Aspecard

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ASPECARD

Composition:

Active ingredient: acetylsalicylic acid;

1 tablet contains 0.1 g (100 mg) of acetylsalicylic acid;

Excipients: microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silicon dioxide, stearic acid.

Medicinal form. Tablets.

Main physicochemical characteristics: white tablets with flat upper and lower surfaces and rounded edges.

Pharmacotherapeutic group. Antithrombotic agents.

ATC code B01AC06.

Pharmacological properties.

Pharmacodynamics.

Acetylsalicylic acid inhibits platelet aggregation by blocking the synthesis of thromboxane A2. Its mechanism of action involves irreversible inactivation of the enzyme cyclooxygenase (COX-1). This inhibitory effect is particularly pronounced in platelets, as they are unable to resynthesize the enzyme. Acetylsalicylic acid also exerts other inhibitory effects on platelets. Due to these effects, it is used in the management of various vascular diseases.

Acetylsalicylic acid belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and has analgesic, antipyretic, and anti-inflammatory properties. Orally administered in higher doses, acetylsalicylic acid is indicated for pain relief and mild febrile conditions such as colds and influenza, for reducing fever and alleviating joint and muscle pain, as well as in acute and chronic inflammatory disorders such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

Pharmacokinetics.

Salicylic acid and its metabolites are primarily excreted from the body via the kidneys.

In animal studies, salicylates at high doses caused kidney damage but did not lead to any other organ toxicity.

Acetylsalicylic acid has been extensively studied in vitro and in vivo for mutagenicity, but no evidence of mutagenic potential has been found. Similarly, studies on carcinogenicity have shown no concerning findings. However, salicylates have demonstrated teratogenic effects in studies conducted on various animal species.

Impairments in implantation, embryotoxic and fetotoxic effects, as well as learning disabilities in offspring, have been reported following drug administration during the prenatal period.

Clinical characteristics.

Indications.

For reduction of the risk of:

• death in patients with suspected acute myocardial infarction;
• morbidity and mortality in patients who have suffered myocardial infarction;
• transient ischemic attacks (TIA) and stroke in patients with TIA;
• morbidity and mortality in stable and unstable angina pectoris;
• myocardial infarction in patients at high risk of cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and in patients with multifactorial risk of cardiovascular diseases (hyperlipidemia, obesity, smoking, advanced age).

For prevention of:

• thrombosis and embolism following vascular surgery (percutaneous transluminal coronary angioplasty (PTCA), carotid endarterectomy, coronary artery bypass grafting (CABG), arteriovenous shunting);
• deep vein thrombosis and pulmonary artery embolism following prolonged immobilization (after surgical procedures).

For secondary prevention of stroke.

Contraindications.

• Hypersensitivity to acetylsalicylic acid, other salicylates, or any component of the medicinal product.
• Asthma induced by salicylates or substances with similar action, particularly NSAIDs, in medical history.
• Acute peptic ulcers.
• Hemorrhagic diathesis.
• Severe renal failure.
• Severe hepatic failure.
• Severe congestive heart failure.
• Combination with methotrexate at doses of 15 mg/week or higher – increases 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).
• Third trimester of pregnancy (see section "Use in pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

Contraindications for concomitant use.

• Concomitant use of acetylsalicylic acid and methotrexate at doses of 15 mg/week or higher increases 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) (see section "Contraindications").

Combinations requiring cautious use.

• When acetylsalicylic acid is used concomitantly with methotrexate at doses less than 15 mg/week, hematological toxicity of methotrexate may increase (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, sulfonylureas): possible reduction in blood glucose levels. Concomitant use of high doses of acetylsalicylic acid with sulfonylurea derivatives may enhance the hypoglycemic effect of the latter due to displacement of protein-bound sulfonylurea by acetylsalicylic acid.
• Concomitant use of acetylsalicylic acid with NSAIDs such as ibuprofen or naproxen interferes with irreversible platelet inhibition by acetylsalicylic acid. The clinical significance of this interaction is unknown. Treatment with ibuprofen or naproxen in patients at risk of cardiovascular diseases may limit the cardioprotective effect of acetylsalicylic acid (see section "Special precautions").
• Enhanced effect when acetylsalicylic acid is used concomitantly with anticoagulants, thrombolytics, other platelet aggregation inhibitors or hemostasis inhibitors, barbiturates, lithium, sulfonamides, and triiodothyronine – increased risk of bleeding.
• Concomitant use of high-dose salicylates with NSAIDs (due to mutually potentiating effects) increases the risk of development of ulcers and gastrointestinal bleeding.
• When used concomitantly with selective serotonin reuptake inhibitors (SSRIs), the risk of gastrointestinal bleeding increases due to synergistic effects.
• When used concomitantly with digoxin, plasma concentration of the latter increases due to reduced renal excretion.
• Diuretics in combination with high doses of acetylsalicylic acid: reduced efficacy of diuretics. Concomitant use with acetylsalicylic acid leads to reduced efficacy of aldosterone antagonists (e.g., spironolactone) and loop diuretics.
• Systemic glucocorticoids: increased risk of gastrointestinal ulcers and bleeding. Systemic glucocorticosteroids (except hydrocortisone used for replacement therapy in Addison's disease) reduce blood levels of salicylates and increase the risk of salicylate overdose after discontinuation of glucocorticosteroid therapy.
• Antihypertensive agents (ACE inhibitors and β-blockers): if patients are treated concomitantly with Aspecard and these medicinal products, careful monitoring of blood pressure is recommended, with dose adjustment if necessary. Angiotensin-converting enzyme (ACE) inhibitors in combination with high doses of acetylsalicylic acid cause reduced glomerular filtration due to inhibition of the vasodilatory effect of prostaglandins and reduced antihypertensive effect.
• When used concomitantly with valproic acid, acetylsalicylic acid displaces it from plasma protein binding, increasing its toxicity. As a result, valproate plasma levels increase, leading to a higher frequency of adverse reactions and symptoms of intoxication such as tremor, nystagmus, ataxia, and personality changes.
• Alcohol promotes damage to the gastrointestinal mucosa and prolongs bleeding time due to synergism between acetylsalicylic acid and alcohol.
• Concomitant use with uricosuric agents such as benzbromarone, probenecid, sulfinpyrazone, and sulfinprazon reduces uric acid excretion (due to competition for renal tubular excretion of uric acid).
• Prolongation of penicillin plasma half-life.

Special precautions for use.

Acetylsalicylic acid should be used with caution in the following cases:

• hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents, as well as in the presence of allergy to other substances;
• gastrointestinal ulcers, including chronic or recurrent ulcers or gastrointestinal bleeding in medical history;
• presence of symptoms of chronic gastric or duodenal dyspepsia or their recurrence;
• concomitant use of anticoagulants;
• renal function impairment or cardiovascular circulation disorders (such as renal vascular pathology, congestive heart failure, hypovolemia, major surgeries, sepsis, or severe bleeding), since acetylsalicylic acid may also increase the risk of renal function impairment and acute renal failure;
• severe glucose-6-phosphate dehydrogenase deficiency, as acetylsalicylic acid may cause hemolysis or hemolytic anemia, especially in the presence of risk factors for hemolysis such as high drug doses, fever, or infectious processes;
• hepatic function impairment.

Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. If Aspecard is used before starting ibuprofen as an analgesic, the patient should consult a physician.

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 polyps, or chronic respiratory disease, and allergic reactions (e.g., skin reactions, pruritus, urticaria) to other substances in medical history.

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 severity of bleeding during surgical procedures (including minor surgeries such as tooth extraction).

When low doses of acetylsalicylic acid are used, excretion of uric acid may be reduced. This may trigger gout attacks in predisposed patients.

Drugs containing acetylsalicylic acid should not be used in children and adolescents with acute viral respiratory infection (ARVI), with or without fever, without consulting a physician. In certain viral diseases, particularly influenza A, influenza B, and varicella, there is a risk of Reye's syndrome, a very rare but life-threatening condition requiring immediate medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant medication; however, a causal relationship has not been established. If these conditions are accompanied by persistent vomiting, this may be a manifestation of Reye's syndrome.

Use during pregnancy or breastfeeding.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate a risk of miscarriage and fetal malformations following the use of prostaglandin synthesis inhibitors early in pregnancy. The risk increases with higher doses and longer duration of therapy. According to available data, a link between acetylsalicylic acid use and increased risk of miscarriage has not been confirmed.

Epidemiological data on the occurrence of birth defects are inconsistent; however, an increased risk of gastroschisis cannot be excluded with acetylsalicylic acid use. Results from a prospective study on early pregnancy exposure (1st–4th month) involving approximately 14,800 mother-child pairs did not indicate an increased risk of malformations.

Animal studies have shown that the use of prostaglandin inhibitors leads to increased incidence of implantation disorders, post-implantation losses, and embryo/fetal death. Furthermore, a higher frequency of severe birth defects, including cardiovascular malformations, has been observed in animals treated with prostaglandin inhibitors during organogenesis. Salicylates have also been linked to adverse effects on the fetus (increased mortality, growth disturbances, salicylate intoxication). Animal studies with acetylsalicylic acid indicate reproductive toxicity.

During the first and second trimesters of pregnancy, drugs containing acetylsalicylic acid should not be prescribed unless clinically necessary. For women who may potentially be pregnant, or for women in the first and second trimesters of pregnancy, the dose of drugs containing acetylsalicylic acid should be as low as possible and the duration of treatment as short as possible.

Cases of implantation disorders, embryotoxic and fetotoxic effects, and effects on the child's learning ability due to prenatal exposure to salicylates have been reported.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus as follows:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• renal function impairment, potentially leading to renal failure with oligohydramnios.

At the end of pregnancy, prostaglandin synthesis inhibitors may affect the mother and child as follows:

• potential prolongation of bleeding time, anti-aggregatory effect, even after very low doses;
• inhibition of uterine contractions, which may lead to delayed or prolonged labor.

Due to these risks, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.

Salicylates are excreted into breast milk. Concentrations in breast milk are equivalent to or even higher than those in maternal plasma.

If use is necessary during lactation, breastfeeding should be discontinued in case of regular use of high doses (> 300 mg/day).

Ability to influence reaction speed when driving or operating machinery.

No effects on the ability to drive or operate machinery have been observed.

Dosage and Administration

The drug should be taken orally, 30–60 minutes before meals, without chewing, and with sufficient fluid.

To reduce the risk of death in patients with suspected acute myocardial infarction, administer the drug at a dose of 100–300 mg per day. A maintenance dose of 100–300 mg per day should be continued for 30 days after myocardial infarction.

After 30 days, consideration should be given to further prevention of recurrent myocardial infarction.

To achieve rapid absorption for this indication, the first tablet must be chewed.

To reduce the risk of disease and fatal outcomes in patients who have experienced myocardial infarction, administer 100–300 mg per day.

For secondary prevention of stroke, administer the drug at a dose of 100–300 mg per day.

To reduce the risk of transient ischemic attack (TIA) and stroke in patients with TIA, administer 100–300 mg per day.

To reduce the risk of disease development and fatal outcomes in patients with stable and unstable angina, administer 100–300 mg per day.

For prevention of thromboembolism after vascular procedures (percutaneous transluminal coronary angioplasty [PTCA], carotid endarterectomy, coronary artery bypass grafting [CABG], arteriovenous shunting), administer the drug at a dose of 100–200 mg daily or 300 mg every other day.

For prevention of deep vein thrombosis and pulmonary embolism after prolonged immobilization (following surgical procedures), administer 100–200 mg per day or 300 mg every other day.

For prevention of myocardial infarction in patients at high risk of cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and in patients with multiple risk factors for cardiovascular disease (hyperlipidemia, obesity, smoking, advanced age), administer 100 mg per day or 300 mg every other day.

Children.

The medicinal product Aspecard is not used in children.

Administration of acetylsalicylic acid to children under 16 years of age may cause severe adverse effects (including Reye's syndrome, one of the signs of which is persistent vomiting).

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 occur, and at doses > 300 mg/kg body weight, severe intoxication may occur.

Toxic effects of salicylates may occur as a result of chronic intoxication due to prolonged therapy (administration of more than 100 mg/kg/day for more than 2 days may cause toxic effects), or as a result of acute, life-threatening intoxication (overdose), which may be caused, for example, by accidental ingestion in children or unexpected overdose.

Chronic salicylate poisoning may have a hidden course, as its signs and symptoms are nonspecific. Moderate chronic intoxication caused by salicylates, or salicylism, usually occurs only after repeated intake of large doses.

Acute intoxication is characterized by pronounced disturbances in acid-base balance, which may vary depending on the patient's age and severity of intoxication. The most common manifestation in children is metabolic acidosis. The severity of the condition cannot be assessed solely based on plasma salicylate concentration. Absorption of acetylsalicylic acid may be delayed due to delayed gastric emptying or formation of concretions in the stomach.

Symptoms. Dizziness, vertigo, tinnitus, hearing loss, excessive sweating, nausea and vomiting, headache, hypocalcemia or hypoglycemia, skin rash, gastrointestinal bleeding, inhibition of thrombosis leading to coagulopathy, cardiovascular disorders (from arrhythmia and arterial hypotension to cardiac arrest), tinnitus, visual and hearing disturbances, tremor, confusion, hyperthermia, hyperventilation, disturbances in acid-base balance and electrolyte imbalance, dehydration, coma, and respiratory failure.

Tinnitus may occur at plasma salicylate concentrations above 150–300 µg/mL. More serious adverse reactions occur at plasma salicylate concentrations above 300 µg/mL.

Treatment. Treatment of acute intoxication caused by acetylsalicylic acid overdose is determined by the severity and clinical symptoms and involves standard measures used in poisoning cases. All measures taken should aim to accelerate drug elimination and restore electrolyte and acid-base balance.

Due to life-threatening conditions resulting from severe intoxication, all necessary preventive measures should be initiated immediately: prevention or reduction of resorption, gastric lavage in the early stages (within one hour after ingestion), activated charcoal, monitoring and appropriate correction of electrolytes. Administration of glucose. Administration of sodium bicarbonate to correct acidosis and to accelerate elimination (urine pH > 8). Administration of glycine: initial dose – 8 g orally, then 4 g every 2 hours for 16 hours. Hemoperfusion or hemodialysis may be required (the need for use may be determined at a toxicology center).

Manifestations and symptoms, and laboratory findings due to complex pathophysiological effects of salicylate poisoning, and necessary therapeutic measures:

Adverse Reactions.

Gastrointestinal disorders:

Common: microbleeding (70%);

Uncommon:
dyspepsia, nausea, vomiting, diarrhea, heartburn, anorexia;

Rare:
epigastric and abdominal pain; gastrointestinal inflammation, erosive-ulcerative gastrointestinal lesions, which in very rare cases may potentially lead to gastrointestinal hemorrhages and perforations, with corresponding laboratory findings and clinical manifestations, gastrointestinal bleeding.

Blood and lymphatic system disorders:

Due to the antiplatelet effect of acetylsalicylic acid, an increased risk of bleeding may occur. Bleeding events observed include perioperative hemorrhages, hematomas, genitourinary bleeding, epistaxis, gingival bleeding, hematemesis, melena.

Rare or very rare: serious bleeding such as gastrointestinal hemorrhage, cerebral hemorrhage (especially in patients with uncontrolled hypertension and/or concomitant use of anticoagulant agents), which may be life-threatening.

Hemorrhages may lead to acute and chronic post-hemorrhagic anemia, iron-deficiency anemia (due to so-called occult microbleeding), with corresponding laboratory findings and clinical symptoms such as asthenia, pallor of the skin, hypoperfusion.

Rare: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia.

In patients with severe forms of glucose-6-phosphate dehydrogenase deficiency, hemolysis and hemolytic anemia have been reported during treatment with acetylsalicylic acid.

Immune system disorders:

Uncommon: hypersensitivity reactions with corresponding laboratory and clinical manifestations, including asthmatic state;

Rare: mild to moderate skin reactions, as well as reactions affecting the respiratory, gastrointestinal, and cardiovascular systems, including symptoms such as rash, urticaria, edema, pruritus, rhinitis, nasal congestion, bronchospasm, angioneurotic edema, asthma attacks, hypotension progressing to shock, cardiopulmonary failure;

Very rare: severe skin reactions, including exudative polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic shock.

Metabolism and nutrition disorders:

Rare: hypoglycemia, iron-deficiency anemia, acid-base imbalance.

Nervous system disorders:

Rare: headache, dizziness, tinnitus, visual disturbances, hearing disturbances, confusion.

Hepatobiliary disorders:

Rare: hepatic dysfunction, transient hepatic insufficiency, elevated transaminase levels.

Renal and urinary disorders:
Reports of impaired renal function and development of acute renal failure have been received.

Reproductive system disorders:
menorrhagia.

Other:

Rare: Reye's syndrome (see section "Special precautions").

Additional adverse reactions have been reported spontaneously for all dosage forms of aspirin, including oral short-term and long-term therapy. Therefore, classification of frequency categories according to CIOMS III is not possible.

Shelf life. 3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets per blister, 12 or 10 blisters per carton.

Prescription status.

Over-the-counter (without prescription).

Manufacturer. UAB "MARIPHARM".

Manufacturer's address and location of operations.

Minarikova 8, Maribor, 2000, Slovenia.

Marketing Authorization Holder.

UAB "STYROLBIOFARM BALTICUM".

Address of Marketing Authorization Holder.

LV-1050, Riga, Latvia, Rasas Street 5.