Instructions Aspirin Cardio enteric-coated tablets 100 mg blister No. 28
Composition
active ingredient: acetylsalicylic acid;
1 tablet contains acetylsalicylic acid 100 mg;
excipients: powdered cellulose, corn starch, methyl acrylate copolymer (type A), sodium lauryl sulfate, polysorbates, talc, triethyl citrate.
Dosage form
Enteric-coated tablets.
Main physicochemical properties: white, film-coated tablets.
Pharmacotherapeutic group
Antithrombotic agents.
ATX code B01A C06.
Pharmacological properties
Pharmacodynamics
Mechanism of action. The antithrombotic effect of acetylsalicylic acid is due to the blockade of thromboxane A2 synthesis in platelets. Since even small doses of acetylsalicylic acid (ASA) are absorbed, all circulating platelets on the way from the gastrointestinal tract to the liver are irreversibly inhibited in the prehepatic mesenteric blood vessels. At the same time, ASA concentrations during the posthepatic circulation only slightly inhibit endothelial cyclooxygenase (responsible for the synthesis of prostacyclin), since it is restored more quickly. The function of platelets responsible for hemostasis is not significantly changed.
Clinical efficacy.
Primary prevention. A meta-analysis by the American Preventive Services Task Force (Ann Int Med 2002;136:161–172) based on 5 prospective clinical trials demonstrated that the risk of myocardial infarction (hazard ratio 0.72 (95% confidence interval: 0.60–0.87)) is reduced by prophylactic treatment with acetylsalicylic acid 75–125 mg for 5–7 years in patients without previous cardiovascular events but with various risk factors (age > 50 years, hypertension, diabetes mellitus, smoking, hypercholesterolemia, family history). This was demonstrated only for nonfatal cardiovascular events; no benefit was observed for stroke or all-cause mortality. The risk of developing severe gastrointestinal bleeding compared with controls was 0.8% versus 0.48%, and the risk of intracranial bleeding was 0.22% versus 0.17%. The risk of bleeding was higher in patients aged 70 years and older.
Prophylaxis should only be undertaken after satisfactory blood pressure control has been achieved and in combination with other therapeutic measures (diet, treatment of diabetes and lipid metabolism, smoking cessation). The risk can be assessed using the European Society of Cardiology scales (European Heart Journal, 1998,19:1434-1503).
Secondary prevention. In a meta-analysis conducted by the Antithrombotic Trialists Collaboration (BMJ 2002;324:71–85), the effects of acetylsalicylic acid and placebo were compared in 287 trials involving 135,000 high-risk patients, with an additional comparison of different platelet aggregation inhibitors involving 77,000 patients. High-risk patients were defined as patients with an acute cardiovascular event or a history of cardiovascular events (myocardial infarction, transient ischemic attack (TIA), unstable angina, arterial occlusive disease, after surgical intervention such as coronary artery bypass grafting, percutaneous transluminal catheter angioplasty, peripheral angioplasty, and patients with arteriovenous shunts who are on dialysis).
There was a reduction in the risk of major cardiovascular events (relative reduction of 25%; p < 0.0001) and cardiovascular mortality. The absolute benefit outweighed the risks of extracranial bleeding in all high-risk categories of patients.
Pharmacokinetics
Absorption. 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. Due to the enteric coating of the tablets, the release of the active substance does not occur in the stomach, but in the alkaline environment of the intestine, which in turn leads to a slowdown in the absorption of acetylsalicylic acid. Due to the presence of protection of the gastric mucosa, this dosage form is preferable compared to conventional forms of ASA, especially with long-term therapy. Compared with Aspirin, the maximum concentrations of salicylates in the blood plasma are reached 2–7 hours later.
Distribution: Salicylic acid is 60–90% bound to plasma proteins.
The bioavailability of salicylates is 80 to 100%.
Metabolism: The half-life of systemically available ASA is approximately 15 minutes. Salicylic acid, formed during hydrolysis, has a half-life of approximately 2–3 hours, which increases significantly after high doses (> 3 g) due to saturation of the binding enzyme system.
Excretion: Excretion is almost entirely renal in the form of salicylic acid (about 10%), salicylouric acid (about 75%), and salicylouric acid conjugates (about 10%). The half-life ranges from 2–3 hours after low doses to 12 hours after analgesic doses.
Kinetics in special clinical situations.
Elimination in patients with hepatic insufficiency: Since ASA is metabolized primarily in the liver, slow degradation of ASA to salicylic acid (cumulation) is expected.
Elimination in patients with renal insufficiency. Renal insufficiency does not affect the rate of degradation of salicylic acid; in contrast, the concentration of inactive metabolites of salicylic acid, mainly conjugated salicyluric acid, is increased.
Salicylates cross the placenta, but are found in breast milk only in small amounts.
Preclinical data
The preclinical safety profile of acetylsalicylic acid is well documented. In animal studies, salicylates caused kidney damage without any other organic lesions. Acetylsalicylic acid has been adequately investigated for mutagenicity and carcinogenicity; no relevant evidence of mutagenic or carcinogenic properties was found. Salicylates have been shown to be embryotoxic and teratogenic in studies in various animal species (e.g. cardiac and skeletal malformations, gastoschisis).
Cases of implantation disorders, embryotoxic and fetotoxic effects and effects on the child's learning ability have been reported after prenatal exposure to salicylates.
Indication
prevention of thrombosis (reocclusion prevention) after coronary artery bypass grafting, percutaneous transluminal catheter angioplasty and after arteriovenous bypass grafting in patients on dialysis; prevention of cerebrovascular stroke after the appearance of warning signs (transient ischemic attack); reduction of the risk of coronary thrombosis after myocardial infarction (re-infarction prevention); prevention of myocardial infarction together with other therapeutic measures in patients with a very high risk of developing cardiovascular events (according to the assessment of the benefit and risk by the treating physician); unstable angina; prevention of arterial thrombosis after vascular surgery; as part of standard therapy for acute myocardial infarction; prevention of vascular occlusion in arterial occlusive disease.
Contraindication
Hypersensitivity to salicylates and/or other anti-inflammatory agents or to any component of the drug; history of asthma induced by the use of salicylates or substances with a similar effect, especially NSAIDs; hemorrhagic diathesis; acute peptic ulcers; severe hepatic insufficiency; severe renal insufficiency; severe congestive heart 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 (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
Contraindicated combinations
When used with methotrexate at doses of 15 mg/week or more, 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) (see section "Contraindications").
Combinations to be used with caution
When used with methotrexate at doses less than 15 mg/week: increased hematological toxicity of methotrexate (due to reduced renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
Antidiabetic agents (e.g. insulin, sulfonylurea): possible decrease in blood sugar levels.
Enhancement of the effects of anticoagulants/thrombolytics, barbiturates, lithium, sulfonamides and triiodothyronine.
Pharmacodynamic interactions may develop between selective serotonin reuptake inhibitors and acetylsalicylic acid: increased risk of bleeding due to synergistic effects.
Increased plasma concentrations of digoxin due to decreased renal excretion.
Increased plasma levels of phenytoin and valproate. When used simultaneously with valproic acid, ASA displaces it from its plasma protein binding, reducing its metabolism. 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.
Enhancement of the effects and adverse reactions of all nonsteroidal anti-rheumatic drugs.
Antihypertensives (ACE inhibitors and β-blockers): patients who simultaneously use Aspirin Cardio® and these drugs are recommended to carefully monitor blood pressure and adjust the dose if necessary.
Diuretics in combination with high doses of ASA: decreased diuretic effect.
Decreased effect of uricosuric agents (e.g. probenecid, sulfinpyrazone).
Systemic glucocorticosteroids: increased risk of gastrointestinal ulcers and bleeding. Decreased blood salicylate levels during corticosteroid therapy, risk of salicylate overdose after discontinuation of glucocorticosteroid therapy.
Alcohol: increased risk of gastrointestinal ulcers and bleeding, prolongation of bleeding time.
Prolongation of the plasma half-life of penicillin.
Application features
Aspirin Cardio is 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), since acetylsalicylic acid may also increase the risk of renal impairment and acute renal failure; impaired liver function; concomitant use of NSAIDs such as ibuprofen or naproxen, since NSAIDs may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. In the case of using Aspirin Cardio, the patient should consult a doctor before starting to take NSAIDs 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 haemolysis or haemolytic anaemia. Factors that may increase the risk of haemolysis include high doses of the drug, fever or acute infection; concomitant use of anticoagulants; due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after administration, the use of products containing acetylsalicylic acid may increase the likelihood or worsen existing bleeding during surgery (including minor surgery, e.g. tooth extraction).
When used in low doses, ASA reduces the excretion of uric acid. In patients who normally have a reduced level of uric acid excretion, this can lead to the development of gout.
The use of acetylsalicylic acid in children and adolescents with fever and/or viral diseases is possible only on the prescription of a doctor 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, and liver dysfunction).
Some viral diseases, especially influenza A, influenza B and chickenpox, carry a risk of developing Reye's syndrome, a very rare but life-threatening illness requiring immediate medical attention. The risk may be increased if acetylsalicylic acid is used as a concomitant medication, but a causal relationship has not been proven in this case. 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 analgesics, anti-inflammatory, antirheumatic drugs, as well as allergies to other substances.
Ability to influence reaction speed when driving vehicles or other mechanisms
Aspirin Cardio has not demonstrated the ability to affect the reaction rate when driving vehicles or other mechanisms.
Use during pregnancy or breastfeeding
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.
During the first and second trimesters of pregnancy, acetylsalicylic acid-containing drugs should not be prescribed unless clearly necessary. For women who may become pregnant and for pregnant women in the first and second trimesters, the dose of acetylsalicylic acid-containing drugs should be as low as possible and the duration of treatment should be as short as possible.
Animal studies have shown that the use of prostaglandin inhibitors leads to an increase in pre- and post-implantation losses and embryo/fetal death. In addition, an increased incidence of severe malformations, including cardiovascular malformations, has been observed in animals treated with prostaglandin inhibitors during organogenesis.
According to previous experience, the risk is low when using the drug in therapeutic doses.
All prostaglandin synthesis inhibitors can:
affect the fetus in the following ways: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); impaired renal function with possible further development of renal failure with oligohydramnios; affect the woman and fetus in the following ways: prolongation of bleeding time, antiaggregatory effect, which may occur even when using very low doses; inhibition of uterine contractions and bleeding in the pregnant woman and prolongation of labor.
Given this, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.
Breastfeeding. Salicylates are excreted in breast milk. Concentrations in breast milk are equivalent to or even higher than those in maternal plasma.
During forced use during lactation, breastfeeding should be discontinued in case of regular use of high doses (> 300 mg/day).
Method of administration and doses
Unless your doctor has prescribed a different dosage, it is recommended to use the following doses.
Cardiovascular indications without coronary artery bypass grafting and percutaneous transluminal catheter angioplasty: 1 × 100 mg/day.
Prevention of thrombosis after coronary artery bypass grafting and percutaneous transluminal catheter angioplasty: 100 - 300 mg/day.
Prevention of cerebrovascular stroke after the appearance of precursory manifestations (TIA): 3 × 100 mg/day or 1 × 300 mg/day.
It is recommended to take the tablet with a small amount of liquid at least 30 minutes before a meal. Wash down with ½–1 glass of water. In order to avoid the release of the active substance before reaching the alkaline environment of the intestine, the tablets should not be crushed, broken or chewed.
Acute myocardial infarction: in case of acute myocardial infarction, 200–300 mg of acetylsalicylic acid should be administered intravenously or orally in a rapid-release form of acetylsalicylic acid (not enteric-coated). Enteric-coated tablets of acetylsalicylic acid should be crushed or chewed before administration to achieve faster absorption. Thereafter, 100 mg of Aspirin Cardio should be administered daily.
Children
Aspirin Cardio is not used in children and adolescents (under 18 years of age) due to the lack of data on the effectiveness and safety of use in this category of patients.
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
Severe intoxication can be life-threatening. Newborns are more sensitive than adults. Symptoms of severe poisoning can develop acutely or slowly, for example, within 12–24 hours after administration. After oral administration of ASA doses up to 150 mg/kg body weight, moderate intoxication may develop, and at doses > 300 mg/kg body weight, severe intoxication may develop.
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.
The severity of the condition cannot be assessed solely on the basis of plasma salicylate concentrations. Arterial blood gas (ABG) analysis should be closely monitored, as therapy is based not on blood salicylate levels but on clinical symptoms and ABG.
Reservation.
Local signs of irritation that usually dominate in ASA overdose, such as nausea, vomiting, and stomach pain, may be absent because this dosage form of ASA has an enteric coating and resorption occurs only in the small intestine.
Symptoms.
Headache, nausea, hypoglycemia or hyperglycemia, skin rash, dizziness, tinnitus, visual and hearing impairment, tremor, confusion, hyperthermia, increased sweating, hyperventilation, respiratory alkalosis with metabolic compensation leading to metabolic acidosis, electrolyte imbalance, dehydration, convulsions, coma, respiratory failure syndrome, cardiac arrhythmia.
Symptoms of chronic salicylate poisoning are nonspecific (e.g. tinnitus, headache, irritability, excessive sweating, hyperventilation) and therefore may go unnoticed.
Due to life-threatening conditions resulting from severe intoxication, all necessary precautions should be taken immediately: immediate hospitalization, prevention or reduction of resorption by taking appropriate doses of activated charcoal within the first 4 hours (10 times the amount of activated charcoal relative to the weight of ASA); in case of severe intoxication, gastric lavage or gastroscopic removal of tablets.
Appropriate electrolyte monitoring and correction. Use of glucose, sodium bicarbonate in the early stages to correct acidosis and to accelerate excretion (urine pH > 8), improve diuresis, cooling in the setting of hyperthermia, benzodiazepine for seizures.
Hemodialysis is possible in case of severe intoxication.
Cases of decompensation resulting in death after intubation have been described. Therefore, if possible, intubation should be performed after the start of alkalinization, the time of apnea should be minimized, and hyperventilation should be monitored for maintenance.
Detailed information can be obtained from the poison control center.
Adverse reactions
Within each group, adverse reactions are presented in order of decreasing seriousness: very common: ≥ 1/10; common: ≥ 1/100 - < 1/10; uncommon: ≥ 1/1000 - < 1/100; rare: ≥ 1/10000 - < 1/1000; very rare: < 1/10000.
Other adverse reactions have been reported spontaneously for all formulations of acetylsalicylic acid, including oral short-term and long-term therapy, and therefore no frequency categories can be assigned.
Hemolysis and hemolytic anemia have been observed in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Due to its antiaggregatory effect, the use of ASA 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.
Blood and lymphatic system disorders:
prolonged bleeding time;
rare: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia, iron deficiency anemia.
On the part of the immune system:
uncommon: 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 rare: severe skin reactions, including exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Metabolism and nutrition:
very rare: hypoglycemia, acid-base imbalance.
From the nervous system:
rare: headache, dizziness, tinnitus, visual impairment, hearing impairment, confusion.
From the gastrointestinal tract:
very common: microbleeds (70%);
common: gastric symptoms;
uncommon: dyspepsia, nausea, vomiting, diarrhea;
rare: gastrointestinal bleeding, gastrointestinal ulcers, which in very rare cases may lead to perforation.
Hepatobiliary disorders:
rare: hepatic dysfunction;
very rare: increased transaminase levels.
From the kidneys and urinary tract:
rare: renal dysfunction;
Acute renal failure has been reported.
Other: very rare: Reye's syndrome (see section "Special warnings and precautions for use").
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
5 years.
Storage conditions
Store out of the reach of children at a temperature not exceeding 25 °C.
Packaging
14 tablets in a blister, 2 blisters in a cardboard pack.
Vacation category
Without a prescription.
Producer
Bayer Bitterfeld GmbH.
Location of the manufacturer and its business address
Ortsteil Gräppin, Seilgaster Schloss 1, 06803 Bitterfeld-Wolfen, Germany.
