Instructions for Acecor Cardio enteric-coated tablets 100 mg No. 100
Composition
active ingredient: acetylsalicylic acid;
1 tablet contains acetylsalicylic acid 100 mg;
Excipients: potato starch; talc; microcrystalline cellulose; citric acid, monohydrate; triethyl citrate; methacrylate copolymer (type A).
Dosage form
Enteric-coated tablets.
Main physicochemical properties: white tablets with a biconvex smooth surface, film-coated.
Pharmacotherapeutic group
Antithrombotic agents. Platelet aggregation inhibitors, except heparin. Acetylsalicylic acid. ATC code B01A C06.
Pharmacological properties
Pharmacodynamics.
Acetylsalicylic acid inhibits platelet aggregation by blocking the synthesis of thromboxane A2. Its mechanism of action is the irreversible inactivation of the enzyme cyclooxygenase (COX-1). This inhibitory effect is particularly pronounced for platelets, since they are unable to resynthesize this enzyme. It is also recognized that acetylsalicylic acid has other inhibitory effects on platelets, which makes it useful in many vascular diseases.
Acetylsalicylic acid belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesic, antipyretic and anti-inflammatory properties. Orally, in higher doses, acetylsalicylic acid can be used to relieve pain and mild feverish conditions such as colds and flu, to reduce fever and relieve joint and muscle pain, and in acute and chronic inflammatory diseases such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
Pharmacokinetics.
After oral administration, acetylsalicylic acid is rapidly and completely absorbed from the gastrointestinal tract. During and after absorption, it is converted into the main active metabolite - salicylic acid. The maximum concentration of acetylsalicylic acid in the blood plasma is reached after 10–20 minutes, salicylic acid - after 20–120 minutes. Due to the enteric coating of ACECOR CARDIO 100 mg tablets, the release of the active substance does not occur in the stomach, but in the alkaline environment of the intestine. Therefore, the absorption of acetylsalicylic acid is slowed down to 3–6 hours after taking a tablet coated with an enteric coating, compared to a regular acetylsalicylic acid tablet.
Acetylsalicylic and salicylic acids are completely bound to blood plasma proteins and are rapidly distributed in the body. Salicylic acid crosses the placenta and also enters breast milk.
Salicylic acid is metabolized primarily in the liver. The metabolites of salicylic acid are salicylicuric acid, phenolic and acyl glucuronides of salicylic acid, gentisic acid and gentisinuric acid.
The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by liver enzyme activity. The half-life is dose-dependent and increases from 2–3 hours at low doses to 15 hours at high doses. Salicylic acid and its metabolites are excreted mainly by the kidneys.
Preclinical data.
The preclinical safety profile of acetylsalicylic acid is well documented.
In animal studies, salicylates at high doses caused kidney damage and did not cause any other organic lesions.
Acetylsalicylic acid has been extensively studied in vitro and in vivo for mutagenicity, but no evidence of mutagenic potential has been found. The same applies to carcinogenicity studies.
Salicylates have been shown to be teratogenic in studies in various animal species. Implantation disorders, embryotoxic and fetotoxic effects, and learning disorders have been described in the offspring after prenatal use of the drug.
Indication
To reduce risk:
death in patients with suspected acute myocardial infarction;
morbidity and mortality in patients who have had myocardial infarction;
transient ischemic attacks (TIA) and stroke in patients with TIA;
morbidity and mortality in stable and unstable angina;
myocardial infarction in patients with a high risk of developing cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and individuals with a multifactorial risk of cardiovascular disease (hyperlipidemia, obesity, smoking, old age).
For prevention:
thrombosis and embolism after vascular surgery (percutaneous transluminal catheter angioplasty (PTCA), carotid endarterectomy, coronary artery bypass grafting (CABG), arteriovenous bypass grafting);
deep vein thrombosis and pulmonary embolism after long-term immobilization (after surgery).
For secondary prevention of stroke.
Contraindication
Hypersensitivity to acetylsalicylic acid, other salicylates or to any component of the drug;
history of asthma caused by the use of salicylates or substances with a similar effect, especially NSAIDs;
hemorrhagic diathesis;
acute peptic ulcers;
severe liver failure;
severe renal failure;
combination with methotrexate at a dosage of 15 mg/week or more (see section “Interaction with other medicinal products and other types of interactions”);
the last trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
Contraindications for simultaneous use.
The use of acetylsalicylic acid and methotrexate in doses of 15 mg/week or more increases the hematological toxicity of methotrexate (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
Combinations that should be used with caution.
When used with methotrexate at doses less than 15 mg/week, the hematological toxicity of methotrexate increases (due to a decrease in the renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates);
increased effects of anticoagulants, oral antidiabetic agents, barbiturates, lithium, sulfonamides and triiodothyronine;
increase in plasma levels of phenytoin and valproate. When used simultaneously with valproic acid, acetylsalicylic acid displaces it from its connection with plasma proteins, reducing the metabolism of the latter. As a result, plasma levels of valproate increase, which leads to an increase in the frequency of adverse reactions to signs of intoxication, such as tremor, nystagmus, ataxia and personality changes;
increased action and adverse reactions of all nonsteroidal anti-rheumatic drugs;
Concomitant use with ibuprofen prevents irreversible inhibition of platelets by acetylsalicylic acid. Treatment with ibuprofen in patients at risk of cardiovascular disease may limit the cardioprotective effect of acetylsalicylic acid (see section "Special warnings and precautions for use");
Pharmacodynamic interactions may occur between selective serotonin reuptake inhibitors and acetylsalicylic acid. Concomitant use of paroxetine with acetylsalicylic acid may increase the risk of gastrointestinal bleeding;
increased plasma concentration of digoxin due to decreased renal excretion;
reduced effect of aldosterone antagonists (e.g. spironolactone), loop diuretics, uricosuric agents (e.g. probenecid, sulfinpyrazone), antihypertensive agents (ACE inhibitors and β-blockers). Patients who simultaneously use ACECOR CARDIO and these drugs are recommended to carefully monitor blood pressure and adjust the dose if necessary;
prolongation of the half-life of penicillin from blood plasma;
Systemic glucocorticosteroids (excluding hydrocortisone, which is used for replacement therapy in Addison's disease) increase the risk of gastrointestinal bleeding and reduce the level of salicylates in the blood;
alcohol: increased risk of gastrointestinal bleeding and prolongation of bleeding time due to synergism of acetylsalicylic acid and alcohol;
reduction of the effect of uricosuric agents. Acetylsalicylic acid reduces the excretion of uric acid even when used in low doses. This can provoke the development of gout in patients with reduced excretion of uric acid;
Metamizole may inhibit the effect of acetylsalicylic acid on platelet aggregation when used concomitantly with acetylsalicylic acid, therefore this combination should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
Application features
ACEKOR CARDIO should be used with caution in the following situations:
renal impairment or cardiovascular circulatory disorders (e.g. renal vascular pathology, congestive heart failure, hypovolemia, extensive surgery, sepsis or severe bleeding), as acetylsalicylic acid may also increase the risk of renal impairment and acute renal failure;
liver dysfunction;
simultaneous use of ibuprofen, since ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. In the case of using ACECOR CARDIO, the patient should consult a doctor before starting to take ibuprofen as an analgesic (see section "Interaction with other medicinal products and other types of interactions");
the presence of symptoms of chronic gastric or duodenal dyspepsia or their recurrence;
the presence of bronchial asthma or a general tendency to hypersensitivity, since acetylsalicylic acid may cause the development of bronchospasm or an attack of bronchial asthma or other hypersensitivity reactions. Risk factors include a history of asthma, hay fever, nasal polyposis or chronic respiratory disease, a history of allergic reactions (e.g. rash, itching or urticaria) to other substances;
nasal polyps;
severe glucose-6-phosphate dehydrogenase deficiency, as acetylsalicylic acid may cause hemolysis or hemolytic anemia. Factors that may increase the risk of hemolysis include high doses of the drug, fever, or acute infectious process;
Due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after administration, the use of drugs containing acetylsalicylic acid may increase the likelihood or aggravate existing bleeding during surgical operations (including minor surgical interventions, such as tooth extraction);
The use of acetylsalicylic acid in children and adolescents with fever and/or viral diseases is possible only on prescription as a second-line therapy (due to the risk of developing Reye's syndrome, a life-threatening encephalopathy, the main symptoms of which are severe vomiting, loss of consciousness, liver dysfunction). With some viral diseases, especially influenza A, influenza B and chickenpox, there is a risk of developing Reye's syndrome, which is a very rare but life-threatening disease that requires urgent medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant medication, but a causal relationship in this case has not been proven. If these conditions are accompanied by persistent vomiting, this may be a manifestation of Reye's syndrome;
gastrointestinal ulcers, including chronic and recurrent peptic ulcers or a history of gastrointestinal bleeding;
hypersensitivity to analgesic, anti-inflammatory, antirheumatic drugs, as well as allergies to other substances.
Use during pregnancy or breastfeeding
Salicylates should be used with caution during the first and second trimesters of pregnancy. Salicylates are contraindicated during the third trimester of pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Available epidemiological data indicate an increased risk of miscarriage and cardiac malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy.
Available epidemiological data do not support an association between the use of acetylsalicylic acid and an increased risk of miscarriage. The available epidemiological data on miscarriage are not consistent, but an increased risk of gastroschisis cannot be excluded with the use of acetylsalicylic acid. The results of a prospective study of the effects of the drug in early pregnancy (1-4 months) involving approximately 14,800 woman-child pairs do not indicate any association with an increased risk of malformations.
In the first and second trimesters of pregnancy, preparations containing acetylsalicylic acid should not be prescribed unless clearly necessary. For women who may be pregnant or in the first and second trimesters of pregnancy, the dose of preparations containing acetylsalicylic acid should be as low as possible and the duration of treatment should be as short as possible.
Cases of implantation disorders, embryotoxic and fetotoxic effects, and effects on the child's learning ability have been reported following prenatal exposure to salicylates.
According to animal studies, the use of salicylates causes adverse reactions in the fetus (such as increased mortality, growth disorders, salicylate intoxication), but controlled studies involving pregnant women have not been conducted.
According to previous experience, the risk is low when using the drug in therapeutic doses.
In the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and/or renal dysfunction with possible further development of renal failure with oligohydramnios;
prolonged bleeding time, anti-aggregation effect that may occur in the woman and fetus at the end of pregnancy;
prolongation of bleeding time is also possible when using very low doses;
inhibition of uterine contractions and bleeding in pregnant women and prolongation of labor.
Given this, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.
Salicylates pass into breast milk. Concentrations in breast milk are equivalent to or even higher than those in maternal plasma.
During forced use according to indications during lactation, breastfeeding should be discontinued in case of regular use of high doses (> 300 mg/day).
Ability to influence reaction speed when driving vehicles or other mechanisms
No research was conducted.
Method of administration and doses
The drug should be taken orally 30–60 minutes before meals, without chewing, with sufficient liquid.
To reduce the risk of death in patients with suspected acute myocardial infarction, use the drug at a dose of 100-300 mg per day. Continue taking a maintenance dose of 100-300 mg per day for 30 days after the infarction. After 30 days, further prevention of recurrent myocardial infarction should be considered.
To achieve rapid absorption when used for this indication, the first tablet should be chewed.
To reduce the risk of morbidity and mortality in patients who have had a myocardial infarction, use 100–300 mg of the drug per day.
To reduce the risk of TIA and stroke in patients with TIA, use 100–300 mg per day.
To reduce the risk of disease progression and death in patients with stable and unstable angina: 100–300 mg per day.
For the prevention of thromboembolism after vascular surgery (PTCA, carotid endarterectomy, CABG, arteriovenous bypass surgery), use the drug at a dose of 100–200 mg per day every day or 300 mg per day every other day.
For the prevention of deep vein thrombosis and pulmonary embolism after long-term immobilization (after surgery) - 100-200 mg per day or 300 mg per day every other day.
To reduce the risk of myocardial infarction in patients with a high risk of developing cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and individuals with a multifactorial risk of cardiovascular disease (hyperlipidemia, obesity, smoking, old age, etc.), use 100 mg per day or 300 mg per day every other day.
Children.
According to the indications (see the "Indications" section), the drug ACEKOR CARDIO should not be used in children.
The use of acetylsalicylic acid in children under 16 years of age may cause serious side effects (including Reye's syndrome, one of the signs of which is persistent vomiting). Please read the information provided in the "Special instructions" section.
Overdose
Symptoms of severe poisoning may develop slowly, for example within 12–24 hours after administration. After oral administration of acetylsalicylic acid at doses up to 150 mg/kg body weight, moderate intoxication may develop, and at doses > 300 mg/kg body weight, severe intoxication may develop.
Chronic salicylate poisoning can be latent because its symptoms are nonspecific. Moderate chronic intoxication usually occurs only after repeated ingestion of large doses.
Acute intoxication is indicated by a pronounced change in acid-base balance, which may vary depending on the age of the patient and the severity of intoxication. Its most common manifestation in children is metabolic acidosis. The severity of the condition cannot be assessed solely on the basis of the concentration of salicylates in the blood plasma. The absorption of acetylsalicylic acid may be slowed down due to delayed gastric release, the formation of concrements in the stomach or when the drug is taken in the form of enteric-coated tablets.
Reservation.
Local signs of irritation that usually dominate in overdose of acetylsalicylic acid, such as nausea, vomiting and stomach pain, may be absent, since this dosage form of acetylsalicylic acid has an enteric coating and resorption occurs only in the small intestine.
Symptoms.
Headache, nausea, hypocalcemia or hypoglycemia, skin rash, dizziness, gastrointestinal bleeding, inhibition of thromboembolism to coagulopathy, cardiovascular disorders (from arrhythmia, arterial hypotension to cardiac arrest), rhinitis, visual and hearing impairment, tremor, confusion, hyperthermia, increased sweating, hyperventilation, acid-base and electrolyte imbalance, dehydration, coma and respiratory failure.
Tinnitus is possible at plasma salicylate concentrations above 150–300 μg/mL. More serious adverse reactions are observed at plasma salicylate concentrations above 300 μg/mL.
Therapy.
Due to life-threatening conditions due to severe intoxication, all necessary precautions should be taken immediately: prevention or reduction of resorption, gastric lavage in the early stages (up to 1 hour after ingestion), activated charcoal, monitoring and appropriate correction of electrolytes. Use of glucose. Sodium bicarbonate to correct acidosis and to accelerate excretion (urine pH > 8). Glycine: initial dose - 8 g orally, then - 4 g every 2 hours for 16 hours. Hemoperfusion or hemodialysis is possible (the need for use can be established in the poison control center).
Side effects
From the blood and lymphatic system: prolonged bleeding time; rarely - thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia.
Immune system disorders: infrequently - asthma; rare - hypersensitivity reactions such as erythematous/eczematous skin reactions, urticaria, rhinitis, nasal congestion, bronchospasm, angioedema, drop in blood pressure to the point of shock; very rarely - severe skin reactions, including exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Metabolism and metabolism: rarely - hypoglycemia, iron deficiency anemia, acid-base imbalance.
From the nervous system: rare - headache, dizziness, rhinitis, visual impairment, hearing impairment, confusion.
Gastrointestinal: often - microbleeds (70%), gastric symptoms; infrequently - dyspepsia, nausea, vomiting, diarrhea; rare - gastrointestinal bleeding, gastrointestinal ulcers, which very rarely can lead to perforation with corresponding clinical symptoms and changes in laboratory parameters.
Renal and urinary disorders: Renal dysfunction and acute renal failure have been reported.
Others: rarely - Reye's syndrome (see section "Special warnings and precautions for use").
Other adverse reactions have been reported spontaneously for all formulations of acetylsalicylic acid, including oral short-term and long-term therapy, and therefore a frequency category according to CIOMS III is not possible.
Hemolysis and hemolytic anemia have been observed in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Due to its antiplatelet effect, the use of acetylsalicylic acid may increase the risk of bleeding. Bleeding events such as perioperative bleeding, hematomas, epistaxis, urogenital bleeding, and gingival bleeding have been observed.
Serious bleeding events, such as gastrointestinal bleeding and haemorrhagic stroke, have been observed rarely or very rarely, particularly in patients with uncontrolled hypertension and/or concomitant use of anticoagulants, which in some cases can be potentially life-threatening.
Hemorrhages can lead to acute and chronic posthemorrhagic anemia/iron deficiency anemia (due to so-called occult microbleeding) with corresponding laboratory manifestations and clinical symptoms, such as asthenia, pallor of the skin, hypoperfusion.
Gastrointestinal disorders, such as general signs and symptoms of dyspepsia, epigastric pain and abdominal pain; in isolated cases - gastrointestinal inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which can potentially cause gastrointestinal hemorrhage and perforation in isolated cases with corresponding laboratory parameters and clinical manifestations.
Hypersensitivity reactions with associated laboratory and clinical manifestations include asthmatic status, mild to moderate skin reactions, as well as respiratory, gastrointestinal and cardiovascular reactions, including symptoms such as rash, oedema, pruritus, cardiorespiratory failure and very rarely severe reactions including anaphylactic shock.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store at a temperature not exceeding 30 °C in the original packaging.
Keep out of reach of children.
Packaging
50 or 100 tablets in a polymer jar in a cardboard pack.
50 tablets (10×5) or 100 tablets (25×4) in blisters in a cardboard pack.
Vacation category
Without a prescription.
Producer
LLC NVF "MICROCHEM".
(responsible for production and batch control/testing, including batch release)
Location of the manufacturer and address of its place of business.
Ukraine, 93000, Luhansk region, Rubizhne, Lenina st., building 33 (LLC NVF "MICROKHIM").
Ukraine, 01013, Kyiv, Budindustrii St., 5 (LLC NFE "MICROCHEM").
