Instructions Aspirin Cardio 100 mg No. 98
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 patient groups.
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 salicylic acid breakdown; 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, gastroschisis).
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).
- Reducing the risk of developing coronary thrombosis after myocardial infarction (prevention of recurrent infarction).
- Prevention of myocardial infarction together with other therapeutic measures in patients at very high risk of developing cardiovascular events (according to the benefit-risk assessment 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 drugs or to any component of the drug.
- History of bronchospasm, urticaria or allergic symptoms after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
- Hemorrhagic diathesis.
- Active gastric and/or duodenal ulcer or gastrointestinal bleeding. Inflammatory diseases of the gastrointestinal tract (such as Crohn's disease, ulcerative colitis).
- Severe liver failure (cirrhosis and ascites).
- Severe renal failure (creatinine clearance < 30 ml/min).
- Severe heart failure (class III–IV according to the New York Cardiology Association functional classification of chronic 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”).
- Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
- Treatment of postoperative pain after coronary artery bypass grafting (using a heart-lung machine).
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: methotrexate toxicity increases (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.
- Enhancement of the effects and adverse reactions of all nonsteroidal anti-rheumatic drugs.
- Concomitant use with NSAIDs such as ibuprofen or naproxen on the same day may attenuate the irreversible inhibition of platelets by acetylsalicylic acid. The clinical significance of this interaction is unknown. Treatment of patients at risk of cardiovascular disease with NSAIDs such as ibuprofen or naproxen may limit the cardioprotective effect of acetylsalicylic acid (see section "Special warnings and precautions for use").
- Metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation when taken simultaneously. Therefore, metamizole should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
- Antihypertensive agents (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: reduced 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 half-life of penicillin from blood plasma.
Application features
Aspirin Cardio® is used with caution in the following situations:
- impaired renal function 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 impaired renal function and acute renal failure;
- liver dysfunction;
- simultaneous 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");
- symptoms of chronic gastric or duodenal dyspepsia or their recurrence;
- bronchial asthma or a general tendency to hypersensitivity, since acetylsalicylic acid may cause 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;
- 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;
- simultaneous use of anticoagulants;
- 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);
- 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.
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.
For some selective COX-2 inhibitors, placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications. It is currently unknown whether this risk is directly correlated with the COX-1/COX-2 selectivity of the respective NSAID. Since there are currently no comparable clinical trial data for acetylsalicylic acid at maximum doses and as long-term therapy, a similar increased risk cannot be excluded. Until such data are available, acetylsalicylic acid should only be used after a careful benefit/risk assessment in clinically proven ischemic heart disease, cerebrovascular disease, occlusive peripheral arterial disease or in patients with significant risk factors (such as hypertension, hyperlipidemia, diabetes mellitus, smoking). In such cases, the lowest effective dose should be used for the shortest possible duration of therapy.
The effect of NSAIDs on the kidneys is manifested, in particular, by fluid retention with edema and/or hypertension. Acetylsalicylic acid should be used with caution in patients with cardiac dysfunction and other conditions that contribute to fluid retention.
Caution is also necessary in patients receiving concomitant diuretics or ACE inhibitors and in those at increased risk of hypovolemia.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium-free’.
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.
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.
During the first and second trimesters of pregnancy
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 the drug is used in therapeutic doses. Prenatal monitoring for the detection of ductus arteriosus after taking acetylsalicylic acid should be considered, starting from the 20th week of pregnancy. In the event of ductus arteriosus, acetylsalicylic acid therapy should be discontinued.
During the third trimester of pregnancy
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 the 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 pregnant women and prolongation of labor.
Given this, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.
Fertility: The use of acetylsalicylic acid may impair female fertility and is therefore not recommended in women attempting to conceive. For women attempting to conceive or undergoing investigation of infertility, discontinuation of acetylsalicylic acid should be considered.
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).
Ability to influence reaction speed when driving vehicles or other mechanisms
Aspirin Cardio® does not affect the reaction speed when driving or using other mechanisms.
Method of administration and 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, since this dosage form of ASA has an enteric coating and absorption 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.
Therapy.
Due to life-threatening conditions resulting from severe intoxication, all necessary precautions should be taken immediately: immediate hospitalization, prevention or reduction of absorption 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, not known (cannot be determined from available data).
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.
Blood and lymphatic system disorders:
prolonged bleeding time;
rare: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia, iron deficiency anemia.
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.
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 (Lyell's syndrome).
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.
Formation of intestinal diaphragm-like structures, especially with prolonged use.
Hepatobiliary disorders:
rare: hepatic dysfunction;
very rare: increased transaminase levels.
From the kidneys and urinary tract:
rare: renal dysfunction;
not known: acute renal failure.
Others:
very rare: Reye's syndrome (see section "Special warnings and precautions for use").
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.
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, 4 or 7 blisters in a cardboard pack.
Vacation category
Without a prescription.
Producer
Primary, secondary packaging and batch release:
Bayer Bitterfeld GmbH, Germany
Bayer Bitterfeld GmbH, Germany
Location of the manufacturer and its business address
Ortsteil Gräppin, Seilgaster Schloss 1, 06803 Bitterfeld-Wolfen, Germany
Ortsteil Greppin, Salegaster Chaussee 1, 06803 Bitterfeld-Wolfen, Germany
