Thrombosten (Tablets) Instructions for Use

Marketing Authorization Holder

Atoll LLC (Russia)

Manufactured By

Ozon, LLC (Russia)

ATC Code

B01AC06 (Acetylsalicylic acid)

Active Substance

Acetylsalicylic acid (Ph.Eur. European Pharmacopoeia)

Dosage Forms

	Thrombosten	Enteric-coated film-coated tablets, 50 mg: 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 100, 120, 125, 150, 180, 250 or 300 pcs.
		Enteric-coated film-coated tablets, 100 mg: 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 100, 120, 125, 150, 180, 250 or 300 pcs.
		Enteric-coated film-coated tablets, 300 mg: 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 100, 120, 125, 150, 180, 250 or 300 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated film-coated tablets white, round, biconvex; the core on the cross-section is white or almost white.

Excipients: microcrystalline cellulose (MCC-102) – 39.3 mg, low-substituted hydroxypropyl cellulose – 4.75 mg, stearic acid – 0.95 mg.

Coating composition ACRYL-EZE^® 93A18597 white – 7.2 mg, incl.: methacrylic acid and ethyl acrylate copolymer [1:1] – 4.752 mg, talc – 1.188 mg, titanium dioxide – 1.08 mg, colloidal silicon dioxide – 0.072 mg, sodium bicarbonate – 0.072 mg, sodium lauryl sulfate – 0.036 mg.
Triethyl citrate – 0.8 mg, polyvinyl alcohol – 0.75 mg, macrogol-4000 – 0.25 mg.

5 pcs. – contour cell blisters (1) – cardboard packs.
5 pcs. – contour cell blisters (2) – cardboard packs.
5 pcs. – contour cell blisters (3) – cardboard packs.
5 pcs. – contour cell blisters (4) – cardboard packs.
5 pcs. – contour cell blisters (5) – cardboard packs.
5 pcs. – contour cell blisters (6) – cardboard packs.
5 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
10 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (5) – cardboard packs.
10 pcs. – contour cell blisters (6) – cardboard packs.
10 pcs. – contour cell blisters (10) – cardboard packs.
25 pcs. – contour cell blisters (1) – cardboard packs.
25 pcs. – contour cell blisters (2) – cardboard packs.
25 pcs. – contour cell blisters (3) – cardboard packs.
25 pcs. – contour cell blisters (4) – cardboard packs.
25 pcs. – contour cell blisters (5) – cardboard packs.
25 pcs. – contour cell blisters (6) – cardboard packs.
25 pcs. – contour cell blisters (10) – cardboard packs.
30 pcs. – contour cell blisters (1) – cardboard packs.
30 pcs. – contour cell blisters (2) – cardboard packs.
30 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – contour cell blisters (4) – cardboard packs.
30 pcs. – contour cell blisters (5) – cardboard packs.
30 pcs. – contour cell blisters (6) – cardboard packs.
30 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – bottles (1) – cardboard packs.
20 pcs. – bottles (1) – cardboard packs.
30 pcs. – bottles (1) – cardboard packs.
50 pcs. – bottles (1) – cardboard packs.
60 pcs. – bottles (1) – cardboard packs.
100 pcs. – bottles (1) – cardboard packs.

Enteric-coated film-coated tablets white, round, biconvex; the core on the cross-section is white or almost white.

Excipients: microcrystalline cellulose (MCC-102) – 78.6 mg, low-substituted hydroxypropyl cellulose – 9.5 mg, stearic acid – 1.9 mg.

Coating composition ACRYL-EZE^® 93A18597 white – 14 mg, incl.: methacrylic acid and ethyl acrylate copolymer [1:1] – 9.504 mg, talc – 2.376 mg, titanium dioxide – 2.16 mg, colloidal silicon dioxide – 0.144 mg, sodium bicarbonate – 0.144 mg, sodium lauryl sulfate – 0.072 mg.
Triethyl citrate – 1.6 mg, polyvinyl alcohol – 1.5 mg, macrogol-4000 – 0.5 mg.

5 pcs. – contour cell blisters (1) – cardboard packs.
5 pcs. – contour cell blisters (2) – cardboard packs.
5 pcs. – contour cell blisters (3) – cardboard packs.
5 pcs. – contour cell blisters (4) – cardboard packs.
5 pcs. – contour cell blisters (5) – cardboard packs.
5 pcs. – contour cell blisters (6) – cardboard packs.
5 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
10 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (5) – cardboard packs.
10 pcs. – contour cell blisters (6) – cardboard packs.
10 pcs. – contour cell blisters (10) – cardboard packs.
25 pcs. – contour cell blisters (1) – cardboard packs.
25 pcs. – contour cell blisters (2) – cardboard packs.
25 pcs. – contour cell blisters (3) – cardboard packs.
25 pcs. – contour cell blisters (4) – cardboard packs.
25 pcs. – contour cell blisters (5) – cardboard packs.
25 pcs. – contour cell blisters (6) – cardboard packs.
25 pcs. – contour cell blisters (10) – cardboard packs.
30 pcs. – contour cell blisters (1) – cardboard packs.
30 pcs. – contour cell blisters (2) – cardboard packs.
30 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – contour cell blisters (4) – cardboard packs.
30 pcs. – contour cell blisters (5) – cardboard packs.
30 pcs. – contour cell blisters (6) – cardboard packs.
30 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – bottles (1) – cardboard packs.
20 pcs. – bottles (1) – cardboard packs.
30 pcs. – bottles (1) – cardboard packs.
50 pcs. – bottles (1) – cardboard packs.
60 pcs. – bottles (1) – cardboard packs.
100 pcs. – bottles (1) – cardboard packs.

Enteric-coated film-coated tablets white, round, biconvex; the core on the cross-section is white or almost white.

Excipients: microcrystalline cellulose (MCC-102) – 235.8 mg, low-substituted hydroxypropyl cellulose – 28.5 mg, stearic acid – 5.7 mg.

Coating composition ACRYL-EZE^® 93A18597 white – 43.2 mg, incl.: methacrylic acid and ethyl acrylate copolymer [1:1] – 28.512 mg, talc – 7.128 mg, titanium dioxide – 6.48 mg, colloidal silicon dioxide – 0.432 mg, sodium bicarbonate – 0.432 mg, sodium lauryl sulfate – 0.216 mg.
Triethyl citrate – 4.8 mg, polyvinyl alcohol – 4.5 mg, macrogol-4000 – 1.5 mg.

5 pcs. – contour cell blisters (1) – cardboard packs.
5 pcs. – contour cell blisters (2) – cardboard packs.
5 pcs. – contour cell blisters (3) – cardboard packs.
5 pcs. – contour cell blisters (4) – cardboard packs.
5 pcs. – contour cell blisters (5) – cardboard packs.
5 pcs. – contour cell blisters (6) – cardboard packs.
5 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
10 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (5) – cardboard packs.
10 pcs. – contour cell blisters (6) – cardboard packs.
10 pcs. – contour cell blisters (10) – cardboard packs.
25 pcs. – contour cell blisters (1) – cardboard packs.
25 pcs. – contour cell blisters (2) – cardboard packs.
25 pcs. – contour cell blisters (3) – cardboard packs.
25 pcs. – contour cell blisters (4) – cardboard packs.
25 pcs. – contour cell blisters (5) – cardboard packs.
25 pcs. – contour cell blisters (6) – cardboard packs.
25 pcs. – contour cell blisters (10) – cardboard packs.
30 pcs. – contour cell blisters (1) – cardboard packs.
30 pcs. – contour cell blisters (2) – cardboard packs.
30 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – contour cell blisters (4) – cardboard packs.
30 pcs. – contour cell blisters (5) – cardboard packs.
30 pcs. – contour cell blisters (6) – cardboard packs.
30 pcs. – contour cell blisters (10) – cardboard packs.
10 pcs. – bottles (1) – cardboard packs.
20 pcs. – bottles (1) – cardboard packs.
30 pcs. – bottles (1) – cardboard packs.
50 pcs. – bottles (1) – cardboard packs.
60 pcs. – bottles (1) – cardboard packs.
100 pcs. – bottles (1) – cardboard packs.

Clinical-Pharmacological Group

NSAID. Antiplatelet agent

Pharmacotherapeutic Group

Antithrombotic agents; antiplatelet agents, other than heparin

Pharmacological Action

NSAID, antiplatelet agent. The mechanism of action of acetylsalicylic acid is based on the irreversible inhibition of the COX-1 enzyme, resulting in blocked synthesis of thromboxane A₂ and suppressed platelet aggregation. It is believed that acetylsalicylic acid has other mechanisms for suppressing platelet aggregation, which expands its scope of application in various vascular diseases.

Acetylsalicylic acid in higher doses also has anti-inflammatory, analgesic, and antipyretic effects.

Pharmacokinetics

When taken orally, it is rapidly absorbed mainly from the proximal part of the small intestine and to a lesser extent from the stomach. The presence of food in the stomach significantly alters the absorption of acetylsalicylic acid. The bioavailability of acetylsalicylic acid is about 70%, but this value is characterized by significant individual variability due to presystemic hydrolysis in the mucous membranes of the gastrointestinal tract and in the liver with the formation of salicylic acid under the action of enzymes. The bioavailability of salicylic acid is 80-100%. It is metabolized in the liver by hydrolysis to form salicylic acid followed by conjugation with glycine or glucuronide. The concentration of salicylates in blood plasma is variable.

About 80% of salicylic acid binds to plasma proteins. Salicylates easily penetrate into many tissues and body fluids, including cerebrospinal, peritoneal, and synovial fluids. Salicylates are found in small amounts in brain tissue, traces are found in bile, sweat, and feces. It quickly crosses the placental barrier and is excreted in small amounts in breast milk.

It is excreted mainly by active secretion in the renal tubules unchanged (60%) and in the form of metabolites. The excretion of unchanged salicylate depends on the pH of the urine (when the urine is alkalized, the ionization of salicylates increases, their reabsorption worsens, and excretion increases significantly). The T_1/2 of acetylsalicylic acid is approximately 15 min. The T_1/2 of salicylate when taken in low doses is 2-3 hours; with an increase in dose (>3 g), it can increase to 15-30 hours due to saturation of enzyme systems.

Indications

Unstable angina and stable angina; prevention of recurrent myocardial infarction; prevention of recurrent transient ischemic attack and recurrent ischemic stroke in patients who have previously suffered a cerebrovascular accident; prevention of thrombotic complications after surgery and invasive interventions on blood vessels (such as coronary artery bypass grafting, carotid endarterectomy, arteriovenous shunting, coronary artery angioplasty and stenting, carotid artery angioplasty).

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific clinical indication and patient risk factors.

For secondary prevention of myocardial infarction, administer a single daily dose of 50 mg to 100 mg.

For the management of unstable angina, use a single daily dose of 100 mg to 200 mg, or administer 100 mg once daily.

For the prevention of recurrent ischemic stroke and transient ischemic attack, prescribe a daily dose of 100 mg to 300 mg.

To prevent thrombotic complications after vascular surgery (e.g., coronary artery bypass grafting, carotid endarterectomy, angioplasty with stenting), use a daily dose of 100 mg to 300 mg.

Swallow the enteric-coated tablet whole with a sufficient amount of water. Do not crush or chew the tablet.

Take the dose once daily, preferably at the same time each day. Administration can occur with or without food, but consistent timing is recommended.

For long-term antiplatelet therapy, the most common maintenance dose is 75 mg to 100 mg once daily.

Do not use in children and adolescents under the age of 18 years.

Adverse Reactions

Allergic reactions often – urticaria, angioedema; sometimes – anaphylactic reactions.

From the digestive system very often – heartburn; often – nausea, vomiting; sometimes – abdominal pain, ulcers of the gastric and duodenal mucosa, gastrointestinal bleeding; rarely – perforation of gastric or duodenal ulcer, increased activity of liver enzymes; very rarely – stomatitis, esophagitis, erosive lesions of the upper gastrointestinal tract, strictures, colitis, irritable bowel syndrome.

From the respiratory system often – bronchospasm.

From the hematopoietic system very often – increased bleeding; rarely – anemia; very rarely – hypoprothrombinemia, thrombocytopenia, neutropenia, aplastic anemia, eosinophilia, agranulocytosis.

From the nervous system sometimes – dizziness, drowsiness; often – headache, insomnia; rarely – tinnitus, cerebral hemorrhage.

Contraindications

Cerebral hemorrhage; tendency to bleeding (vitamin K deficiency, thrombocytopenia, hemorrhagic diathesis); bronchial asthma induced by the intake of salicylates and NSAIDs; erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase); gastrointestinal bleeding; severe renal failure (creatinine clearance <10 ml/min); glucose-6-phosphate dehydrogenase deficiency; simultaneous use with methotrexate (>15 mg per week); I and III trimesters of pregnancy; lactation period (breastfeeding); children and adolescents under 18 years of age; hypersensitivity to acetylsalicylic acid and other NSAIDs.

With caution

Gout, hyperuricemia, history of ulcerative lesions of the gastrointestinal tract or gastrointestinal bleeding, renal and/or hepatic insufficiency, bronchial asthma, hay fever, nasal polyposis, allergic conditions, II trimester of pregnancy.

Use in Pregnancy and Lactation

Contraindicated for use in the I and III trimesters of pregnancy. In the II trimester of pregnancy, a single dose is possible for strict indications.

It has a teratogenic effect: when used in the I trimester, it leads to the development of cleft palate; in the III trimester, it causes inhibition of labor (inhibition of prostaglandin synthesis), premature closure of the arterial duct in the fetus, hyperplasia of the pulmonary vessels and hypertension in the pulmonary circulation.

Acetylsalicylic acid is excreted in breast milk, which increases the risk of bleeding in the child due to impaired platelet function, therefore acetylsalicylic acid should not be used by the mother during lactation.

Use in Hepatic Impairment

Contraindication: hepatic insufficiency.

Use with caution in patients with liver diseases.

Use in Renal Impairment

Contraindication: renal failure.

Use with caution in patients with kidney diseases.

Pediatric Use

Contraindication: children and adolescents under 18 years of age.

Geriatric Use

Use with caution to avoid the risk of exacerbation of chronic diseases.

Special Precautions

Acetylsalicylic acid can provoke bronchospasm, as well as cause attacks of bronchial asthma and other hypersensitivity reactions. Risk factors are a history of bronchial asthma, hay fever, nasal polyposis, chronic respiratory diseases, as well as allergic reactions (for example, skin reactions, itching, urticaria) to other drugs.

Acetylsalicylic acid can cause bleeding of varying severity during and after surgical interventions.

Several days before a planned surgical intervention, the risk of bleeding should be assessed against the risk of ischemic complications in patients taking low doses of acetylsalicylic acid. If the risk of bleeding is significant, the intake of acetylsalicylic acid should be temporarily discontinued.

The combination of acetylsalicylic acid with anticoagulants, thrombolytics and antiplatelet drugs is accompanied by an increased risk of bleeding.

Taking acetylsalicylic acid in low doses can provoke the development of gout in predisposed individuals (with reduced excretion of uric acid).

The combination of acetylsalicylic acid with methotrexate is accompanied by an increased frequency of side effects from the hematopoietic organs.

Taking acetylsalicylic acid in high doses has a hypoglycemic effect, which should be taken into account when prescribing it to patients with diabetes mellitus receiving oral hypoglycemic agents and insulin.

When using systemic corticosteroids and salicylates concomitantly, it should be remembered that during treatment the concentration of salicylates in the blood is reduced, and after discontinuation of systemic corticosteroids, an overdose of salicylates is possible.

The combination of acetylsalicylic acid with ibuprofen is not recommended in patients with an increased risk of cardiovascular diseases: when used concomitantly with ibuprofen, a decrease in the antiplatelet effect of acetylsalicylic acid in doses up to 300 mg is noted, which leads to a reduction in the cardioprotective effects of acetylsalicylic acid.

Exceeding the dose of acetylsalicylic acid beyond the recommended therapeutic doses is associated with a risk of gastrointestinal bleeding.

When using acetylsalicylic acid in low doses long-term as antiplatelet therapy, caution is necessary in elderly patients due to the risk of gastrointestinal bleeding.

Concomitant use of acetylsalicylic acid with ethanol increases the risk of damage to the gastrointestinal mucosa and prolongation of bleeding time.

Effect on the ability to drive vehicles and operate machinery

During treatment with acetylsalicylic acid preparations, patients should exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Concomitant use of antacids containing magnesium and/or aluminum hydroxide slows down and reduces the absorption of acetylsalicylic acid.

Concomitant use with calcium channel blockers, agents that limit calcium intake or increase calcium excretion from the body, increases the risk of bleeding.

Concomitant use with acetylsalicylic acid enhances the effects of heparin and indirect anticoagulants, hypoglycemic agents of the sulfonylurea derivatives, insulins, methotrexate, phenytoin, valproic acid.

Concomitant use with glucocorticoids increases the risk of ulcerogenic action and the occurrence of gastrointestinal bleeding.

Concomitant use reduces the effectiveness of diuretics (spironolactone, furosemide).

Concomitant use of other NSAIDs increases the risk of adverse effects. Acetylsalicylic acid may reduce plasma concentrations of indomethacin, piroxicam.

Concomitant use with gold preparations, Acetylsalicylic acid may induce liver damage.

Concomitant use reduces the effectiveness of uricosuric agents (including probenecid, sulfinpyrazone, benzbromarone).

Concomitant use of acetylsalicylic acid and alendronate sodium may lead to the development of severe esophagitis.

Concomitant use with griseofulvin may impair the absorption of acetylsalicylic acid.

A case of spontaneous iris hemorrhage has been described with the intake of Ginkgo biloba extract against the background of long-term use of acetylsalicylic acid at a dose of 325 mg/day. It is believed that this may be due to an additive inhibitory effect on platelet aggregation.

Concomitant use with dipyridamole may increase the C_max of salicylate in blood plasma and AUC.

Concomitant use with acetylsalicylic acid increases the plasma concentrations of digoxin, barbiturates, and lithium salts.

Concomitant use of high-dose salicylates with carbonic anhydrase inhibitors may lead to salicylate intoxication.

Acetylsalicylic acid in doses less than 300 mg/day has a slight effect on the effectiveness of captopril and enalapril. When using acetylsalicylic acid in high doses, a decrease in the effectiveness of captopril and enalapril is possible.

Concomitant use with caffeine increases the rate of absorption, plasma concentration, and bioavailability of acetylsalicylic acid.

Concomitant use, metoprolol may increase the C_max of salicylate in blood plasma.

When using pentazocine against the background of long-term use of high doses of acetylsalicylic acid, there is a risk of severe adverse renal reactions.

Concomitant use, phenylbutazone reduces the uricosuria caused by acetylsalicylic acid.

Concomitant use, ethanol may enhance the effect of acetylsalicylic acid on the gastrointestinal tract.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.