-inflammatory, antirheumatic drugs).
- In the II trimester of pregnancy.
- At estimated surgical intervention (including insignificant, for example, extraction of tooth) as ASK can cause tendency to development of bleedings within several days after administration of drug.

Use at pregnancy and a lactation:
Use of high doses of salicylates in the first 3 months of pregnancy is associated with the increased frequency of defects of fetation (the split sky, heart diseases). Purpose of salicylates in the I trimester of pregnancy is contraindicated. In the II trimester of pregnancy it is possible to appoint salicylates only taking into account strict assessment of risk for a fruit and advantage for mother, not higher than 150 mg/days are preferable in doses and it is short.
In the last trimester of pregnancy salicylates in a high dose (more than 300 mg/days) cause weakening of patrimonial activity, premature closing of an arterial channel in a fruit, the raised bleeding in mother and a fruit, and appointment just before childbirth can cause intracraneal hemorrhages, especially in premature children. Purpose of salicylates in the last trimester of pregnancy is contraindicated.
Salicylates and their metabolites in small amounts get into breast milk. Accidental reception of salicylates in the period of a lactation is not followed by development of side reactions in the child and does not demand the breastfeeding termination. However at prolonged use of drug or appointment it in a high dose feeding by a breast should be stopped immediately.

Overdose:

Salitsilatny intoxication (develops at reception of ASK in a dose more than 100 mg/kg/days on an extent of more than 2 days) can be result of the long use of toxic doses of drug within the wrong therapeutic use of drug (chronic intoxication) or single accidental or intended dose of a toxic dose of drug by the adult or child (acute intoxication).
Symptoms of chronic intoxication derivatives of salicylic acid are not specific and are often diagnosed hardly. Intoxication of easy severity usually develops only after numerous use of high doses of drug and is shown by the dizziness, a sonitus, decrease in hearing increased by sweating, nausea and vomiting, a headache and confusion of consciousness. The specified symptomatology disappears after reduction of a dose of drug. The sonitus can appear at concentration of ASK in a blood plasma from 150 to 300 mkg/ml. Heavier symptoms are shown at concentration of ASK in a blood plasma higher than 300 mkg/ml.
The main display of acute intoxication is heavy disturbance of an acid-base state which manifestations can vary depending on age of the patient and severity of intoxication. At children the most typical is development of a metabolic acidosis. Treatment of intoxication is carried out according to the accepted standards and depends on severity of intoxication and a clinical picture and has to be directed mainly to acceleration of removal of drug and recovery of water and electrolytic balance and an acid-base state.
The overdose is especially dangerous at patients of advanced age.

Overdose symptoms from easy to moderate severity:
Dizziness, sonitus, deterioration in hearing, the increased sweating, nausea, vomiting, headache, confusion of consciousness, profuse sweating, tachypnea, hyperventilation, respiratory alkalosis.
Treatment: gastric lavage, multiple dose of absorbent carbon, the forced alkaline diuresis, recovery of water and electrolytic balance and an acid-base state.

Overdose symptoms from average to heavy degree:
- a respiratory alkalosis with a compensatory metabolic acidosis;
- hyper pyrexia (extremely high temperature of a body);
- breath disturbances: hyperventilation, not cardiogenic fluid lungs, respiratory depression, asphyxia;
- disturbances from cardiovascular system: disturbances of a heart rhythm, pressure decrease, oppression of cordial activity;
- disturbances of water and electrolytic balance: dehydration (dehydration), the renal failure from an oliguria up to development of a renal failure which is characterized by a hypopotassemia, a hypernatremia, a hyponatremia;
- glucose metabolism disturbance: a hyperglycemia, a hypoglycemia (especially at children), ketoacidosis;
- sonitus, deafness;
- gastrointestinal bleedings;
- hematologic disturbances: from inhibition of aggregation of thrombocytes to a coagulopathy, lengthening of a prothrombin time, a prothrombinopenia;
- neurologic disturbances: toxic encephalopathy and oppression of the TsNS function (drowsiness, confusion of consciousness, lump, spasm).
Treatment: immediate hospitalization in specialized departments for performing the emergency therapy - gastric lavage, multiple dose of absorbent carbon, the forced alkaline diuresis, a hemodialysis, recovery of water and electrolytic balance and an acid-base state, symptomatic therapy.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

The tablets covered with a film kishechnorastvorimy cover, 50 mg and 100 mg.
On 10 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 2, 3 blister strip packagings on 10 tablets or 30 tablets together with the application instruction in a pack from a cardboard.