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

Excipients: corn starch 9.50 mg or 19.00 mg; Potato starch 2.00 mg or 4.00 mg; cellulose microcrystalline 9.07 mg or 18.15 mg; citric acid 3.43 mg or 6.86 mg; magnesium stearate 0.15 mg or 0.30 mg;

shell: hypromellose 0.36 mg or 0.72 mg; Macrogol-4000 0.07 mg or 0.14 mg; talc 0.22 mg or 0.44 mg.

Description:

Round, biconvex tablets, covered with a film membrane of white color, with a risk on one side. Allowed a slight marbling. On the cross section, the nucleus is almost white.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

N.02.B.A.51 Acetylsalicylic acid in combination with other drugs, excluding psycholeptics

Pharmacodynamics:

The mechanism of antiplatelet action acetylsalicylic acid (ASA) is irreversible inhibition of the enzyme cyclooxygenase (COX-1), which blocks the synthesis of thromboxane A2 and aggregation of platelets is suppressed.

Antiaggregatory effect is most pronounced in platelets, since they are not able to re-synthesize COX. It is believed that ASA has other mechanisms for suppressing platelet aggregation, which expands its use in various vascular diseases. ASA also has anti-inflammatory, antipyretic and analgesic effects.

Magnesium hydroxide antacid agent; reduces the irritating effect of ASA on the gastric mucosa.

Pharmacokinetics:

Absorption. After ingestion ASA quickly and almost completely absorbed from the gastrointestinal tract. Eating slows down absorption. Partially metabolized during absorption.

Distribution and Metabolism. During and after absorption, ASA is converted to the main metabolite, salicylic acid, which is metabolized under the influence of enzymes, mainly in the liver, with the formation of metabolites (phenyl salicylate, glucuronide salicylate and salicyluric acid),found in many tissues and body fluids. In women, the metabolic process is slower (less enzyme activity in the blood serum).

The maximum concentration of ASA in the blood plasma is reached 10-20 minutes after ingestion, salicylic acid - after 0.3-2 hours. ASA and salicylic acid are highly associated with blood plasma proteins and are rapidly distributed in the body. The degree of binding of salicylic acid to blood plasma proteins depends on the concentration, not linear. At low concentrations (<100 μg / ml) up to 90% of salicylic acid binds to blood plasma proteins, at high concentrations (> 400 μg / ml) - up to 75%. Bioavailability of ASA is 50-68%, salicylic acid - 80-100%. Salicylic acid penetrates the placental barrier, is found in breast milk.

With renal failure, pregnancy and newborns salicylates can displace bilirubin from bonding with albumin and promote the development of bilirubin encephalopathy.

Excretion. ASA and its metabolites are excreted mainly by the kidneys. The half-life of ASA from the blood plasma is 15-20 minutes, salicylic acid - 2-3 hours with ASA in low doses and increases significantly when taking ASA in high doses as a result of saturation of enzyme systems.Unlike other salicylates, with repeated administration of the drug, unhydrolyzed ASA does not accumulate in the blood serum. In patients with normal renal function, 80-100% of a single dose of ASA is excreted by the kidneys within 24-72 hours.

Magnesium hydroxide in the applied doses does not affect the bioavailability of acetylsalicylic acid.

Indications:

- Primary prevention of cardiovascular diseases, such as thrombosis and acute heart failure, in the presence of risk factors (eg, diabetes, hyperlipidemia, hypertension, obesity, smoking, old age);

- prevention of recurrent myocardial infarction and thrombosis of blood vessels;

- unstable angina;

- prevention of thromboembolism after vascular surgery (eg, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty).

Contraindications:

- Hypersensitivity to ASA, any of the excipients of the drug, other non-steroidal anti-inflammatory drugs (NSAIDs);

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

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

- erosive and ulcerative lesions of the gastrointestinal tract in the phase of exacerbation; gastrointestinal bleeding;

- hemorrhage in the brain;

- propensity to bleeding (thrombocytopenia, hemorrhagic diathesis, vitamin K deficiency);

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

- severe hepatic insufficiency (more than 9 points on the Child-Pugh scale); pregnancy (I and III trimesters);

- the period of breastfeeding;

- deficiency of glucose-6-phosphate dehydrogenase; simultaneous use with methotrexate in a dose of 15 mg or more per week;

- Children under 18 years of age (effectiveness and safety not established).

Carefully:

Gout, hyperuricemia; ulcerative lesions of the gastrointestinal tract or gastrointestinal hemorrhage in the anamnesis, renal insufficiency of mild and moderate severity (creatinine clearance more than 30 ml / min) and / or hepatic insufficiency (9 or less points on the Child-Pugh scale), bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis and paranasal sinuses, allergic reactions; period before surgery interference; simultaneous use with the following drugs: methotrexate in a dose of less than 15 mg per week, valproic acid, anticoagulants, thrombolytic and antiplatelet agents, NSAIDs and ASA derivatives in high doses, narcotic analgesics, sulfonamides (including cotrimoxazole), inhibitors of carbonic anhydrase (acetazolamide), digoxin, lithium, hypoglycemic agents for ingestion (sulfonylurea derivatives), insulin, selective serotonin reuptake inhibitors, ibuprofen, systemic glucocorticosteroids; joint application with ethanol (alcohol-containing preparations, drinks); II trimester of pregnancy.

Pregnancy and lactation:

Pregnancy. The use of salicylates in doses of more than 300 mg / day in the first 3 months of pregnancy is associated with an increased incidence of fetal developmental defects (cleft palate, heart defects). Application preparation of TromboMag® in the first trimester of pregnancy is contraindicated.

In the second trimester of pregnancy, the TromboMag® preparation can be used only after a rigorous assessment of the benefit-treatment relationship for the mother and the potential risk to the fetus, at doses not exceeding 150 mg / day and for a short time.

In the third trimester of pregnancy, salicylates (at a dose of 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 application immediately before childbirth can cause intracranial hemorrhage, especially in premature infants. Application of the drug TromboMag® in the III trimester of pregnancy is contraindicated.

Breastfeeding period. Salicylates and their metabolites penetrate into breast milk in small amounts. Clinical data for assessing the safety of ASA in the period of breastfeeding is not enough. Before prescribing ASA during lactation, the potential benefit of therapy with a drug regarding the potential risk to infants should be assessed. 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, if prolonged use of the TromboMag® preparation is necessary, breastfeeding should be stopped immediately (see "Contraindications").

Dosing and Administration:

Inside, 1-2 hours after meals, once a day.

The tablet of the preparation TromboMag® is swallowed whole (can be chewed or grinded), washed down with water.

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

Primary prevention of cardiovascular diseases, such as thrombosis and acute heart failure, in the presence of risk factors (for example, diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking, old age)

On the first day - 1 tablet of the preparation TromboMag®, containing 150 mg

acetylsalicylic acid, followed by 1 tablet of the preparation ThromboMag®, containing 75 mg of acetylsalicylic acid.

Prevention of repeated myocardial infarction and thrombosis of blood vessels

1 tablet of the preparation TromboMag®, containing 75 mg or 150 mg of acetylsalicylic acid.

Unstable angina

1 tablet of the preparation TromboMag®, containing 75 mg or 150 mg of acetylsalicylic acid.

Preventing thromboembolism after vascular surgery (eg, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty)

1 tablet of the preparation TromboMag®, containing 75 mg or 150 mg of acetylsalicylic acid.

If you miss one or more doses of the drug ThromboMag® should be taken at the same dose as soon as the patient remembers it. To avoid doubling the dose, do not take the missed tablet if the time of taking the next dose is approaching.

Features of the action when the drug is first taken or withdrawn were not observed.

Side effects:

In general, the preparation of TromboMag®, containing low-dose ASA and antacid agent of magnesium hydroxide, is well tolerated.

The frequency of the side effects listed below is determined in accordance with the classification of the World Health Organization: Often - more than 10%; often - more than 1% and less than 10%; infrequently - more than 0,1% and less than 1%; rarely - more than 0,01% and less than 0,1%; rarely - less than 0.01%, including individual messages.

From the central nervous system:

often - headache, insomnia;

infrequently - dizziness, drowsiness; rarely - noise in the ears, intracerebral hemorrhage.

On the part of the hematopoiesis system:

Often increased bleeding;

rarely - anemia; rarely - Aplastic anemia, hypoprothrombinemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, agranulocytosis.

There are reports of hemolysis and hemolytic anemia in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.

From the respiratory system:

often - bronchospasm.

From the digestive system:

Often - Heartburn;

often - nausea, vomiting;

infrequently - pain in the abdomen, ulcers of the mucous membrane of the stomach and duodenum, including perforating (rare), gastrointestinal bleeding;

rarely - increased activity of "liver" enzymes; rarely - stomatitis, esophagitis, erosive lesions of the upper sections of the gastrointestinal tract (including strictures), colitis, irritable bowel syndrome.

Allergic reactions:

infrequently - Urticaria, Quincke edema, skin rash, skin itch, rhinitis, edema of the nasal mucosa;

rarely - Anaphylactic shock, cardiorespiratory distress syndrome.

Other:

rarely - impaired renal function.

Overdose:

Early signs of an overdose of salicylates (salicilism) include tinnitus / ringing in the ears and develop at a plasma concentration of about 200 μg / mL. Severe toxic effects are associated with salicylate concentrations> 400 μg / ml.

Symptoms of an overdose of moderate severity: nausea, vomiting, tinnitus, hearing impairment, dizziness, confusion.

Treatment: gastric lavage, repeated intake of activated charcoal;

symptomatic therapy.

Symptoms of a severe overdose: fever, hyperventilation, ketoacidosis, respiratory alkalosis, severe hypoglycemia, cardiovascular and respiratory failure, coma.

Treatment: immediate admission to a specialized department for emergency treatment (gastric lavage, repeated intake of activated charcoal, alkaline and forced alkaline diuresis, hemodialysis, restoration of water electrolyte and acid-base state, symptomatic therapy). When conducting alkaline diuresis, it is necessary to achieve a pH value of urine within the range of 7.5-8.0. Forced alkaline diuresis should be performed when the concentration of salicylates in the blood plasma is more than 500 mg / L (3.6 mmol / L) in adults and 300 mg / L (2.2 mmol / L) in children. Overdose is especially dangerous in elderly patients.

Interaction:

- When combined ASA enhances action and increases the risk of toxicity methotrexate (due to a decrease in renal clearance and displacement from the connection with plasma proteins) and valproic acid (due to the displacement of plasma from the connection with proteins).

- ASA intensifies the action and increases the risk of unwanted reactions:

narcotic analgesics, other non-steroidal anti-inflammatory drugs (due to the synergy of the action);
hypoglycemic agents for ingestion (sulfonylurea derivatives) and insulin (due to hypoglycemic properties of ASA itself in high doses (more than 2 g per day) and displacement of sulfonylurea derivatives from binding to plasma proteins);
thrombolytic drugs, heparin, indirect anticoagulants (including ticlopidine, warfarin), antiplatelet agents (including clopidogrel, dipyridamole) - due to synergism of the main therapeutic effects and the displacement of blood plasma from proteins;
sulfonamides, including co-trimoxazole - due to the displacement of plasma from the connection with proteins and the increase in the concentration in the blood plasma;
inhibitors of carbonic anhydrase (acetazolamide).Joint application with ASA may lead to the development of severe acidosis and enhance the toxic effect on the central nervous system;
digoxin and lithium - by decreasing the renal excretion of digoxin and lithium with increasing their concentration in the blood plasma;
selective serotonin reuptake inhibitors (Including sertraline, paroxetine) - due to the synergy of action (to increase the risk of bleeding from the upper gastrointestinal tract);
ethanol (Alcohol and alcohol-containing medications) - with the strengthening of the damaging effect on the mucous membrane of the gastrointestinal tract and an increased risk of gastrointestinal bleeding.

- Reduce the antiplatelet effect of ASA:

ibuprofen (due to antagonism with respect to inhibition of platelet aggregation);
systemic glucocorticosteroids (enhance the elimination of salicylates);
antacids containing magnesium and / or aluminum hydroxide, colestyramine (reduce the absorption of ASA in the gastrointestinal tract).

- ASC in low doses weakens the effect uricosuric drugs (Benzbromaron, probenecid, sulfinpyrazone) - due to the competitive suppression of renal tubular excretion of uricacid.

- ASC in high doses, like other NSAIDs, can reduce the antihypertensive effect diuretics (due to a decrease in the glomerular filtration rate due to suppression of the synthesis of renal prostaglandins) and antihypertensive drugs. In particular, due to a competitive blockade of prostacyclin synthesis, a decrease in efficacy inhibitors angiotensin-converting enzyme (ACE).

Special instructions:

- The drug TromboMag® should be used as directed by a doctor.

- ASA can provoke bronchospasm, cause seizures of bronchial asthma and other reactions of hypersensitivity (see the sections "Contraindications", "With caution"). The presence in history of bronchial asthma, hay fever, nasal polyposis and paranasal sinuses, chronic respiratory diseases, as well as allergic reactions to other drugs (for example, skin reactions, itching, urticaria) are risk factors.

- The inhibitory effect of ASA on platelet aggregation persists for several days after admission, which should be taken into account during and after surgical intervention. A few days before the planned surgery, the risk of bleeding should be assessed in comparison with the risk of developing ischemic complications.If there is a significant risk of bleeding, taking TromboMag® should be temporarily discontinued (see "With caution").

- In case of impaired renal function (creatinine clearance more than 30 ml / min), as well as for circulatory disorders resulting from arteriosclerosis of the renal arteries, chronic heart failure, extensive surgical intervention, sepsis, cases of massive bleeding, caution should be used, since in all listed cases, ASA may increase the risk of developing acute renal failure / impaired renal function (see "With caution").

It is known that the risk of developing acute renal failure increases with the joint use of other NSAIDs with ACE inhibitors or diuretics. Monitoring of renal function is recommended.

- In patients with mild to moderate liver failure, liver function should be monitored regularly (see "With caution").

- Joint application ASA and methotrexate is accompanied by an increased incidence of side effects from the hematopoiesis, a joint application with valproic acid - an increased risk of its toxicity.During the first weeks of the joint use of the drug TromboMag® and methotrexate in a dose of less than 15 mg per week, a blood test should be performed weekly. Careful monitoring should be performed in the presence of even small violations of kidney function, as well as in elderly patients (see the sections "Contraindications", "With caution", "Interaction with other drugs").

Joint use of ASA with anticoagulants, thrombolytic and antiplatelet agents is associated with an increased risk of bleeding and damage to the mucous membrane of the gastrointestinal tract (see sections "With caution", "Interaction with other drugs"). It is necessary to control the time of bleeding.

It is not recommended joint use of the preparation TromboMag® and ibuprofen in patients with an increased risk of cardiovascular diseases, since a decrease in the antiplatelet effect of ASA in doses up to 300 mg leads to a decrease in cardioprotective effects. Patients receiving ibuprofen to relieve pain, you should inform your doctor about this (seesections "With care", "Interaction with other medicinal products").

It is recommended to monitor the concentrations of digoxin and lithium in blood plasma at the beginning or at the end of the joint use of the preparation TromboMag®; a dose adjustment may be required (see "With caution", "Interaction with other drugs").

With the joint use of systemic glucocorticosteroids (GCS) and ASA, the concentration of salicylates in the blood plasma is reduced, and after the abolition of systemic SCS, an overdose of salicylates is possible. In addition, when combined use increases the risk of damage to the mucous membrane of the gastrointestinal tract and bleeding (see sections "With caution", "Interaction with other drugs").

In the joint use of ASA with diuretics and antihypertensive agents (eg, ACE inhibitors), possible reduction in their effectiveness should be considered (see section "Interaction with other drugs").

- Reception ASC in doses exceeding the recommended therapeutic (patients of any age), or long reception ASA in low doses (elderly patients) are associated with an increased risk of gastrointestinal bleeding. With prolonged use of the TromboMag® drug, you should periodically monitor the general blood test and stool test for latent blood, as well as the functional state of the liver.

ASA in low doses reduces the excretion of uric acid and can provoke the development of gout in predisposed patients who have decreased excretion of uric acid (see section "With caution", "Interaction with other drugs").

ASA in high doses has a hypoglycemic effect, which should be taken into account in patients with diabetes mellitus, who receive hypoglycemic agents for ingestion or insulin (see section "With caution", "Interaction with other drugs").

In severe forms of deficiency of glucose-6-phosphate dehydrogenase ASA can cause hemolysis and hemolytic anemia (see section "Contraindications"). Factors that increase the risk of hemolysis and hemolytic anemia are fever, acute infections and high doses of ASA.

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

During the period of treatment with TromboMag®, care must be taken when driving vehicles and carrying out activities requiring an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 75 mg + 15.2 mg and 150 mg + 30.39 mg.

Packaging:

10 tablets in a contour mesh box made of foil of aluminum printed lacquered and aluminum foil, laminated with polyvinylchloride and polyamide film.

3 or 10 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In a place protected from moisture and light, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years.

Do not use after the expiration date stated on the package

Terms of leave from pharmacies:On prescription

Registration number:LP-003550

Date of registration:01.04.2016

Date of cancellation:2021-04-01

The owner of the registration certificate:NIZHFARM, JSC NIZHFARM, JSC Russia

Manufacturer: & nbsp

HEMOFARM, LLC Russia

Representation: & nbspNizhpharm, JSCNizhpharm, JSCRussia

Information update date: & nbsp13.06.2016

Illustrated instructions

Instructions

TromboMag® (TromboMag®)