INSTRUCTION for medical use of the medicinal product AСK-Teva (ASK-Teva)

Composition:

Active substance: acetylsalicylic acid;

1 tablet contains 75 mg or 100 mg of acetylsalicylic acid;

Excipients: microcrystalline cellulose (type 102), corn starch, colloidal anhydrous silicon dioxide, stearic acid;

coating: methacrylic acid copolymer dispersion, polysorbate 80, sodium lauryl sulfate, triethyl citrate, talc.

Pharmaceutical form. Enteric-coated tablets.

Main physicochemical properties:

75 mg tablets: white, oval, biconvex, enteric-coated tablets, 9.2×5.2 mm in size;

100 mg tablets: white, round, biconvex, enteric-coated tablets, 7.2 mm in diameter.

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 recognized that acetylsalicylic acid exerts other inhibitory effects on platelets, which justify its use in various vascular diseases.

Repeated administration of doses ranging from 20 to 325 mg results in enzyme activity inhibition between 30% and 95%.

Due to the irreversible nature of binding, the effect persists throughout the lifespan of platelets (7–10 days). The inhibitory effect does not cease during prolonged treatment, and enzymatic activity gradually resumes as new platelets are formed, typically within 24–48 hours after discontinuation of the drug.

Acetylsalicylic acid increases bleeding time by an average of 50–100%, although individual variations should be taken into account.

Experimental data suggest that ibuprofen may interfere with the antiplatelet effect of low-dose acetylsalicylic acid when both are administered concomitantly.

In one study, a single 400 mg dose of ibuprofen administered within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg) reduced the effect of acetylsalicylic acid on thromboxane formation and platelet aggregation. However, due to the limited nature of these data and uncertainty regarding the extrapolation of ex vivo findings to clinical settings, definitive conclusions about regular ibuprofen use cannot be drawn. Occasional use of ibuprofen is unlikely to result in clinically relevant interactions.

Acetylsalicylic acid belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and possesses analgesic, antipyretic, and anti-inflammatory properties. When administered orally in higher doses, acetylsalicylic acid is used to relieve pain and mild febrile conditions such as cold and flu, to reduce fever, and to alleviate joint and muscle pain, as well as in acute and chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.

Pharmacokinetics.

Absorption

After oral administration, acetylsalicylic acid is rapidly and completely absorbed from the gastrointestinal tract. The primary site of absorption for enteric-coated tablets is the proximal segment of the small intestine. However, a significant portion of ASA is already hydrolyzed to salicylic acid within the intestinal wall during the absorption process. The extent of hydrolysis depends on the rate of absorption.

Maximum plasma concentrations of acetylsalicylic acid and salicylic acid are reached approximately 5 and 6 hours, respectively, after administration on an empty stomach. If tablets are taken with food, peak plasma concentrations of acetylsalicylic acid and salicylic acid are delayed by about 3 hours compared to administration on an empty stomach.

Distribution

Acetylsalicylic acid, as well as its primary metabolite—salicylic acid—is highly bound to plasma proteins, primarily albumin, and rapidly distributed throughout the body. The degree of salicylic acid binding to proteins is strongly dependent on both albumin and salicylic acid concentrations. The volume of distribution of acetylsalicylic acid is approximately 0.16 L/kg body weight. Salicylic acid slowly diffuses into synovial fluid, crosses the placenta, and is excreted into breast milk.

Biotransformation

Acetylsalicylic acid is rapidly metabolized to salicylic acid, with a half-life of 15–30 minutes. Metabolites of salicylic acid include salicyluric acid, phenolic and acyl glucuronides of salicylic acid, gentisic acid, and gentisuric acid.

The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by hepatic enzyme capacity. The elimination half-life increases from 2–3 hours at low doses, to 12 hours with standard analgesic doses, and up to 15–30 hours after high therapeutic or toxic doses.

Excretion

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

Preclinical Data

The preclinical safety profile of acetylsalicylic acid is well documented. In animal studies, salicylates did not cause any organ toxicity other than renal damage at high doses.

Acetylsalicylic acid has been extensively studied in vitro and in vivo for mutagenicity, with no evidence of mutagenic potential found. Similarly, studies on carcinogenicity have shown no such risk.

Salicylates have demonstrated teratogenic effects in animal studies across various species. Adverse effects observed include implantation disturbances, embryotoxic and fetotoxic effects, and impaired learning ability in offspring following prenatal exposure.

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 procedures (percutaneous transluminal coronary angioplasty (PTCA), carotid endarterectomy, aortocoronary bypass (CABG), arteriovenous shunting);
deep vein thrombosis and pulmonary embolism following prolonged immobilization (after surgical procedures);
strokes (as secondary prevention).

Contraindications.

Hypersensitivity to acetylsalicylic acid, other salicylates or inhibitors of prostaglandin synthetase, or to any component of the medicinal product.
History of asthma or angioneurotic edema induced by salicylates or substances with similar action, particularly NSAIDs.
Acute peptic ulcers and peptic ulcer relapses, including in medical history, and/or gastrointestinal bleeding or other types of bleeding such as cerebrovascular.
Hemorrhagic diathesis, coagulation disorders such as hemophilia and thrombocytopenia.
Severe hepatic insufficiency, liver cirrhosis.
Severe renal insufficiency (glomerular filtration rate <30 mL/min).
Severe heart failure.
Third trimester of pregnancy (see section "Use in pregnancy or lactation").
Combination with methotrexate at doses of 15 mg/week or higher (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Contraindicated combinations

Methotrexate (at doses >15 mg/week)

When used with methotrexate at doses of 15 mg/week or higher, hematological toxicity of methotrexate increases (due to decreased renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates). Therefore, concomitant use of methotrexate (at doses >15 mg/week) with acetylsalicylic acid is contraindicated.

Not recommended combinations

Uricosuric agents (e.g., probenecid, sulfinpyrazone)

Concomitant use of salicylates with probenecid reduces uric acid excretion effect (due to competition for renal tubular excretion of uric acid). Acetylsalicylic acid reduces uric acid excretion even at low doses. This may provoke gout development in patients with impaired uric acid excretion. Therefore, such combinations should be avoided.

Combinations requiring caution

Anticoagulants such as coumarins, heparin, warfarin

Risk of bleeding increases due to platelet function inhibition, damage to duodenal mucosa, and displacement of oral anticoagulants from plasma protein binding by salicylates. Coagulation time must be monitored (see section "Special precautions for use").

Antiplatelet agents (e.g., ticlopidine, clopidogrel, or dipyridamole) and selective serotonin reuptake inhibitors (SSRIs; e.g., sertraline, paroxetine)

Increased risk of gastrointestinal bleeding (see section "Special precautions for use"). If this combination is necessary, careful clinical and laboratory monitoring (including blood coagulation time) should be ensured.

Antidiabetic agents (insulin, sulfonylurea-containing drugs)

Salicylates may enhance the hypoglycemic effect of antidiabetic agents.

Digoxin and lithium

When used concomitantly with digoxin and lithium, their plasma concentrations increase due to reduced renal excretion. Plasma concentrations of digoxin and lithium should be monitored at the beginning and throughout the treatment period with acetylsalicylic acid. Dose adjustment may be required.

Barbiturates

Serum barbiturate concentration may increase when used concomitantly with acetylsalicylic acid.

Aldosterone antagonists, loop diuretics

The effectiveness of aldosterone antagonists (e.g., spironolactone) and loop diuretics may be reduced when used concomitantly with acetylsalicylic acid.

Diuretics and antihypertensive agents

NSAIDs may reduce the antihypertensive effect of diuretics and other antihypertensive agents (angiotensin-converting enzyme (ACE) inhibitors and β-blockers). Concomitant use of ACE inhibitors/angiotensin II antagonists with cyclooxygenase inhibitors may lead to impaired renal function in patients with pre-existing renal dysfunction (e.g., dehydrated patients and elderly patients). This may result in acute renal failure, which is usually reversible. Caution is recommended when using NSAIDs in combination with ACE inhibitors/angiotensin II antagonists, especially in elderly patients. Patients should receive adequate fluid intake, and monitoring of renal function should be considered at the start of combined therapy and at regular intervals during treatment.

Diuretics: risk of acute renal failure due to decreased glomerular filtration resulting from reduced renal prostaglandin synthesis. At the beginning of treatment, patient hydration and monitoring of renal function are recommended. Patients receiving concomitant acetylsalicylic acid and these medicinal products should have careful monitoring of blood pressure and dose adjustment as needed.

Carbonic anhydrase inhibitors (acetazolamide)

May lead to severe cases of acidosis and increased neurotoxicity.

Systemic corticosteroids

Risk of ulcers and gastrointestinal bleeding may increase when acetylsalicylic acid is used concomitantly with corticosteroids.

Methotrexate (at doses <15 mg/week)

When used with methotrexate at doses less than 15 mg/week, hematological toxicity of methotrexate increases (due to decreased renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates). Blood tests should be performed weekly during the first weeks of treatment.

Patients with renal impairment, even mild, and elderly patients require careful monitoring.

Other NSAIDs

Due to synergistic effects, the risk of ulcers and gastrointestinal bleeding increases.

ibuprofen

Concomitant use of acetylsalicylic acid with ibuprofen interferes with irreversible platelet inhibition by acetylsalicylic acid. Treatment with ibuprofen in patients at risk of cardiovascular disease may reduce the cardioprotective effect of acetylsalicylic acid.

Metamizole

When used concomitantly with acetylsalicylic acid, metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation. Therefore, caution is recommended when using acetylsalicylic acid (as a cardioprotector) and metamizole together.

Cyclosporine, tacrolimus

Concomitant use of NSAIDs with cyclosporine or tacrolimus may increase the nephrotoxic effects of the latter. Renal function should be monitored when this combination is used.

Sodium valproate/valproic acid

When used concomitantly with valproates, acetylsalicylic acid displaces them from plasma protein binding, leading to increased serum valproate concentrations and enhanced clinical and adverse effects.

Sulfonamides and triiodothyronine

Enhanced effects of sulfonamides and triiodothyronine.

Penicillin

Prolongation of penicillin plasma half-life.

Phenytoin

Salicylates reduce phenytoin binding to plasma albumin. This may lead to decreased total phenytoin levels in plasma and increased fraction of free phenytoin. However, the concentration of unbound phenytoin and thus the therapeutic effect remain essentially unchanged.

Alcohol

Increased risk of gastrointestinal bleeding and prolonged bleeding time due to synergistic action of acetylsalicylic acid and alcohol.

Special precautions for use.

Acetylsalicylic acid in doses of 75 mg and 100 mg is not used as an analgesic-antipyretic or anti-inflammatory agent.

Recommended for use in adults. Acetylsalicylic acid may cause Reye's syndrome in some children. Reye's syndrome may occur when medications containing acetylsalicylic acid are administered to children with acute respiratory viral infections (ARVI), with or without fever, without prior medical consultation. In certain viral diseases, 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. The drug is not recommended for use in children unless the expected benefit outweighs the risks. Only a physician may prescribe acetylsalicylic acid to children when other measures prove insufficient.

The risk of bleeding is particularly increased during or after surgical procedures (including minor surgeries such as tooth extraction) due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after administration of acetylsalicylic acid-containing medications. Therefore, caution is required prior to surgical procedures, including dental procedures. Temporary discontinuation of therapy may be necessary.

Acetylsalicylic acid is not recommended for use in cases of menorrhagia, as it may exacerbate menstrual bleeding.

Use with caution in patients with hypertension and in patients with a history of gastric or duodenal ulcers, bleeding, or those undergoing anticoagulant therapy.

The drug should be used with caution in patients with gastrointestinal disorders, presence of symptoms of chronic gastric or duodenal dyspepsia, or their recurrence.

Patients should inform their physician about any unusual bleeding. In case of gastrointestinal bleeding or ulcerogenic effects, treatment with the drug should be discontinued.

The drug should be used with caution in patients with moderate renal impairment (severe impairment is a contraindication) or disorders of cardiovascular circulation (e.g., renal vascular pathology, congestive heart failure, hypovolemia, major surgery, sepsis, or severe bleeding), as acetylsalicylic acid may also increase the risk of impaired kidney function and acute renal failure.

The drug should be used with caution in patients with moderate hepatic impairment (severe impairment is a contraindication) or liver diseases. Patients with mild or moderate hepatic impairment should undergo regular liver function tests.

The medicinal product should be used with caution in patients with bronchial asthma, nasal polyps, or a general tendency to hypersensitivity, as acetylsalicylic acid may induce bronchospasm, asthma attacks, 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.

Serious skin reactions, including Stevens-Johnson syndrome, have been rarely reported in association with acetylsalicylic acid use (see section "Adverse reactions"). If skin rashes, mucosal lesions, or other signs of hypersensitivity occur, treatment with acetylsalicylic acid should be discontinued.

The drug should be used with caution in patients with hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents, as well as allergy to other substances.

The drug should be used with caution in patients with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, as 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.

Elderly patients are particularly susceptible to adverse reactions when using NSAIDs, including acetylsalicylic acid, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "Dosage and administration"). If long-term therapy with acetylsalicylic acid is required, such patients should undergo regular medical examinations.

Concomitant use of acetylsalicylic acid with other medicinal products affecting hemostasis (e.g., anticoagulants such as warfarin, thrombolytics, antiplatelet agents, anti-inflammatory drugs, and selective serotonin reuptake inhibitors) is not recommended, except when such combination is strictly indicated, due to the possible increased risk of bleeding (see section "Interaction with other medicinal products and other forms of interaction"). If such combination cannot be avoided, careful monitoring/observation of the patient for signs of bleeding is recommended.

Regular use of acetylsalicylic acid may worsen the prognosis in patients with intracerebral hemorrhage. Therefore, patients at increased risk of intracerebral hemorrhage, such as those with high arterial blood pressure, should be monitored when receiving acetylsalicylic acid. Additionally, use of acetylsalicylic acid has been associated with an increased risk of intracerebral hemorrhage in patients with a tendency to nosebleeds.

If prolonged vomiting, loss of consciousness, or abnormal behavior occurs during treatment with acetylsalicylic acid, administration of the drug should be discontinued.

Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. If acetylsalicylic acid is used before starting ibuprofen for pain relief, the patient should consult a physician (see section "Interaction with other medicinal products and other forms of interaction").

Caution is recommended when concomitantly using medicinal products that increase the risk of ulcerogenic effects, such as oral corticosteroids, selective serotonin reuptake inhibitors, and deferasirox (see section "Interaction with other medicinal products and other forms of interaction").

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

Acetylsalicylic acid, when used in high doses, may potentiate the effect of sulfonylureas and insulin, increasing the risk of hypoglycemia (see section "Interaction with other medicinal products and other forms of interaction").

Use of acetylsalicylic acid may impair fertility in women and is not recommended for women planning pregnancy. For women experiencing conception difficulties or undergoing fertility investigations, discontinuation of acetylsalicylic acid therapy should be considered.

Use during pregnancy or breastfeeding.

Pregnancy

Salicylates should be used with caution during the first and second trimesters of pregnancy. Use of salicylates is contraindicated during the third trimester of pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and fetal malformations (cardiac defects and gastroschisis) following use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with higher doses and longer duration of treatment.

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

During the first and second trimesters of pregnancy, acetylsalicylic acid-containing medications should not be prescribed without clear clinical necessity. For women who may be pregnant or for patients in the first and second trimesters of pregnancy, the dose of acetylsalicylic acid-containing medications 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 child learning ability have been reported following prenatal exposure to salicylates.

Animal studies indicate that salicylate use causes adverse effects in the fetus (such as increased mortality, growth disorders, salicylate intoxication), but controlled studies in pregnant women have not been conducted.

Based on previous experience, the risk is low when the drug is used at therapeutic doses.

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) and/or impaired kidney function, potentially leading to renal failure with oligohydramnios;

− prolonged bleeding time, antiplatelet effect, which may occur in both the mother and the fetus near the end of pregnancy;

− prolonged bleeding time may also occur with very low doses;

− inhibition of uterine contractions and maternal bleeding, and prolonged duration of labor.

Therefore, 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 those in maternal plasma.

In cases of medically necessary use during lactation, breastfeeding should be discontinued if high doses (>300 mg/day) are used regularly.

Ability to influence reaction speed when driving vehicles or operating machinery.

No studies have been conducted.

Dosage and Administration.

For oral use.

Tablets should be swallowed whole with an adequate amount of liquid (1/2 glass of water). Tablets should not be crushed, split, or chewed, as the enteric coating of the tablet prevents the irritating effect of the drug on the intestine.

To reduce the risk of death in patients with suspected acute myocardial infarction, administer the drug at a dose of 75–300 mg daily. Continue with a maintenance dose of 75–300 mg daily for 30 days after the infarction. After 30 days, consider further prophylaxis for prevention of recurrent myocardial infarction.

If an enteric-coated tablet is used for this indication, the initial dose should be chewed to achieve rapid absorption.

To reduce the risk of morbidity and mortality in patients who have suffered myocardial infarction, administer 75–300 mg daily.

For secondary prevention of stroke, administer the drug at a dose of 75–300 mg daily.

To reduce the risk of transient ischemic attack (TIA) and stroke in patients with TIA, administer 75–300 mg daily.

To reduce the risk of disease and death in patients with stable and unstable angina, administer 75–300 mg daily.

For prophylaxis of thromboembolic events after vascular procedures (percutaneous transluminal coronary angioplasty [PTCA], carotid endarterectomy, coronary artery bypass grafting [CABG], arteriovenous shunting), administer the drug at a dose of 75–150 mg daily or 300 mg every other day.

For prophylaxis of deep vein thrombosis and pulmonary embolism after prolonged immobilization (following surgical procedures), administer 75–150 mg daily or 300 mg every other day.

To reduce the risk of myocardial infarction in patients at high risk of cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and in patients with multifactorial risk of cardiovascular disease (hyperlipidemia, obesity, smoking, advanced age), administer 75 mg daily or 300 mg every other day.

Elderly patients

Elderly patients are generally more susceptible to adverse reactions; therefore, acetylsalicylic acid should be used with caution in this patient group. In the absence of severe renal or hepatic impairment, the drug may be administered at standard adult doses. Treatment should be reviewed regularly (see section "Special precautions").

Children

The medicinal product is not intended for use in children.

Administration of acetylsalicylic acid to children under 16 years of age may cause serious adverse effects (see section "Special precautions").

Overdose.

Symptoms of severe poisoning may develop slowly, for example, within 12–24 hours after administration. After oral administration of acetylsalicylic acid (ASA) at doses up to 150 mg/kg body weight, moderate intoxication may occur; at doses >300 mg/kg body weight, severe intoxication may occur.

Chronic salicylate poisoning may have an insidious course, as its symptoms are nonspecific. Moderate chronic intoxication usually occurs only after repeated intake of large doses.

Acute intoxication is characterized by significant 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, formation of gastric concretions, or if the drug is taken in enteric-coated tablet form.

Warning.

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, hypocalcemia, hypokalemia, hyper-/hypoglycemia, skin rash, dizziness, gastrointestinal bleeding, inhibition of thrombosis progressing to coagulopathy, cardiovascular disorders (from arrhythmia and arterial hypotension to cardiac arrest), tinnitus, visual and hearing disturbances, tremor, confusion, hyperthermia, increased sweating, hyperventilation, acid-base imbalance and electrolyte disturbances, dehydration, seizures, rhabdomyolysis, pulmonary edema, coma, and respiratory failure.

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

Treatment.

There is no specific antidote. Due to life-threatening conditions caused by severe intoxication, all necessary preventive measures should be taken 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 and fluid balance, thermoregulation correction, respiratory support. Administration of glucose. Sodium bicarbonate for correction of acidosis and to enhance elimination (urine pH >8). Glycine: initial dose – 8 g orally, followed by 4 g every 2 hours for 16 hours. Hemoperfusion or hemodialysis may be considered (the need for such treatment may be determined at a toxicology center).

Side effects.

Blood and lymphatic system disorders:

Prolongation of bleeding time;

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

Immune system disorders:

Uncommon: asthma;

Isolated cases: hypersensitivity reactions such as erythematous/eczematous skin reactions, urticaria, rhinitis, nasal congestion, bronchospasm, angioneurotic edema, angioedema, anaphylactic reactions, decreased blood pressure leading to shock;

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

Metabolism and nutrition disorders:

Rare: hypoglycemia, iron deficiency anemia, acid-base imbalance; frequency not known: hyperuricemia.

Nervous system disorders:

Isolated cases: headache, dizziness, vertigo, tinnitus, visual disturbances, hearing disturbances, confusion.

Vascular disorders:

Rare: hemorrhagic vasculitis.

Respiratory, thoracic and mediastinal disorders:

Uncommon: rhinitis, dyspnea.

Reproductive system and breast disorders:

Rare: menorrhagia.

Skin and subcutaneous tissue disorders:

Rare: purpura, nodular erythema.

Gastrointestinal disorders:

Common: microbleeding (70%), gastrointestinal symptoms, abdominal pain, heartburn;

Uncommon: dyspepsia, nausea, vomiting, diarrhea;

Isolated cases: gastrointestinal bleeding, gastrointestinal ulcers, which in very rare cases may lead to perforation, with corresponding clinical symptoms and laboratory changes.

Hepatobiliary disorders:

Isolated cases: hepatic dysfunction (e.g., elevated transaminase levels); frequency not known: hepatic failure.

Renal and urinary disorders:

Impaired kidney function and development of acute renal failure have been reported.

Other:

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

In spontaneous reports, information has been received about other adverse reactions related to all dosage forms of acetylsalicylic acid (ASA), including during short-term and long-term oral therapy; therefore, classification of frequency according to CIOMS III is not possible.

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

Due to the antiplatelet effect, ASA use may increase the risk of bleeding. Bleeding events such as perioperative bleeding, hematomas, epistaxis, urogenital bleeding, and gingival bleeding have been observed. Symptoms may persist for 4–8 days after discontinuation of acetylsalicylic acid.

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

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 – gastrointestinal tract inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which potentially may in isolated cases lead to gastrointestinal hemorrhages and perforations, with corresponding laboratory parameters and clinical manifestations.

Hypersensitivity reactions with corresponding laboratory and clinical manifestations include asthmatic state, mild to moderate skin reactions, as well as involvement of 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.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets in a blister; 3 blisters in a cardboard box.

Prescription status. Over-the-counter.

Manufacturer. Balkanpharma-Dupnitsa AD / Balkanpharma-Dupnitsa AD.

Manufacturer's address and location of operations.

3 Samokovsko Shosse Street, Dupnitsa, 2600, Bulgaria / 3 Samokovsko Shosse Street, Dupnitsa, 2600, Bulgaria.

Ask-teva