Trombo ACC - instructions for use, doses, side effects, contraindications

Acetylsalicylic acid (ASA) is an ester of salicylic acid, belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs).The mechanism of action is based on the irreversible inactivation of the enzyme cyclooxygenase (COX-1), which blocks the synthesis of prostaglandins, prostacyclin and thromboxane. Reduces aggregation, adhesion thrombocytes and thrombus formation by suppressing the synthesis of thromboxane A2 in platelets.

Increases fibrinolytic activity of blood plasma and reduces the concentration of vitamin K-dependent coagulation factors (II, VII, IX, X). The antiaggregant effect is most pronounced in platelets, since they are unable to re-synthesize cyclooxygenase. Antiaggregant effect develops after the application of small doses of the drug and persists for 7 days after a single dose. These properties of ASA are used in the prevention and treatment of myocardial infarction, ischemic heart disease, complications of varicose veins.

ASA also has anti-inflammatory, antipyretic and analgesic effects.

Pharmacokinetics:

When administered orally, ASA is absorbed rapidly and completely from the gastrointestinal tract. The Trombo ACC tablets are coated with an enteric coating, which reduces the direct irritant effect of ASA on the gastric mucosa.ASA is partially metabolized during absorption. During and after absorption, ASA is converted to a major metabolite, salicylic acid, which is metabolized mainly in the liver under the influence of liver enzymes to form metabolites such as phenyl salicylate, glucuronide salicylate and salicyluric acid, found in many tissues and in urine. In women, the metabolic process is slower (less enzyme activity in the blood serum).

ASA and salicylic acid are highly associated with blood plasma proteins (from 66 to 98%, depending on the dose) and are quickly distributed in the body. Salicylic acid penetrates the placenta and is excreted in breast milk.

The half-life of ASA from the blood plasma is about 15-20 minutes. Unlike other salicylates, with repeated administration of the drug, unhydrolyzed ASA does not accumulate in the blood serum. Only 1% of an oral ASA excreted by the kidneys in the form negidrolizirovannoy ACK, the remainder is output as salicylates and their metabolites. In patients with normal kidney function, 80-100% of a single dose of the drug is excreted by the kidneys within 24-72 hours.

Indications:

- Primary prevention of acute myocardial infarction in the presence of risk factors (eg, diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking, old age);

- secondary prevention of myocardial infarction (repeated);

- stable and unstable angina;

- prevention of stroke (including, in patients with transient impairment of cerebral circulation);

- prophylaxis of transient cerebral circulation;

- prevention of thromboembolism after surgery and invasive vascular interventions (eg, coronary artery bypass grafting, carotid endarterectomy, angioplasty, and stenting of the coronary arteries);

- prevention of deep vein thrombosis and thromboembolism of the pulmonary artery and its branches (including, with prolonged immobilization as a result of extensive surgical intervention).

Contraindications:

- Hypersensitivity to ASA, excipients in the composition drug and other NSAIDs;

- erosive and ulcerative lesions, gastrointestinal tract (in the phase of exacerbation);

- gastrointestinal bleeding;

- hemorrhagic diathesis;

- The bronchial asthma, induced by the intake of salicylates and other NSAIDs;

- combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and ASA intolerance;

- combined use with methotrexate at a dose of 15 mg per week or more;

- pregnancy (I and III trimester) and lactation;

- age to 18 years;

- marked renal failure (creatinine clearance (CK) less than 30 ml / min);

- marked hepatic insufficiency (class B and higher on the Child-Pugh scale);

- chronic heart failure III-IV functional class for classification of NYHA;

- lactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Carefully:

With gout, hyperuricemia, peptic ulcer and duodenal ulcer or gastrointestinal hemorrhage (in the anamnesis), renal failure (QC more than 30 ml / min), liver failure (lower class B on the Child-Pugh scale), bronchial asthma, chronic diseases of the respiratory system, hay fever, nasal polyposis, drug allergy, including, drugs of the NSAID group, analgesics, anti-inflammatory, antirheumatic drugs; pregnancy (II term), with the proposed surgical intervention (including minor, for example,tooth extraction); with simultaneous admission with the following medicines (see section Interactions with other medicinal products):

- methotrexate in a dose of less than 15 mg per week;

- with anticoagulants, thrombolytic or antiplatelet agents;

- with NSAIDs and salicylic acid derivatives in large doses;

- with digoxin;

- with hypoglycemic agents for oral administration (derivatives of sulfonylureas) and insulin;

- with valproic acid;

- with alcohol (alcoholic beverages in particular);

- with selective serotonin reuptake inhibitors;

- with ibuprofen.

Pregnancy and lactation:

Application in pregnancy

The use of large doses of salicylates in the first 3 months of pregnancy is associated with an increased incidence of fetal developmental defects (split upper skies, heart defects). The use of salicylates in the first trimester of pregnancy is contraindicated.

In the last trimester of pregnancy, salicylates in high doses (more than 300 mg / day) cause inhibition of labor, premature closure of the arterial duct in the fetus, increased bleeding in the mother and fetus, and the appointment immediately before childbirth can cause intracranial hemorrhages, especially in premature infants.The use of salicylates in the last trimester of pregnancy is contraindicated.

In the second trimester of pregnancy, salicylates can only be used with strict risk and benefit estimates for the mother and fetus, preferably at doses not higher than 150 mg / day and for a short time.

Application during lactation

Salicylates and their metabolites penetrate into breast milk in small amounts. The accidental intake of salicylates during lactation is not accompanied by the development of adverse reactions in the child and does not require the cessation of breastfeeding. However, with prolonged use of the drug or its use in a high dose, breast-feeding should be stopped immediately.

Dosing and Administration:

Tablets of the drug Trombo ACC® should be taken before meals, washed down with a large amount of liquid. The drug is not taken on an empty stomach

The drug is intended for long-term use. The duration of therapy is determined by the doctor.

- Primary prevention of acute myocardial infarction in the presence of factors risk: 50-100 mg per day.

- Prevention of repeated myocardial infarction, angina: 50-100 mg at day.

- Prevention of stroke and transient disorders of cerebral circulation: 50-100 mg per day.

- Preventive maintenance of a thromboembolism after operation and invasive interventions on vessels: 50-100 mg a day.

- Prevention of deep vein thrombosis and thromboembolism of the pulmonary artery and its branches: 100-200 mg (2 tablets) in day.

Side effects:

In general, Trombo ACC® due to low dosage is well tolerated by patients, however in rare cases the following undesirable effects may occur:

From the digestive tract: nausea, heartburn, vomiting, pain in the abdomen; rarely - stomach and duodenal ulcers, including perforating, gastrointestinal bleeding, transient liver dysfunction with increased activity of "liver" transaminases.

From the central nervous system: dizziness, hearing loss, tinnitus, which may be a sign of drug overdose (see Overdose section).

On the part of the hematopoiesis system: increased frequency of perioperative (intra- and post-operative) bleeding, hematomas, nasal bleeding, bleeding gums, bleeding from the urogenital tract. There are reports of serious cases of bleeding, which include gastrointestinal bleeding and hemorrhage in the brain (especially in patients with hypertension,who did not reach the target of blood pressure (BP) and / or who received concomitant therapy with anticoagulant drugs), which in some cases may be life-threatening. Bleeding can lead to the development of acute or chronic posthemorrhagic / iron deficiency anemia (eg, due to latent bleeding) with appropriate clinical and laboratory symptoms (asthenia, pallor, hypoperfusion).

Allergic reactions: skin rash, itching, urticaria, Quincke's edema, rhinitis, mucous membrane swelling of the nasal cavity, rhinitis, bronchospasm, cardio-respiratory distress syndrome, as well as severe reactions, including anaphylactic shock.

Overdose:

It can have serious consequences, especially in elderly patients and children. The syndrome of salicylism develops when taking ASA at a dose of more than 100 mg / kg / day for more than 2 days due to the use of toxic doses of the drug in the context of improper therapeutic use (chronic poisoning) or a single accidental or intentional intake of a toxic dose of the drug by an adult or child (acute poisoning).

Symptoms of overdose:

- with mild and moderate severity (single dose less than 150 mg / kg): dizziness, tinnitus, hearing loss, increased sweating, nausea and vomiting, headache, confusion; tachypnea, hyperventilation, respiratory alkalosis.

Treatment: gastric lavage, repeated intake of activated carbon, forced alkaline diuresis, restoration of water-electrolyte balance and acid-base state.

- with moderate to severe severity (single dose 150 mg / kg-300 mg / kg - moderate severity, more than 300 mg / kg - severe poisoning): respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, hyperventilation, non-cardiogenic pulmonary edema, respiratory depression, asphyxia; from the cardiovascular system: heart rhythm disturbances, marked decrease in blood pressure, suppression of cardiac activity; from the side of water-electrolyte balance: dehydration, disturbance of kidney function from oliguria up to the development of renal failure, characterized by hypokalemia, hypernatremia, hyponatremia; impaired glucose metabolism: hyperglycemia, hypoglycemia (especially in children),ketoacidosis; noise in the ears, deafness; gastrointestinal bleeding; hematological disorders: from inhibition of platelet aggregation to coagulopathy, prolongation of prothrombin time, hypoprothrombinemia; neurological disorders: toxic encephalopathy and depression of the central nervous system (drowsiness, confusion, coma, convulsions).

Treatment: immediate hospitalization in specialized departments for emergency therapy - gastric lavage, repeated intake of activated carbon, forced alkaline diuresis, hemodialysis, restoration of water-electrolyte balance and acid-base state, symptomatic therapy.

Interaction:

With the simultaneous use of ASA strengthens action of the following medicines; if it is necessary to simultaneously apply ASA with the listed means, consider the need to reduce the dose of these funds:

- methotrexate, by reducing renal clearance and displacing it from the bond with proteins;

- with simultaneous use with anticoagulants, thrombolytic and antiplatelet agents (ticlopidine, clopidogrel) is noted increased risk of bleeding due to synergy of the main therapeutic effects of the drugs used;

- with simultaneous application with drugs that have anticoagulant, thrombolytic or antiplatelet effect, increased damage to the mucosa of the gastrointestinal tract;

- selective serotonin reuptake inhibitors, which may lead to an increased risk of bleeding from the upper GI tract (synergy with ASA);

- digoxin, due to a decrease in its renal excretion, which can lead to an overdose;

- hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin due to hypoglycemic properties of the ASA itself at high doses and displacement of the sulfonylurea derivatives from binding to blood plasma proteins;

- when used with valproic acid, its toxicity increases due to the displacement of its binding to blood plasma proteins;

- NSAIDs and salicylic acid derivatives in high doses (increased risk of ulcerogenic effect and bleeding from the gastrointestinal tract as a result of synergism of action); while simultaneous application with ibuprofen, antagonism is noted with respect toirreversible inhibition of platelets due to the action of ASA, which leads to a decrease cardioprotective effects of ASA;

- ethanol (increased risk of damage to the mucous membrane of the gastrointestinal tract and prolonged bleeding time due to the mutual enhancement of the effects of ASA and ethanol).

Simultaneous use of ASA in high doses can loosen action of the medicines listed below; if it is necessary to simultaneously prescribe ASA with the listed means, consideration should be given to the need to correct the dose of the listed drugs:

- any diuretics (when combined with ASA in high doses, there is a decrease in the glomerular filtration rate (GFR) as a result of a decrease in the synthesis of prostaglandins in the kidneys);

- inhibitors of angiotensin-converting enzyme (ACE) (a dose-dependent decrease in GFR due to inhibition of prostaglandins with vasodilating action, respectively, weakening of hypotensive action, clinical decrease in GFR is observed with a daily dose of ASC greater than 160 mg. In addition, there is a decrease in the positive cardioprotective effect of ACE inhibitors,assigned to patients for the therapy of chronic heart failure. This effect also manifests when applied in conjunction with ASA in large doses).

- drugs with uricosuric action - benzbromarone, probenecid (reduction of uricosuric effect due to competitive suppression of renal tubular excretion of uric acid);

- when used simultaneously with systemic glucocorticosteroids (with the exception of hydrocortisone used for the replacement therapy of Addison's disease), the salicylate excretion is increased and, accordingly, their effect is weakened.

Special instructions:

The drug should be used after the appointment of a doctor.

ASA can provoke bronchospasm, as well as cause seizures of bronchial asthma and other reactions of hypersensitivity. Risk factors are the availability of a history of asthma, hay fever, nasal polyposis, chronic diseases of the respiratory system as well as of allergic reactions to other drugs (e.g., skin reactions, pruritus, urticaria).

The inhibitory effect of ASA on platelet aggregation persists for several days after administration, in connection with which,possibly an increased risk of bleeding during surgery or in the postoperative period. If absolute elimination of bleeding is necessary in the course of surgical intervention, it is necessary, if possible, to completely abandon the use of ASA in the preoperative period.

The combination of ASA with anticoagulants, thrombolytic agents and antiaggregant drugs is accompanied by an increased risk of bleeding.

ASA in low doses can provoke the development of gout in predisposed individuals (having a decreased excretion of uric acid). The combination of ASA with methotrexate is accompanied by an increased incidence of side effects from the hematopoiesis.

High doses of ASA have a hypoglycemic effect, which must be borne in mind when prescribing it to patients with diabetes mellitus receiving hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin.

When combined glucocorticosteroids (glucocorticosteroids) and salicylates should be remembered that during treatment, the level of salicylates in the blood is lowered, and after overtreatment of SCS, an overdose of salicylates is possible.

The combination of ASA with ibuprofen in patients with an increased risk of cardiovascular disease is not recommended, since the latter reduces the positive effect of ASA on life expectancy (reduces the cardioprotective effect of ASA).

Excess dose of ASA is associated with a risk of gastrointestinal bleeding. Overdose is especially dangerous in elderly patients.

When a combination of ASA with ethanol (alcoholic beverages) is increased the risk of damage to the mucosa of the gastrointestinal tract and prolong the time of bleeding.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, as the use of the Trombo ACC® product may cause dizziness.

Form release / dosage:Tablets coated with enteric film coating 50 mg and 100 mg.

Packaging:For 14 tablets or 20 tablets per PVC / Al blister. 2 blisters (for 14 tablets) or 5 blisters (for 20 tablets) together with instructions for use in a cardboard pack.

Storage conditions:

Keep in dry the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

Shelf life 3 years.

Do not use after expiry date.

Terms of leave from pharmacies:Without recipe

Registration number:П N013722 / 01

Date of registration:01.11.2011

The owner of the registration certificate:VALEANT, LLC VALEANT, LLC Russia

Manufacturer: & nbsp

LANNACHER HEILMITTEL, GmbH Austria

Representation: & nbspVALEANT LLC VALEANT LLC Russia

Information update date: & nbsp16.05.2014

Illustrated instructions

Instructions

Trombo ACC® (Thrombo ASS®)