Instructions for use of TROMBO ASS® (THROMBO ASS)

MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION INSTRUCTIONS for the use of the drug for medical use Thrombo ACC®

Registration number:

P N013722/01
Trade name:
Thrombo ACC®
Group name:
acetylsalicylic acid
Dosage form:
enteric tablets, film-coated
Description:
Round, biconvex tablets, white, film-coated.
The surface of the tablet is smooth or slightly rough, shiny. Pharmacotherapeutic group:
antiplatelet agent.
ATX code:
B01AC06

pharmachologic effect

Pharmacodynamics

Acetylsalicylic acid (ASA) is an ester of salicylic acid and belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action is based on irreversible inhibition of the enzyme cyclooxygenase (COX-1), as a result of which the synthesis of prostaglandins, prostacyclins and thromboxane is blocked. Reduces platelet aggregation, adhesion and thrombus formation by suppressing the synthesis of thromboxane A2 in platelets. The antiplatelet effect is most pronounced in platelets, since they are unable to re-synthesize cyclooxygenase. The antiplatelet effect develops after the use 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, coronary heart disease, and complications of varicose veins.

Increases the fibrinolytic activity of blood plasma and reduces the concentration of vitamin K-dependent coagulation factors (II, VII, IX, X). ASA also has anti-inflammatory, antipyretic and analgesic effects.

Pharmacokinetics

Absorption
After oral administration, ASA is quickly and completely absorbed from the gastrointestinal tract (GIT). Thrombo ACC® tablets are enteric-coated, which reduces the direct irritant effect of ASA on the gastric mucosa.

The maximum concentration of acetylsalicylic acid in the blood plasma (Cmax) is reached approximately 2-7 hours after taking the tablets, thus, the absorption of ASA in the form of enteric-soluble film-coated tablets is slowed down compared to conventional tablets (without enteric coating).

When taken simultaneously with food, a slowdown in the absorption of ASA is observed without affecting the degree of absorption. The lower rate of absorption of enteric-coated ASA tablets does not affect the exposure of ASA in the blood plasma and its ability to inhibit platelet aggregation during long-term therapy with low doses of the drug. However, to ensure maximum stability of ASA tablets in the stomach, it is recommended to take the drug 30 minutes before meals with plenty of liquid (see section “Dosage and Administration”).

Metabolism

ASA is partially metabolized during absorption. During and after absorption, ASA is converted to the main metabolite, salicylic acid, which is metabolized mainly in the liver under the influence of liver enzymes to form salicyrulic acid, phenolic salicylic acid glucuronide, salicyl glucuronide and gentisuric acid.

In women, the metabolic process is slower (less enzyme activity in the blood serum).

Distribution

ASA and salicylic acid are highly bound to plasma proteins (from 49 to 70% for ASA; from 66 to 98% for salicylic acid, respectively, depending on the dose) and are quickly distributed in the body. After oral administration of ASA, salicylic acid crosses the placenta and is excreted in breast milk.

Removal

The elimination of salicylic acid is dose-dependent, since its metabolism is limited by the capabilities of the enzymatic system. The half-life ranges from 2-3 hours when using ASA in low doses and up to 15 hours when using the drug in high doses (usual doses of acetylsalicylic acid as an analgesic). Salicylic acid and its metabolites are excreted by the kidneys.

Unlike other salicylates, with repeated administration of the drug, non-hydrolyzed ASA does not accumulate in the blood serum.

In patients with normal renal function, 80-100% of a single dose of the drug is excreted by the kidneys within 24-72 hours.

Indications for use

• Prevention of recurrent myocardial infarction;
• Unstable angina) and stable angina;
• Prevention of recurrent ischemic stroke in patients who previously suffered a cerebrovascular accident;
• Prevention of recurrent transient ischemic attack (TIA);
• Prevention of thrombotic complications after surgery and invasive vascular interventions (for example, coronary artery bypass grafting, carotid endarterectomy, arteriovenous bypass, angioplasty and stenting of the coronary arteries, carotid angioplasty).

Contraindications

• Hypersensitivity to acetylsalicylic acid, excipients in the drug or NSAIDs;
• Erosive and ulcerative lesions of the gastrointestinal tract (in the acute stage);
• Gastrointestinal bleeding;
• Hemorrhagic diathesis, thrombocytopenia, hemophilia;
• Bronchial asthma induced by taking salicylates and other NSAIDs, a combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to ASA;
• Combined use with methotrexate at a dose of 15 mg per week or more;
• Pregnancy (I and III trimester) and breastfeeding period;
• Children and adolescents under 18 years of age (no data on effectiveness and safety);
• Severe renal impairment;
• Severe liver dysfunction;
• Chronic heart failure III-IV functional class according to the NYHA classification;
• Lactose intolerance, lactase deficiency and glucose-galactose malabsorption;
• Hyperoxaluria.

Carefully

• For gout, hyperuricemia, since ASA in low doses reduces the excretion of uric acid, which in turn can provoke an attack of gout in predisposed patients.
• A history of ulcerative lesions of the gastrointestinal tract, including chronic and recurrent lesions of the gastrointestinal tract or a history of gastrointestinal bleeding.
• If liver function is impaired (below class B according to the Child-Pugh classification).
• If renal function is impaired (creatinine clearance more than 30 ml/min).
• For bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis, as well as allergic reactions (skin reactions, itching, urticaria) to other drugs, including NSAIDs (analgesics, anti-inflammatory, antirheumatic drugs).
• For circulatory disorders resulting from atherosclerosis of the renal arteries, congestive heart failure, hypovolemia, extensive surgery, sepsis, cases of massive bleeding.
• In the second trimester of pregnancy.
• In severe forms of glucose-b-phosphate dehydrogenase deficiency.
• For proposed surgery (including minor ones, such as tooth extraction).
• When used in combination with the following drugs (see section “Interaction with other drugs”): with methotrexate at a dose of less than 15 mg per week;
• with anticoagulants, thrombolytic or other antiplatelet drugs;
• with NSAIDs (including ibuprofen, naproxen);
• with digoxin;
• with hypoglycemic drugs for oral administration (sulfonylurea derivatives) and insulin;
• with valproic acid;
• with alcohol (alcoholic drinks, in particular);
• with selective serotonin reuptake inhibitors.

Use during pregnancy

Use during pregnancy
Inhibition of prostaglandin synthesis may have a negative effect on pregnancy and the development of the embryo or fetus.

Data from epidemiological studies on the use of prostaglandin synthesis inhibitors in early pregnancy indicate an increased risk of miscarriage and the development of congenital malformations of the fetus (including heart defects, cleft palate, as well as an increased risk of developing gastroschisis, presumably increasing with increasing doses of the drug and duration of treatment.

Animal studies have demonstrated the reproductive toxicity of acetylsalicylic acid. In the first trimester of pregnancy, the use of drugs containing acetylsalicylic acid is contraindicated.

In the second trimester of pregnancy, salicylates can be prescribed only taking into account a strict assessment of the risks and benefits for the mother and fetus.

Women planning pregnancy or in the second trimester of pregnancy should reduce the dose of acetylsalicylic acid and the duration of treatment as much as possible.

In the third trimester of pregnancy, prostaglandin synthesis inhibitors can cause suppression of uterine contractions, leading to inhibition of labor, an increase in bleeding time and an increase in the antiplatelet effect (even when using acetylsalicylic acid in low doses).

The fetus may develop cardiopulmonary intoxication with premature closure of the ductus arteriosus and the development of pulmonary hypertension, as well as impaired renal function, up to the development of renal failure, accompanied by oligohydramnios. The use of acetylsalicylic acid in the third trimester of pregnancy is contraindicated.

Use during breastfeeding

Salicylates and their metabolites pass into breast milk in small quantities. Occasional intake of salicylates during breastfeeding is not accompanied by the development of adverse reactions in the child and does not require cessation of breastfeeding. However, with long-term use of the drug or when it is prescribed in a high dose, breastfeeding should be stopped immediately.

Instructions for use of TROMBO ASS® (THROMBO ASS)

The drug should be prescribed with caution in the following conditions:

• with known hypersensitivity to other analgesics/anti-inflammatory drugs/anti-rheumatic drugs;
• if you have other types of allergies (for example, skin reactions, itching, urticaria);
• for bronchial asthma, hay fever, changes in the nasal mucosa (nasal polyps), chronic respiratory diseases;
• with simultaneous therapy with medications that prevent blood clotting (for example, coumarin derivatives, heparin, with the exception of therapy using small doses of heparin);
• with genetically determined deficiency of glucose-6-phosphate dehydrogenase (hemolytic anemia);
• for pain in the stomach and intestines, gastritis;
• with a history of stomach and intestinal ulcers or bleeding in the gastrointestinal tract;
• with impaired liver and/or kidney function.

Before the planned operation (also for minor interventions, for example dental operations), the doctor performing the operation must be informed about the use of Thrombo ACC®, so that the doctor takes into account the platelet aggregation suppressing effect of acetylsalicylic acid. This effect may result in increased bleeding time.

Additional use of other salicylates or NSAIDs/anti-rheumatic drugs is contraindicated.

If acetylsalicylic acid is taken for several years, kidney function may be impaired. Kidney function should be monitored regularly.

Patients prescribed thrombolytic therapy should be monitored for symptoms of external or internal bleeding.

Acetylsalicylic acid at low dosages prevents the excretion of uric acid. In patients with certain diagnoses, this can lead to gout attacks.

Children and teenagers with febrile illnesses should take acetylsalicylic acid only with a doctor's prescription or only if other options do not work. In some cases, life-threatening complications (Reye's syndrome) were observed in children and adolescents. In case of prolonged vomiting, dehydration, clouding of consciousness and convulsions, immediate intensive care is required. A causal relationship with certain medications has not yet been proven.

The drug contains lactose. Patients with rare hereditary galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption should not take this drug.

Preclinical safety data

Preclinical test results were obtained from oral, nasal, subcutaneous and intravenous administration in mice, rats, guinea pigs, rabbits and dogs. During chronic toxicity testing, no significant changes were observed at human dosages compared to controls.

Acetylsalicylic acid has not shown any mutagenic potential in laboratory studies.

Experiments on mice and rats showed no evidence of the carcinogenic potential of acetylsalicylic acid.

As part of an experiment on animals (rats, dogs), teratogenic effects were discovered when using large doses of acetylsalicylic acid.

Impact on the ability to drive vehicles and operate machinery

No special studies have been conducted on this matter. Based on pharmacodynamic properties and side effects, no effect on the ability to drive vehicles or operate machinery was noted.

Directions for use and doses

Inside.

It is advisable to take Thrombo ACC® tablets at least 30 minutes before meals with plenty of water. To ensure the release of ASA in the alkaline environment of the duodenum, the tablets should not be broken, crushed or chewed. Thrombo ACC® tablets are taken once a day or every other day. Trombo ACC® is intended for long-term use.

The duration of therapy is determined by the doctor.

Prevention of recurrent infarction, stable and unstable angina:

100-300 mg/day.

Prevention of recurrent ischemic stroke and recurrent transient ischemic attack (TIA):

100-300 mg/day.

Prevention of thrombotic complications after operations and invasive interventions on blood vessels:

100-300 mg/day.

What to do if you miss one or more doses of the drug:

Take the missed pill as soon as you remember, and then continue taking it as usual. To avoid doubling the dose, do not take the missed tablet if it is near the time of your next tablet.

Features of the action of the drug when first taken and when discontinued:

No specific effects of the drug were observed during the first dose or its withdrawal.

Special patient groups - children

The safety and effectiveness of using Thrombo ACC® in children and adolescents under 18 years of age has not been established. The use of the drug in patients under 18 years of age is contraindicated.

Patients with liver dysfunction

Thrombo ACC® is contraindicated in patients with severe liver dysfunction. Thrombo ACC® should be used with caution in patients with impaired liver function.

Patients with impaired renal function

Thrombo ACC® is contraindicated in patients with severe renal impairment. Thrombo ACC® should be used with caution in patients with impaired renal function, since taking the drug may increase the risk of developing renal failure and acute renal failure (see section "Special Instructions").

Side effect

The frequency of occurrence of adverse reactions is classified in accordance with the recommendations of the World Health Organization (WHO), side effects are classified by frequency:

very often (≥ 1/10), often (≥ 1/100 and ˂ 1/10), infrequently (≥ 1/1000 and ˂ 1/100), rarely (≥ 1/10000 and ˂ 1/1000), very rarely (˂ 1/10000), frequency unknown (cannot be estimated from available data).

Adverse reactions also include data that were obtained from monitoring patients with rheumatic disorders who received high doses of ASA over an extended period of time.

ASA can lead to complaints of abdominal pain, the development of gastric and duodenal ulcers, and erosive gastritis, which can lead to serious gastrointestinal bleeding. The likelihood of these effects occurring increases with higher doses, although it is possible that they may occur at lower doses. If ASA is used for a long period of time, gastrointestinal bleeding may lead to the development of acute or chronic post-hemorrhagic/iron deficiency anemia.

Edema, hypertension, and heart failure have also been reported with NSAID therapy.

If you experience the side effects listed in the instructions, or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

In case of overdose, you should immediately consult a doctor.

Salicylate intoxication (develops when taking ASA at a dose of more than 100 mg/kg/day for more than 2 days) can result from prolonged use of toxic doses of the drug as part of improper therapeutic use of the drug (chronic intoxication) or a single accidental or intentional intake of a toxic dose of the drug adults or children (acute intoxication).

Symptoms of chronic intoxication with salicylic acid derivatives are nonspecific and are often difficult to diagnose. Mild intoxication usually develops only after repeated use of large doses of the drug and is manifested by dizziness, vertigo, tinnitus, hearing loss, increased sweating, nausea and vomiting, headache and confusion. These symptoms disappear after reducing the dose of the drug. Tinnitus may appear when the concentration of ASA in the blood plasma is from 150 to 300 mcg/ml. More severe symptoms appear when plasma ASA concentrations are above 300 mcg/ml.

The main manifestation of acute intoxication is a severe disturbance of the acid-base state, the manifestations of which may vary depending on the age of the patient and the severity of intoxication. In children, the most typical development is metabolic acidosis. Since the rate of absorption of ASA may be reduced due to delayed gastric emptying, the formation of stones, or the use of drugs resistant to the action of gastrointestinal juice, the severity of intoxication cannot be judged solely by changes in the concentration of salicylates in the blood plasma. Treatment of intoxication is carried out in accordance with accepted standards and depends on the severity of intoxication and the clinical picture and should be aimed mainly at accelerating the elimination of the drug and restoring the water-electrolyte balance and acid-base state.

Symptoms of overdose:
- for mild to moderate severity (single dose less than 150 mg/kg): dizziness, tinnitus, hearing loss, increased sweating, nausea and vomiting, headache, confusion, profuse sweating, tachypnea, hyperventilation, respiratory alkalosis. Treatment:
gastric lavage, repeated intake of activated carbon, forced alkaline diuresis, restoration of water-electrolyte balance and acid-base state.
- for moderate and 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;
• respiratory disorders, hyperventilation, non-cardiogenic pulmonary edema, respiratory depression, asphyxia;
• from the cardiovascular system:
  heart rhythm disturbances, arterial hypotension, cardiac depression;
• from the water-electrolyte balance:
  dehydration, impaired renal function from oliguria up to the development of renal failure, characterized by hypokalemia, hypernatremia, hyponatremia;
• impaired glucose metabolism: hyperglycemia, hypoglycemia (especially in children), ketoacidosis;
• tinnitus, 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 treatment - gastric lavage, repeated intake of activated charcoal, forced alkaline diuresis, hemodialysis, restoration of water-electrolyte balance and acid-base state, symptomatic therapy.

Interaction with other drugs

When used simultaneously, ASA enhances the effect of the following medications:

• methotrexate by reducing renal clearance and displacing it from protein binding; the use of the drug Thrombo ACC® together with methotrexate is contraindicated if the dose of the latter exceeds 15 mg per week (see section “Contraindications”) and can be used with caution when the dose of methotrexate is less than 15 mg per week;
• heparin and indirect anticoagulants due to disruption of platelet function and displacement of indirect anticoagulants from binding with proteins;
• when used simultaneously with anticoagulants, thrombolytic and antiplatelet agents, there is an increase in the risk of bleeding as a result of the synergism of the main therapeutic effects of the drugs used;
• when used simultaneously with drugs that have anticoagulant, thrombolytic or antiplatelet effects, an increased damaging effect on the mucous membrane of the gastrointestinal tract is observed;
• selective serotonin reuptake inhibitors, which may lead to an increased risk of bleeding from the upper gastrointestinal tract (synergism with ASA);
• digoxin due to a decrease in its renal excretion, which can lead to an overdose;
• hypoglycemic drugs (insulin, sulfonylurea derivatives) due to the hypoglycemic properties of ASA itself in high doses and displacing sulfonylurea derivatives from association with blood plasma proteins;
• when used simultaneously with valproic acid, its toxicity increases due to displacement from the connection with blood plasma proteins;
• NSAIDs (increased risk of ulcerogenic effect and bleeding from the gastrointestinal tract as a result of synergistic action);
• Ethanol (alcoholic beverages) (increased risk of damage to the mucous membrane of the gastrointestinal tract and prolongation of bleeding time as a result of the mutual enhancement of the effects of ASA and ethanol).

Simultaneous administration of ASA in high doses may weaken the effect of the following drugs:

• any diuretics (when used together with ASA in high doses, a decrease in glomerular filtration rate is observed as a result of a decrease in the synthesis of prostaglandins in the kidneys);
• angiotensin-converting enzyme (ACE) inhibitors (a dose-dependent decrease in glomerular filtration rate (GFR) is noted as a result of inhibition of prostaglandins that have a vasodilatory effect, respectively, a weakening of the hypotensive effect;
• drugs with uricosuric action - benzbromarone, probenecid (reduced uricosuric effect due to competitive suppression of renal tubular excretion of uric acid).

When used simultaneously with metamizole, a decrease in the effect of ASA on platelet aggregation is observed, therefore, in patients taking low doses of ASA for the purpose of cardioprotection, this combination should be used with caution.

When used simultaneously (within one day) with ibuprofen and naproxen, antagonism is observed in relation to irreversible platelet inhibition caused by the action of ASA. The clinical significance of this effect is unknown. The combination of ASA with ibuprofen is not recommended in patients at high risk of cardiovascular disease due to a possible decrease in the cardioprotective effects of ASA. When used simultaneously with systemic glucocorticosteroids (GCS) (with the exception of hydrocortisone or other GCS used for replacement therapy of Addison's disease), there is an increase in the elimination of salicylates and, accordingly, a weakening of their effect. When using GCS and salicylates in combination, it should be remembered that during treatment the level of salicylates in the blood is reduced, and after discontinuation of GCS, an overdose of salicylates is possible.

special instructions

Thrombo ACC® should be used with caution in the following conditions:

- Hypersensitivity to analgesics, anti-inflammatory drugs, antirheumatic drugs, as well as allergic reactions to other substances.

- A history of ulcerative lesions of the gastrointestinal tract, including chronic and recurrent lesions of the gastrointestinal tract or a history of gastrointestinal bleeding.

- Simultaneous use with anticoagulants (see section “Interaction with other drugs”).

- In case of impaired renal function or circulatory disorders resulting from atherosclerosis of the renal arteries, congestive heart failure, hypovolemia, major surgery, sepsis or cases of massive bleeding, since in all these cases ASA may increase the risk of developing acute renal failure and impaired renal function.

— In severe forms of glucose-b-phosphate dehydrogenase deficiency, ASA can cause hemolysis and hemolytic anemia. Factors that may increase the risk of hemolysis include fever, acute infections and high doses of the drug.

- In case of liver dysfunction.

— Some NSAIDs (ibuprofen, naproxen) can weaken the inhibitory effect of ASA on platelet aggregation. Patients taking ASA and planning to take NSAIDs should discuss this with their doctor (see section "Interactions with other drugs").

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

— The inhibitory effect of ASA on platelet aggregation persists for several days after administration, and therefore there may be an increased risk of bleeding during surgery or in the postoperative period (including minor surgical operations, such as tooth extraction).

- ASA in low doses reduces the excretion of uric acid, which can lead to attacks of gout in patients prone to this disease.

— Exceeding the dose of ASA is associated with the risk of gastrointestinal bleeding.

— Overdose is especially dangerous in elderly patients.

The drug should be used after a doctor's prescription.

Impact on the ability to drive vehicles and machinery

Taking the drug Trombo ACC® does not affect the ability to drive vehicles and machines.

Release form

Enteric film-coated tablets 50 mg and 100 mg.

14 tablets each or 20 tablets in a PVC/Al blister.

2 blisters (for 14 tablets) or 5 blisters (for 20 tablets) along with instructions for use in a cardboard box.

Storage conditions

Store in a place protected from light, at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Best before date

3 years.

Do not use after the expiration date stated on the packaging.

Vacation conditions

Over the counter.

Registration Certificate Holder

Bausch Health LLC, 115162, Moscow, st. Shabolovka, 31, building 5, Russia.

Manufacturer

Manufacturer of finished dosage form, prepacker, packer:

“G.L. Pharma GmbH, Industrialstrasse 1, 8502 Lannach, Austria.

Release quality control:

“G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria.

“G.L. Pharma GmbH, Industrialstrasse 1, 8502 Lannach, Austria.

Thrombo ASS®

When used simultaneously, ASA enhances the effect of the following drugs; If it is necessary to use ASA simultaneously with the listed drugs, the need to reduce the dose of these drugs should be considered:

- methotrexate, by reducing renal clearance and displacing it from protein binding;

- when used simultaneously with anticoagulants, thrombolytic and antiplatelet agents (ticlopidine, clopidogrel), there is an increase in the risk of bleeding as a result of the synergism of the main therapeutic effects of the drugs used;

- when used simultaneously with drugs that have anticoagulant, thrombolytic or antiplatelet effects, there is an increased damaging effect on the gastrointestinal mucosa;

- selective serotonin reuptake inhibitors, which may lead to an increased risk of bleeding from the upper gastrointestinal tract (synergism 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 the hypoglycemic properties of ASA itself in high doses and displacing sulfonylurea derivatives from binding with blood plasma proteins;

- when used simultaneously with valproic acid, its toxicity increases due to the displacement of its connection with 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 synergistic action); when used simultaneously with ibuprofen, antagonism is observed in relation to irreversible platelet inhibition caused by the action of ASA, which leads to a decrease in the cardioprotective effects of ASA;

— ethanol (increased risk of damage to the gastrointestinal mucosa and prolongation of bleeding time as a result of the mutual enhancement of the effects of ASA and ethanol).

Concomitant use of ASA in high doses may weaken the effect of the following drugs; If it is necessary to simultaneously prescribe ASA with the listed drugs, the need to adjust the dose of the listed drugs should be considered:

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

- angiotensin-converting enzyme (ACE) inhibitors (a dose-dependent decrease in GFR is noted as a result of inhibition of prostaglandins that have a vasodilatory effect, respectively, a weakening of the hypotensive effect. A clinical decrease in GFR is observed with a daily dose of ASA more than 160 mg. In addition, there is a decrease in the positive cardioprotective effect of ACE inhibitors, prescribed to patients for the treatment of chronic heart failure. This effect is also manifested when used in conjunction with ASA in large doses).

- drugs with uricosuric action - benzbromarone, probenecid (reduced 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 replacement therapy of Addison's disease), there is an increase in the excretion of salicylates and, accordingly, a weakening of their effect.