Description
Pharmacological action of
The mechanism of the antiplatelet action of acetylsalicylic acid (ASA) is based on the irreversible inhibition of the cyclooxygenase enzyme (COX-1), as a result of which thromboxane A2 synthesis is blocked and platelet aggregation is suppressed. The anti-aggregation 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 scope in various vascular diseases. ASA also has anti-inflammatory, antipyretic and analgesic effects.
Magnesium hydroxide – an antacid that reduces the irritating effect of ASA on the gastric mucosa.
Absorption. After ingestion, ASA is rapidly and almost completely absorbed from the gastrointestinal tract. Eating slows down absorption. Partially metabolized during absorption.
Distribution and metabolism. During and after absorption, ASA turns into the main metabolite – salicylic acid, which is metabolized under the influence ofEnzymes are mainly found 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 (lesser activity of enzymes in the blood serum).
The maximum concentration of ASA in blood plasma is reached 10-20 minutes after ingestion, salicylic acid – after 0.3-2 hours. ASA and salicylic acid are highly bound to plasma proteins and are rapidly distributed in the body. The degree of binding of salicylic acid to plasma proteins depends on the concentration, not linear. At low concentrations (<100 Ñg / ml), up to 90% of salicylic acid binds to plasma proteins, at high concentrations (> 400 Ñg / ml) up to 75%. The bioavailability of ASA is 50 ² 68%, salicylic acid – 80-100%. Salicylic acid crosses the placental barrier, is found in breast milk.
In renal failure, during pregnancy, and in newborns, salicylates can displace bilirubin from association with albumin and contribute to the development of bilirubin encephalopathy.
Withdrawal. ASA and its metabolites are excreted mainly by the kidneys. The half-life of ASA from blood plasma is 15-20 minutes, salicylic acid – 2-3 hours when taking ASA in low doses and significantly increases when taking ASA in high doses as a result of saturation of enzyme systems. Unlike other salicylates, when taking the drug repeatedly, non-hydrolyzed 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 at the used doses does not affect the bioavailability of acetylsalicylic acid.
Indications
Primary prophylaxis 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).
Prevention of recurrent myocardial infarction and blood vessel thrombosis.
Unstable angina pectoris.
Prevention of thromboembolism after vascular surgery (e.g. 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 salicylates and NSAIDs combination of bronchial asthma, nasal polyposis and paranasal sinus and gastrointestinal tract diseases in the exacerbation phase, gastrointestinal bleeding in the brain hemorrhage, tendency to bleed (thrombocytopenia, hemorrhagic diathesis, vitamin K deficiency) severe renal failure (creatinine clearance less than 30 ml / min) severe liver failure (more than 9 points on the Child-Pugh scale) pregnancy (I and III trimesters) breast-feeding period glucose-6-phosphate dehydrogenase deficiency concomitant use with methotrexate dose of 15 mg or more per week for children under 18 years of age (efficacy and safety not established).
Special instructions
ThromboMag ® should be used as directed by a doctor.
ASA can cause bronchospasm, cause attacks of bronchial asthma and other hypersensitivity reactions (see sections “Contraindications”, “With caution”). A history of bronchial asthma, hay fever, polyposis of the nose and paranasal sinuses, chronic respiratory diseases, as well as allergic reactions to other drugs (e.g. skin reactions, itching, urticaria) are risk factors.
The inhibitory effect of ASA on platelet aggregation persists for several days after administration, which should be considered during and after surgery. A few days before the planned surgical intervention, the risk of bleeding should be assessed in comparison with the risk of developing ischemic complications. With a significant risk of bleeding, the use of the drug TromboMag ® must be temporarily stopped (see section “With caution”).
In case of impaired renal function (creatinine clearance greater than 30 ml / min), as well as circulatory disorders resulting from atherosclerosis of the renal arteries, chronic heart failure, extensive surgery, sepsis, cases of massive bleeding, care should be taken, since in all of the above cases ASA may increase the risk of developing acute renal failure / impaired renal function (see the “Caution” section).
The risk of developing acute renal failure is known to increase with the combined use of other NSAIDs with ACE inhibitors or diuretics. Monitoring kidney function is recommended.
In patients with mild to moderate hepatic insufficiency, liver function should be regularly monitored (see section Precautions ).
The combined use of ASA and methotrexate is accompanied by an increase in the incidence of side effects from the hematopoietic organs, the combined use with valproic acid – an increased risk of its toxicity. During the first weeks of the combined use of the drug TromboMag ® and methotrexate at a dose of less than 15 mg per week, a blood test should be performed weekly. Careful monitoring must be carried out in the presence of even small impaired renal function, as well as in elderly patients (see sections “Contraindications”, “With caution”, “Interaction with other drugs”).
The combined use of ASA with anticoagulants, thrombolytic and antiplatelet drugs is associated with an increased risk of bleeding and damaging effects on the mucous membrane of the gastrointestinal tract (see sections “With caution”, “Interaction with other drugs”). The bleeding time should be monitored.
The combined use of the drug ThromboMag ® and ibuprofen is not recommended in patients with an increased risk of cardiovascular disease, since a decrease in the antiplatelet effect of ASA in doses up to 300 mg leads to a decrease in cardioprotective effects. Patients taking ibuprofen for pain relief should inform the doctor about this (see sections “With caution”, “Interaction with other drugs”).
Recommended monitoring of plasma concentrations of digoxin and lithium at the beginning or at the end of the joint use of the drug TromboMag ® may require dose adjustment (see section “With caution”, “Interaction with other drugs”).
With the combined use of systemic glucocorticosteroids (GCS) and ASA, the concentration of salicylates in the blood plasma is reduced, and after the cancellation of systemic GCS, an overdose of salicylates is possible. In addition, when used together, the risk of damage to the mucous membrane of the gastrointestinal tract and bleeding increases (see sections “With caution”, “Interaction with other drugs”).
With the combined use of ASA with diuretics and antihypertensive drugs (for example, ACE inhibitors), a possible decrease in their effectiveness should be taken into account (see section “Interaction with other drugs”).
Taking ASA in doses exceeding the recommended therapeutic (by patients of any age), or long-term administration of ASA in low doses (elderly patients) is associated with an increased risk of gastrointestinal bleeding. With prolonged use of the drug TromboMag ®, a general blood test and analysis of feces for occult blood, as well as the functional state of the liver, should be periodically monitored.
ASA in low doses reduces uric acid excretion and can provoke gout in susceptible patients with decreased uric acid excretion (see section Precautions, Interaction with other drugs ).
ASA in high doses has a hypoglycemic effect, which should be taken into account in patients with diabetes mellitus receiving hypoglycemic agents for oral administration or insulin (see section “With care”, “Interaction with other drugs”).
In severe forms of glucose-6-phosphate dehydrogenase deficiency, 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.
Composition
One tablet contains: active ingredients: acetylsalicylic acid 75 mg or 150 mg magnesium hydroxide 15.20 mg or 30.39 mg
excipients: corn starch 9.50 mg or 19.00 mg potato starch 2.00 mg or 4.00 mg microcrystalline cellulose 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.
Dosage and administration
Inside, 1-2 hours after a meal, 1 time per day.
The tablet of the ThromboMag ® preparation is swallowed whole (it can be chewed or crushed), washed down with water.
ThromboMag ® 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 (eg, diabetes, hyperlipidemia, hypertension, obesity, smoking, old age)
In the first day 1 tablet of the drug ThromboMag ®, containing 150 mg of acetylsalicylic acid, then 1 tablet of the TromboMag ® preparation containing 75 mg of acetylsalicylic acid.
Prevention of recurrent myocardial infarction and blood vessel thrombosis
1 tablet of the drug ThromboMag ® containing 75 mg or 150 mg of acetylsalicylic acid.
Unstable angina
1 tablet of the drug ThromboMag ® containing 75 mg or 150 mg of acetylsalicylic acid.
Prevention of thromboembolism after vascular surgery (eg, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty)
1 tablet of TromboMag ® containing 75 mg or 150 mg of acetylsalicylic acid.
If you miss one or more doses of TromboMag ®, you must take the missed dose immediately. as soon as the patient remembers this. To avoid doubling the dose, you should not take the missed tablet if the time for taking the next dose is approaching.
Peculiarities of action during the first administration or withdrawal of the drug were not observed.
Side effects of
In general, ThromboMag ®, which contains a low dose ASA and magnesium hydroxide antacid, is well tolerated.
The frequency of the following side effects is determined in accordance with the classification of the World Health Organization: very 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% or less 0.1% is very rare – less than 0.01%, including individual messages.
From the central nervous system: often – headache, insomnia infrequently – dizziness, drowsiness rarely – tinnitus, intracerebral hemorrhage.
From the hemopoietic system: very often – increased bleeding rarely – anemia very rarely – aplastic anemia, hypoprothrombinemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, agranulocytosis.
There are reports of cases of hemolysis and hemolytic anemia in patients with severe glucose-6-phosphate dehydrogenase deficiency.
From the respiratory system: often – bronchospasm.
From the digestive system: very often – heartburn often – nausea, vomiting infrequently – pain in the abdomen, ulcers of the mucous membrane of the stomach and duodenum, including perforating (rarely), gastrointestinal bleeding rarely – increased activity of the ² Ñliver ² Ñ enzymes are very rare – stomatitis, esophagitis, erosive lesions of the upper gastrointestinal tract (including with strictures), colitis, irritable bowel syndrome.
Allergic reactions: infrequently – urticaria, Quincke’s edema, skin rash, itching, rhinitis, edema of the nasal mucosa very rarely – anaphylactic shock, cardiorespiratory distress syndrome.
Other: very rare – impaired renal function.
Overdose of
Early signs of an overdose of salicylates (salicylism) include tinnitus / ringing and develop at a plasma concentration of about 200 mcg / ml. Are severe toxic effects associated with salicylate concentrations? 400 mcg / ml.
Symptoms of an overdose of moderate severity: nausea, vomiting, tinnitus, hearing loss, dizziness, confusion.
Treatment: gastric lavage, repeated use of activated charcoal symptomatic therapy.
Symptoms of a severe overdose: fever, hyperventilation, ketoacidosis, respiratory alkalosis, severe hypoglycemia, cardiovascular and respiratory failure, coma.
Treatment: Immediate hospitalization in a specialized department for emergency treatment (gastric lavage, repeated use of activated carbon, alkaline and forced alkaline diuresis, hemodialysis, restoration of water-electrolyte and acid-base state, symptomatic therapy). When carrying out alkaline diuresis, it is necessary to achieve a urine pH value in 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. An overdose is especially dangerous in elderly patients.
Storage conditions
In a place protected from moisture and light at a temperature not exceeding 25 ° C.
Keep out of the reach of children!
Expiration
5 years.
Terms and conditions
without prescription
Dosage
capsule form
