Тромбопол®

General characteristics. Structure:

Active ingredient: 75 mg or 150 mg of acetylsalicylic acid.

Excipients: starch corn, cellulose microcrystallic, sodium carboxymethylstarch.

Cover: a gipromelloza, Akril-Ayz (mix for a covering of tablets): methacrylic acid copolymer type C, talc, titanium dioxide, triethyl citrate, dye crimson [Ponso 4R], silicon dioxide colloid, Natrii hydrocarbonas, sodium lauryl sulfate.

Pharmacological properties:

Pharmacodynamics. Irreversible inhibition of cyclooxygenase (TsOG – 1) is the cornerstone of the mechanism of antiagregantny effect of acetylsalicylic acid therefore synthesis of A 2 thromboxane is blocked 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. These properties of acetylsalicylic acid are used in prevention and treatment of a myocardial infarction, coronary heart disease, varicosis complications.

Acetylsalicylic acid (ASK) also has antiinflammatory, febrifugal and analgeziruyushchy effect.

^{The tablets TROMBOPOL®} have a kishechnorastvorimy cover thanks to which are dissolved and emit active agent in more alkaline environment of a duodenum, reducing irritant action of acetylsalicylic acid by a mucous membrane of a stomach.

Pharmacokinetics. Absorption of acetylsalicylic acid from the tablets covered with a kishechnorastvorimy cover begins in 3-4 hours from the moment of administration of drug, confirming that the cover effectively blocks dissolution of drug in a stomach.

The maximum concentration in plasma is observed approximately in 2-3 hours and averages 12,7 mkg/ml for tablets of 150 mg and 6,72 mkg/ml for tablets of 75 mg.

Existence of food in digestive tract slows down drug absorption. Speed of system absorption (AUC) makes 56,42 mkg x hour/ml for tablets of 75 mg and 108,08 mkg x hour/ml for tablets of 150 mg.

Distribution. Acetylsalicylic acid quickly and substantially gets into the majority of fabrics and biological liquids of an organism.

Relative distribution makes about 0,15-0,2 l/kg and increases along with increase in concentration of drug in blood serum. Extent of communication of drug with proteins of a blood plasma depends on concentration; at healthy faces decreases along with reduction of this concentration.

At a renal failure, at pregnancy and at newborns salicylates can force out bilirubin from communication with albumine and promote development of bilirubinovy encephalopathy.

Metabolism. Acetylsalicylic acid is partially metabolized during absorption. This process happens under the influence of enzymes, mainly, in a liver to formation of such metabolites as salol, a glucuronide salicylate and salitsilurovy acid, found in many fabrics and urine.

At women process of metabolism takes place more slowly (smaller activity of enzymes in blood serum).

Removal. The elimination half-life (T ½) acetylsalicylic acid makes about 15-20 minutes of a blood plasma. Unlike other salicylates, at multiple dose of drug not hydrolyzed acetylsalicylic acid does not collect in blood serum.

Only 1% of the dose of acetylsalicylic acid accepted inside is removed by kidneys in the form of not hydrolyzed acetylsalicylic acid, other part is removed in the form of salicylates and their metabolites.

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:

• 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;
• prevention of a stroke (including, at patients with passing disturbance of cerebral circulation);
• prevention of 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 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:

Pill should be taken irrespective of meal, without chewing, washing down with a small amount of water. Drug is intended for prolonged use. Duration of therapy is defined by the doctor.

Prevention at suspicion of an acute myocardial infarction: 75 mg or 150 mg a day.

Prevention for the first time the arisen acute myocardial infarction with risk factors: 75 mg or 150 mg a day.

Prevention of a repeated myocardial infarction. Unstable stenocardia. Prevention of a stroke and passing disturbance of cerebral circulation. Prevention of tromboembolic episodes after surgeries or invasive researches: 75 mg or 150 mg a day.

Prevention of a deep vein thrombosis and thromboembolism of a pulmonary artery and its branches: 75 mg or 150 mg a day.

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).

ASK can cause bleedings of various degree of manifestation in time and after surgical interventions. Administration of drug needs to be stopped in 5-7 days prior to alleged operation.

ASK combination to anticoagulants, thrombolytic drugs and inhibitors of aggregation of thrombocytes is followed by the increased risk of development of bleedings.

ASK in low doses can provoke development of gout in the predisposed persons (having reduced excretion of uric acid).

ASK combination to a methotrexate is followed by the increased frequency of development of side effects from bodies of a hemopoiesis.

High doses of ASK render hypoglycemic effect that patients need to mean at appointment it with the diabetes mellitus receiving hypoglycemic means.

At the combined purpose of glucocorticosteroids (GKS) and salicylates it is necessary to remember that during treatment the level of salicylates in blood is reduced, and after cancellation of GKS the overdose of salicylates is possible.

ASK combination to an ibuprofen as it reduces efficiency of the drug TROMBOPOL® and thereof, can reduce life expectancy is not recommended. Exceeding of a dose of ASK is accompanied by risk of gastrointestinal bleeding.

At ASK combination to ethanol the risk of injury of a mucous membrane of digestive tract and lengthening of a bleeding time is increased.

The overdose is especially dangerous at elderly people. Patients are more senior than 65 years because of the lowered operability of kidneys and more frequent emergence of side reactions from digestive tract have to accept ASK in smaller doses.

Influence on abilities to concentration of attention and speed of psychomotor reactions. There are no data on negative impact on abilities to driving or work with mechanisms.

Use at pregnancy. Use of salicylates in the I trimester of pregnancy leads to development of splitting of the upper sky, heart diseases; in the III trimester causes braking 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 at premature children — use of salicylates in these trimesters is contraindicated. In the II trimester of pregnancy it is possible to appoint salicylates only taking into account strict assessment of risk and advantage.

Use during feeding by a breast. 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.

Side effects:

Digestive tract: nausea, heartburn, vomiting, pain in a stomach, diarrhea, ulcers of a mucous membrane of a stomach and a duodenum, including perforative, gastrointestinal bleedings, increase in activity of "hepatic" enzymes.

Respiratory system: bronchospasm.

Central nervous system: dizziness, sonitus.

System of a hemopoiesis: the raised bleeding, anemia (seldom).

Allergic reactions: small tortoiseshell, Quincke's edema.

Interaction with other medicines:

At simultaneous use of ASK strengthens effect of the following medicines:

• methotrexate, due to decrease in renal clearance and its replacement from communication with proteins;
• heparin and indirect anticoagulants, due to dysfunction of thrombocytes and replacement of indirect anticoagulants from communication with proteins;
• thrombolytic drugs and inhibitors of aggregation of thrombocytes (tiklopidin);
• digoxin, owing to decrease in its renal excretion;
• hypoglycemic means (insulin and derivatives of sulphonylurea), due to hypoglycemic properties of the ASK in high doses and replacement of derivatives of sulphonylurea from communication with proteins;
• valproic acid, due to replacement of its communication with proteins;
• NPVP;
• streptocides (including, co-trimoxazole);
• barbiturates;
• compounds of lithium.

The additive effect is observed at a concomitant use of ASK with alcohol.

ASK weakens action:

• the antigouty drugs increasing release of uric acid (пробенецид, Sulfinpyrazonum, бензбромарон), owing to competitive tubular elimination of uric acid;
• anti-hypertensive means, including angiotensin-converting enzyme inhibitors;
• antagonists of Aldosteronum (for example, Spironolactonum);
• "loopback" diuretics (for example, furosemide);

Strengthening elimination of salicylates, system glucocorticosteroids weaken their action.

Contraindications:

• Hypersensitivity to acetylsalicylic acid, excipients of drug and other NPVP;
• digestive tract erosive cankers (in an aggravation phase);
• gastrointestinal bleeding;
• hemorrhagic diathesis;
• the bronchial asthma induced by reception of salicylates and NPVP; a combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of ASK;
• the combined use with a methotrexate in a dose of 15 mg a week and more;
• pregnancy (I and III trimester) and lactation period;
• age up to 18 years.

With care: at gout, a hyperuricemia, a peptic ulcer of a stomach and a 12-perstny gut or gastrointestinal bleedings (in the anamnesis), a renal/liver failure, bronchial asthma, chronic diseases of a respiratory organs, hay fever, a polypose of a nose, a medicinal allergy, a concomitant use of a methotrexate in the dose less than 15 mg/week accompanying therapy by anticoagulants, pregnancies (the II trimester).

Overdose:

The first symptoms of overdose of acetylsalicylic acid are: nausea, vomiting, sonitus and hurried breathing. Also such symptoms as can be observed: hearing loss, visual disturbance, headaches, motive excitement, drowsiness, spasms, hyperthermia. At heavy intoxication disturbance of acid-base and water and electrolytic balance (a metabolic acidosis and dehydration) can develop.

Symptoms of slight and medium-weight intoxication develop after use of acetylsalicylic acid in a dose of 150-300 mg/kg. Symptoms of heavy overdose develop at a dose of 300-500 mg/kg. Potentially lethal dose of ASK makes more than 500 mg/kg.

Treatment: the specific antidote is absent. In case of overdose of acetylsalicylic acid it is necessary:

• to cause vomiting and to wash out a stomach (for the purpose of drug absorption reduction). Such actions give effect within 3-4 hours after administration of drug, and in case of reception of very high dose — till 10 o'clock;
• for reduction of absorption of ASK it is necessary to accept absorbent carbon in the form of water suspension (a dose for adults — 50-100 g, for children — 30-60 g);
• it is necessary to watch attentively disturbance of water and electrolytic balance and to fill it;
• for the purpose of acceleration of removal of ASK through kidneys and at treatment of acidosis it is necessary to enter intravenously sodium bicarbonate. It is necessary to support рН within 7,0 — 7,5;
• at very heavy intoxication it is necessary to carry out a hemodialysis or peritoneal dialysis;
• in connection with a possibility of development of a respiratory acidosis it is forbidden to accept the drugs oppressing the central nervous system, for example, barbiturates;
• patients with disturbance of breath need to provide passability of respiratory tracts and access of oxygen. In case of need to execute an intratracheal intubation and to provide artificial ventilation of the lungs.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to use after the expiry date specified on packaging. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

The tablets covered with a kishechnorastvorimy cover, 75 mg or 150 mg.

Tablets of 75 mg: on 10 or 25 tablets in blisters from PVH/AL foil. On 2 blisters (25 tablets) or 3, 5, 6 blisters (10 tablets) with the instruction on a medical use in a cardboard pack.

Tablets of 150 mg: on 10 tablets in the blister from PVH/AL foil. On 3, 5 or 6 blisters with the instruction on a medical use in a cardboard pack