Aspicard cardio

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AspiCard cardio

Composition:

Active ingredient: acetylsalicylic acid;

One tablet contains 100 mg or 300 mg of acetylsalicylic acid;

Excipients: microcrystalline cellulose, maize starch, crospovidone;

coating – Kollicoat MAE, propylene glycol, titanium dioxide (E 171), talc.

Pharmaceutical form. Enteric-coated tablets.

Main physicochemical properties: white or almost white, round, biconvex, film-coated tablets.

Pharmacotherapeutic group.

Antithrombotic agents. ATC code B01AC06.

Pharmacological properties.

Pharmacodynamics.

Acetylsalicylic acid (ASA) 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 this enzyme. It is also noted that acetylsalicylic acid 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 used to relieve pain and mild febrile conditions such as colds and flu, to reduce fever, and to alleviate joint and muscle pain in acute and chronic inflammatory conditions, including 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 its main active metabolite – salicylic acid. Maximum plasma concentration of acetylsalicylic acid is reached within 10–20 minutes, and of salicylic acid within 20–120 minutes. Due to the enteric coating of the tablets, the release of the active substance occurs not in the stomach, but in the alkaline environment of the intestine. Therefore, absorption of acetylsalicylic acid is delayed, taking 3–6 hours after administration of the enteric-coated tablet, compared to conventional acetylsalicylic acid tablets.

Acetylsalicylic acid and salicylic acid are completely bound to plasma proteins and rapidly distributed throughout the body. Salicylic acid crosses the placenta and is also excreted into breast milk.

Salicylic acid is metabolized primarily in the liver. Metabolites of salicylic acid include salicyluric acid, salicyl phenol glucuronide, salicyl acyl glucuronide, gentisic acid, and gentisic acid sulfate.

The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by hepatic enzyme capacity. The elimination half-life depends on the dose and increases from 2–3 hours with low doses to up to 15 hours with high doses. Salicylic acid and its metabolites are primarily excreted by the kidneys.

Preclinical data

The preclinical safety profile of acetylsalicylic acid is well documented.

In animal studies, high doses of salicylates caused kidney damage without any other organ involvement.

Acetylsalicylic acid has been extensively studied for mutagenicity, but no evidence of mutagenic potential has been found. The same applies to carcinogenicity studies. It is also known that salicylates have teratogenic effects.

Impairments in implantation, embryotoxic and fetotoxic effects, and learning disabilities in offspring have been reported following prenatal exposure to the drug.

Clinical characteristics.

Indications.

Prevention of thrombosis (prevention of reocclusion) after aortocoronary bypass grafting, percutaneous transluminal catheter angioplasty, and after arteriovenous shunting in patients undergoing dialysis.

Prevention of cerebrovascular stroke following transient ischemic attacks (TIA).

Reduction of the risk of coronary thrombosis after myocardial infarction (prevention of recurrent infarction).

Prevention of myocardial infarction in combination with other therapeutic measures in patients at very high risk of cardiovascular events (based on benefit-risk assessment by the treating physician).

Unstable angina.

Prevention of arterial thrombosis following vascular surgery.

As part of standard therapy for acute myocardial infarction.

Prevention of vascular occlusion in arterial occlusive disease.

Contraindications.

Hypersensitivity to acetylsalicylic acid, other salicylates, or other nonsteroidal anti-inflammatory drugs (NSAIDs), as well as to any component of the medicinal product.

Asthma induced by salicylates or substances with similar effects, 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 (see section "Interaction with other medicinal products and other forms of interaction").

Third trimester of pregnancy (see section "Use during pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

Concomitant use is contraindicated.

Concomitant use of acetylsalicylic acid and methotrexate at doses of 15 mg/week or higher increases hematological toxicity of methotrexate (due to decreased renal clearance of methotrexate caused by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates) (see section "Contraindications").

Combinations requiring caution.

Methotrexate at doses less than 15 mg/week: increased hematological toxicity of methotrexate (due to decreased renal clearance of methotrexate caused 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.

Acetylsalicylic acid (ASA) enhances the effects of anticoagulants/thrombolytic agents, barbiturates, lithium, sulfonamides, and triiodothyronine.

Pharmacodynamic interactions may occur between selective serotonin reuptake inhibitors (SSRIs) and acetylsalicylic acid: increased risk of bleeding due to synergistic effects.

ASA increases plasma digoxin concentrations due to reduced renal excretion.

ASA increases plasma levels of phenytoin and valproate. When used concomitantly with valproic acid, ASA displaces it from plasma protein binding, reducing its metabolism. As a result, plasma valproate levels increase, leading to a higher incidence of adverse reactions indicating intoxication, such as tremor, nystagmus, ataxia, and personality changes.

ASA enhances the action and side effects of all non-steroidal anti-rheumatic agents.

Concomitant use with NSAIDs such as ibuprofen or naproxen may attenuate the irreversible inhibition of platelets by acetylsalicylic acid. The clinical significance of this interaction is unknown. Treatment with NSAIDs such as ibuprofen or naproxen in patients at risk of cardiovascular disease may reduce the cardioprotective effect of acetylsalicylic acid (see section "Special precautions for use").

Antihypertensive agents (angiotensin-converting enzyme (ACE) inhibitors and β-blockers): if a patient is concurrently using acetylsalicylic acid and these medicinal products, careful monitoring of blood pressure is recommended, with dose adjustment if necessary.

Diuretics in combination with high doses of ASA: reduced diuretic efficacy.

ASA reduces the effect of uricosuric agents (e.g., probenecid, sulfinpyrazone).

Systemic glucocorticosteroids: increased risk of gastrointestinal ulcers and bleeding.

Decreased blood levels of salicylates during corticosteroid therapy; risk of salicylate overdose after discontinuation of glucocorticoid therapy.

Alcohol: increased risk of gastrointestinal ulcers and bleeding, prolonged bleeding time.

Prolonged plasma elimination half-life of penicillin.

Concomitant use of metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation. Therefore, this combination should be used with caution in patients taking acetylsalicylic acid at low cardioprotective doses.

Special precautions for use.

The medicinal product should be used with caution in the following situations:

• Impaired renal function or cardiovascular circulatory disorders (e.g. renal vascular disease, congestive heart failure, hypovolemia, major surgery, sepsis, or severe hemorrhage) — since acetylsalicylic acid may additionally increase the risk of renal impairment and acute renal failure;
• Impaired liver function;
• Concomitant use of NSAIDs, such as ibuprofen or naproxen — because NSAIDs may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. When acetylsalicylic acid is used prior to initiating NSAIDs as analgesics, the patient should consult a physician (see section "Interaction with other medicinal products and other forms of interaction");
• Presence of symptoms of chronic gastric or duodenal dyspepsia or its recurrence;
• Presence of bronchial asthma or general tendency to hypersensitivity — since acetylsalicylic acid may provoke bronchospasm or an asthma attack, as well as other hypersensitivity reactions. Risk factors include history of asthma, hay fever, nasal polyps, chronic respiratory diseases, or allergic reactions (such as rash, itching, or urticaria) to other agents in the past;
• Nasal polyps;
• Severe glucose-6-phosphate dehydrogenase deficiency — since acetylsalicylic acid may cause hemolysis or hemolytic anemia. Factors that may increase the risk of hemolysis include high drug doses, fever, or acute infectious processes;
• 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 severity of bleeding during surgical procedures (including minor surgeries, e.g. tooth extraction);
• Use of acetylsalicylic acid in children and adolescents with fever and/or viral infections should only be done under medical supervision as second-line therapy (due to the risk of Reye’s syndrome, a life-threatening encephalopathy characterized primarily by severe vomiting, loss of consciousness, and hepatic dysfunction).

When used in low doses, ASA reduces the excretion of uric acid. In patients who normally have reduced uric acid excretion, this may lead to the development of gout.

With certain viral infections, particularly influenza A, influenza B, and varicella, there is a risk of developing Reye’s syndrome — a very rare but life-threatening condition requiring immediate medical intervention. The risk may be increased if acetylsalicylic acid is used concomitantly; 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;

• Gastrointestinal ulcers, including chronic or recurrent peptic ulcer disease or gastrointestinal bleeding in medical history;
• Hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents, as well as allergy to other substances.

Use during pregnancy or breastfeeding.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological studies indicate an increased risk of miscarriage and congenital heart defects and gastroschisis following the use of prostaglandin synthesis inhibitors early in pregnancy. The risk increases with higher doses and longer duration of treatment.

Epidemiological data do not confirm an association between acetylsalicylic acid use and an increased risk of miscarriage. Available data on miscarriage are inconsistent; however, an increased risk of gastroschisis cannot be ruled out with acetylsalicylic acid use. Results from prospective studies on drug exposure during early pregnancy (months 1–4) do not indicate any association with an increased risk of malformations.

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

Animal studies have shown that the use of prostaglandin inhibitors leads to increased pre- and post-implantation losses and embryo/fetal death. In addition, a higher incidence of severe developmental abnormalities, including cardiovascular malformations, has been observed in animals treated with prostaglandin inhibitors during organogenesis.

Based on previous experience, the risk is considered low when the medicinal product is used at therapeutic doses.

All prostaglandin synthesis inhibitors may affect:

• the fetus:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

• impaired renal function, potentially leading to renal failure with oligohydramnios;

• the mother and the fetus:

• prolonged bleeding time, anti-aggregatory effect, which may occur even with very low doses;

• inhibition of uterine contractions, bleeding in the pregnant woman, and prolonged duration of labor.

Because of these effects, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.

Breastfeeding. Salicylates are excreted into breast milk. Concentrations in breast milk are equivalent to or even higher than plasma concentrations in the mother.

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

Ability to affect reaction speed when driving or operating machinery.

There is no information available regarding the effects of the medicinal product on the ability to drive or operate machinery.

Method of Administration and Dosage

Unless otherwise prescribed by a physician, the following dosage regimen is recommended.

Cardiovascular indications without coronary artery bypass grafting or percutaneous transluminal coronary angioplasty: 1 × 100 mg/day.

Prophylaxis of thrombosis following coronary artery bypass grafting or percutaneous transluminal coronary angioplasty: 100–300 mg/day.

Prophylaxis of cerebrovascular stroke after onset of warning signs (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 food intake. Drink ½–1 glass of water. To prevent premature release of the active substance before reaching the alkaline environment of the intestine, the tablets must not be crushed, broken, or chewed.

Acute myocardial infarction: in cases of acute myocardial infarction, administer 200–300 mg of acetylsalicylic acid intravenously or orally in a form allowing rapid release of acetylsalicylic acid (not enteric-coated formulation). Enteric-coated acetylsalicylic acid tablets should be crushed or chewed prior to administration to achieve faster absorption. Thereafter, 100 mg of acetylsalicylic acid should be administered daily.

Children.

The medicinal product is not recommended for use in children and adolescents (under 18 years of age) due to lack of data on efficacy and safety in this patient population.

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). Please refer to the information provided in the section "Special Warnings and Precautions for Use."

Overdose.

Severe intoxication may be life-threatening. Neonates are more sensitive than adults. Symptoms of severe poisoning may develop acutely or gradually, for example within 12–24 hours after administration. Following oral administration, doses of ASA up to 150 mg/kg body weight may lead to moderate intoxication, while doses > 300 mg/kg body weight may result in severe intoxication.

Absorption of acetylsalicylic acid may be delayed due to delayed gastric emptying, formation of concretions in the stomach, or when the drug is administered in enteric-coated tablet form.

The severity of intoxication cannot be assessed solely based on plasma salicylate concentrations. Careful monitoring of the patient’s condition using arterial blood gas analysis (ABGA) is required, as therapy is based not on blood salicylate levels but on clinical symptoms and ABGA findings.

Warnings.

Local signs of irritation, which typically predominate in ASA overdose—such as nausea, vomiting, and stomach pain—may be absent, as this pharmaceutical 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 disturbances, tremor, confusion, hyperthermia, excessive sweating, hyperventilation, respiratory alkalosis with metabolic compensation leading to metabolic acidosis, electrolyte imbalance, dehydration, seizures, coma, respiratory distress syndrome, cardiac arrhythmia.

Symptoms of chronic salicylate intoxication are nonspecific (e.g., tinnitus, headache, irritability, excessive sweating, hyperventilation) and may therefore remain unnoticed.

Management.

Due to potentially life-threatening conditions in severe intoxication, all necessary emergency measures should be initiated immediately: immediate hospitalization, prevention or reduction of absorption by administering appropriate doses of activated charcoal within the first 4 hours (activated charcoal in a 10-fold amount relative to the ingested ASA); in cases of severe intoxication—gastric lavage or endoscopic removal of tablets.

Appropriate monitoring and correction of electrolytes. Administration of glucose and sodium bicarbonate in early stages to correct acidosis and enhance elimination (urine pH > 8), improvement of diuresis, cooling in case of hyperthermia, benzodiazepines for seizures.

Hemodialysis may be considered in cases of severe intoxication.

Cases of decompensation leading to fatal outcomes after intubation have been reported. Therefore, if possible, intubation should be performed after initiation of alkalization, apnea time should be minimized, and hyperventilation should be maintained.

Detailed information can be obtained from a toxicology center.

Adverse Reactions

Adverse reactions are listed below by frequency: very common: ≥ 1/10; common: ≥ 1/100 to < 1/10; uncommon: ≥ 1/1000 to < 1/100; rare: ≥ 1/10,000 to < 1/1000; very rare: < 1/10,000. Within each frequency group, adverse reactions are presented in order of decreasing severity.

Additional adverse reactions have been reported spontaneously during the use of all dosage forms of acetylsalicylic acid, including short-term and long-term oral therapy; therefore, frequency cannot be estimated.

In patients with severe forms of glucose-6-phosphate dehydrogenase deficiency, hemolysis and hemolytic anemia have been observed.

Due to the antiplatelet effect of acetylsalicylic acid (ASA), the risk of bleeding may be increased. Bleeding events observed include perioperative bleeding, hematoma, epistaxis, urogenital bleeding, and gingival bleeding.

Serious bleeding events, such as gastrointestinal hemorrhage and hemorrhagic stroke, have been observed rarely or very rarely, particularly in patients with uncontrolled arterial hypertension and/or concomitant use of anticoagulants, which in some cases may be life-threatening.

Blood and lymphatic system disorders:

Prolongation of bleeding time;

Rare: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia, iron-deficiency anemia.

Immune system disorders:

Uncommon: asthma;

Rare: hypersensitivity reactions such as erythematous/eczematous skin reactions, urticaria, rhinitis, nasal congestion, bronchospasm, angioedema, hypotension progressing to shock;

Very rare: severe skin reactions including exudative multiform erythema, Stevens–Johnson syndrome, toxic epidermal necrolysis.

Metabolism and nutrition disorders:

Very rare: hypoglycemia, acid-base imbalance.

Nervous system disorders:

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

Gastrointestinal disorders:

Very common: microbleeding (70%);

Common: gastric symptoms;

Uncommon: dyspepsia, nausea, vomiting, diarrhea;

Rare: gastrointestinal hemorrhage, gastrointestinal ulcers, which in very rare cases may lead to perforation.

Hepatobiliary disorders:

Rare: hepatic dysfunction;

Very rare: increased transaminase levels.

Renal and urinary disorders:

Rare: renal function impairment;

Cases of acute renal failure have been reported.

Other:

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

Bleeding 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.

Gastrointestinal disorders such as general symptoms and signs of dyspepsia, epigastric pain, and abdominal pain; in individual cases – inflammation of the gastrointestinal tract, erosive-ulcerative lesions of the gastrointestinal tract, which in rare cases may result in gastrointestinal hemorrhage and perforation, with corresponding laboratory and clinical manifestations.

Hypersensitivity reactions with corresponding laboratory and clinical manifestations include asthmatic attacks, mild to moderate skin reactions, and reactions involving the respiratory, gastrointestinal, and cardiovascular systems, including symptoms such as rash, swelling, pruritus, cardiorespiratory failure, and very rarely, severe reactions including anaphylactic shock.

Shelf life. 2 years from the date of manufacture of the bulk product.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

100 mg tablets: № 10×2, № 10×3 in blisters in a carton.

300 mg tablets: № 10×2 in blisters in a carton.

Pharmaceutical category.

Over-the-counter (without prescription).

Manufacturer.

Limited liability company "Pharmaceutical Company "Vertex".

Address of manufacturer and location of business activity.

33, Astronomichna Street, lit. "V-1", Kharkiv, Kharkiv region, 61085, Ukraine.