Instructions for use of ASA-Teva tablets 75mg No. 30
Composition
active ingredient: 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;
shell: methacrylate copolymer dispersion, polysorbate 80, sodium lauryl sulfate, triethyl citrate, talc.
Dosage form
Enteric-coated tablets.
Main physicochemical properties:
75 mg tablets: white, oval, biconvex, enteric-coated tablets, measuring 9.2×5.2 mm;
100 mg tablets: white, round, biconvex, enteric-coated tablets, 7.2 mm in diameter.
Pharmacotherapeutic group
Antithrombotic agents.
ATX code B01A C06.
Pharmacological properties
Pharmacodynamics.
Acetylsalicylic acid (ASA) inhibits platelet aggregation by blocking the synthesis of thromboxane A2. Its mechanism of action is the irreversible inactivation of the enzyme cyclooxygenase (COX-1). This inhibitory effect is particularly pronounced for platelets, since they are unable to resynthesize this enzyme. It is also recognized that acetylsalicylic acid has other inhibitory effects on platelets, due to which it is used in many vascular diseases.
Repeated administration of doses of 20-325 mg leads to inhibition of enzymatic activity from 30 to 95%.
Due to the irreversible nature of the binding, the effect persists for the life span of platelets (7-10 days). The inhibitory effect does not cease during prolonged treatment and enzymatic activity gradually resumes after platelet recovery within 24-48 hours after discontinuation of drug treatment.
Acetylsalicylic acid increases bleeding time by an average of 50-100%, but individual differences should be taken into account.
Experimental data suggest that ibuprofen may inhibit the effect of low doses of acetylsalicylic acid on platelet aggregation when used concomitantly.
In one study, when a single dose of ibuprofen 400 mg was taken within 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid (81 mg), the effect of acetylsalicylic acid on thromboxane formation or platelet aggregation was reduced. However, due to the limitations of these data and the uncertainty regarding the extrapolation of ex vivo data to the clinical situation, no firm conclusions can be drawn regarding regular use of ibuprofen, and with occasional use of ibuprofen, clinically relevant effects are unlikely to occur.
Acetylsalicylic acid belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesic, antipyretic and anti-inflammatory properties. Orally, in higher doses, acetylsalicylic acid is used to relieve pain and mild febrile conditions such as colds and flu, to reduce fever and relieve joint and muscle pain, in acute and chronic inflammatory diseases 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 main site of absorption of acetylsalicylic acid (enteric-coated tablets) is the proximal small intestine. However, a significant part of ASA is hydrolyzed to salicylic acid already in the intestinal wall during absorption. The degree of hydrolysis depends on the rate of absorption.
The maximum concentration of acetylsalicylic acid and salicylic acid in the blood plasma is reached 5 and 6 hours after administration on an empty stomach, respectively. If the tablets are taken with food, the maximum concentration of acetylsalicylic acid and salicylic acid in the blood plasma is reached 3 hours later than after administration on an empty stomach.
Distribution
Acetylsalicylic acid, as well as the main metabolite - salicylic acid, are largely bound to blood plasma proteins, mainly albumin, and are rapidly distributed in the body. The degree of binding of salicylic acid to proteins strongly depends on the concentration of albumin and salicylic acid. The volume of distribution of acetylsalicylic acid is approximately 0.16 l/kg body weight. Salicylic acid slowly diffuses into the synovial fluid, penetrates the placenta and is excreted in breast milk.
Biotransformation
Acetylsalicylic acid is rapidly metabolized to salicylic acid, with a half-life of 15-30 minutes. The metabolites of salicylic acid are salicyluric acid, phenolic and acyl glucuronides of salicylic acid, gentisic acid and gentisinuric acid.
The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by liver enzyme activity. The elimination half-life is dose-dependent and increases from 2-3 hours at low doses, to 12 hours at usual analgesic doses, and to 15-30 hours after high therapeutic or toxic doses.
Breeding
Salicylic acid and its metabolites are excreted from the body mainly by the kidneys.
The preclinical safety profile of acetylsalicylic acid is well documented. In animal studies, salicylates at high doses did not cause any other organic lesions than renal lesions.
Acetylsalicylic acid has been extensively studied in vitro and in vivo for mutagenicity, but no evidence of mutagenic potential has been found. The same applies to carcinogenicity studies.
Salicylates have been shown to be teratogenic in studies in various animal species. Implantation disorders, embryotoxic and fetotoxic effects, and learning disorders have been described in the offspring after prenatal use of the drug.
Indication
To reduce risk:
death in patients with suspected acute myocardial infarction;
morbidity and mortality in patients who have had myocardial infarction;
transient ischemic attacks (TIA) and stroke in patients with TIA;
morbidity and mortality in stable and unstable angina;
myocardial infarction in patients with a high risk of developing cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and in patients with a multifactorial risk of cardiovascular disease (hyperlipidemia, obesity, smoking, old age).
For prevention:
thrombosis and embolism after vascular surgery (percutaneous transluminal catheter angioplasty (PTCA), carotid endarterectomy, coronary artery bypass grafting (CABG), arteriovenous bypass grafting);
deep vein thrombosis and pulmonary embolism after long-term immobilization (after surgery);
strokes (as secondary prevention).
Contraindication
Hypersensitivity to acetylsalicylic acid, other salicylates or prostaglandin synthetase inhibitors or to any component of the drug.
History of asthma or angioedema induced by salicylates or substances with similar effects, especially NSAIDs.
Acute peptic ulcers and recurrent peptic ulcers, including a history, and/or gastric/intestinal bleeding or other types of bleeding, such as cerebrovascular.
Hemorrhagic diathesis, coagulation disorders such as hemophilia and thrombocytopenia.
Severe liver failure, cirrhosis of the liver.
Severe renal failure (glomerular filtration rate <30 ml/h).
Severe heart failure.
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Combination with methotrexate at a dosage of 15 mg/week or more (see section “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Contraindicated combinations
Methotrexate (at a dosage of >15 mg/week)
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). Therefore, the simultaneous use of methotrexate (at doses >15 mg/week) with acetylsalicylic acid is contraindicated.
Not recommended combinations
Uricosuric agents (such as probenecid, sulfinpyrazone)
Concomitant use of salicylates with probenecid reduces the effect of uric acid excretion (due to competition for uric acid excretion by the renal tubules). Acetylsalicylic acid reduces uric acid excretion even at low doses. This may provoke the development of gout in patients with reduced uric acid excretion. Therefore, the combination of drugs should be avoided.
Combinations to be used with caution
Anticoagulants such as coumarin, heparin, warfarin
The risk of bleeding increases because platelet function is suppressed, the duodenal mucosa is damaged, and oral anticoagulants are displaced by salicylates from plasma protein binding. Blood coagulation time should be monitored (see section "Special warnings and precautions for use").
Antiplatelet agents (such as ticlopidine, clopidogrel, or dipyridamole) and selective serotonin reuptake inhibitors (SSRIs; such as sertraline and paroxetine)
Increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use"). If this combination is necessary, careful clinical and laboratory monitoring (including blood clotting time) should be ensured.
Antidiabetic drugs (insulin, sulfonylurea-containing drugs)
Salicylates may enhance the hypoglycemic effect of antidiabetic drugs.
Digoxin and lithium
When used simultaneously with digoxin and lithium, their plasma concentrations increase due to reduced renal excretion. At the beginning and during the period of treatment with acetylsalicylic acid, it is recommended to monitor plasma concentrations of digoxin and lithium. Dosage adjustment may be required.
Barbiturates
The concentration of barbiturates in the blood serum may increase when used simultaneously with acetylsalicylic acid.
Aldosterone antagonists, loop diuretics
The effectiveness of aldosterone antagonists (e.g. spironolactone) and loop diuretics may be reduced when used simultaneously with acetylsalicylic acid.
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 deterioration of renal function in patients with pre-existing renal dysfunction (e.g. in dehydrated patients and in elderly patients). This may lead to the development of acute renal failure, which is usually reversible. It is recommended to use the combination of NSAIDs with ACE inhibitors/angiotensin II antagonists with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function should be considered at the beginning of combination therapy and at regular intervals during treatment.
Diuretics: risk of acute renal failure due to decreased glomerular filtration rate due to decreased renal prostaglandin synthesis. At the beginning of treatment, hydration of the patient and monitoring of renal function are recommended. In patients taking acetylsalicylic acid and these drugs concomitantly, it is recommended to carefully monitor blood pressure and adjust the dose if necessary.
Carbonic anhydrase inhibitors (acetazolamide)
May lead to serious cases of acidosis and increased neurotoxicity.
Corticosteroids for systemic use
The risk of ulcers and gastrointestinal bleeding may increase with the simultaneous use of acetylsalicylic acid and corticosteroids.
Methotrexate (at a dosage of <15 mg/week)
When used with methotrexate at doses less than 15 mg/week, 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). During the first weeks of treatment, blood tests should be performed weekly.
Patients with renal impairment, even mild, as well as elderly patients, require careful monitoring of their condition.
Other NSAIDs
Due to the mutually reinforcing effect, the risk of ulcers and gastrointestinal bleeding increases.
Ibuprofen
Concomitant use of acetylsalicylic acid with ibuprofen prevents irreversible inhibition of platelets by acetylsalicylic acid. Treatment of patients at risk of cardiovascular disease with ibuprofen may limit the cardioprotective effect of acetylsalicylic acid.
Metamizole
When used simultaneously 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 simultaneously.
Cyclosporine, tacrolimus
Concomitant use of NSAIDs and cyclosporine or tacrolimus may increase the nephrotoxic effect of the latter. Renal function should be monitored when this combination is used.
Sodium valproate/valproic acid
When used simultaneously with valproates, acetylsalicylic acid displaces them from their binding to plasma proteins, which leads to an increase in the concentration of valproates in the blood serum and an increase in their clinical and side effects.
Sulfonamides and triiodothyronine
Enhancement of the effects of sulfonamides and triiodothyronine.
Penicillin
Prolongation of the half-life of penicillin from blood plasma.
Phenytoin
Salicylates reduce the binding of phenytoin to plasma albumin. This may result in a decrease in total plasma phenytoin levels and an increase in the fraction of free phenytoin. The concentration of unbound phenytoin and, therefore, the therapeutic effect are not significantly altered.
Alcohol
Increased risk of gastrointestinal bleeding and prolongation of bleeding time due to the synergism of acetylsalicylic acid and alcohol.
Application features
Acetylsalicylic acid in dosages of 75 mg and 100 mg is not used as an analgesic-antipyretic and anti-inflammatory agent.
The risk of bleeding is particularly increased during or after surgery (including minor surgical interventions, such as tooth extraction) due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after the use of drugs containing acetylsalicylic acid. Therefore, caution should be exercised before surgery, including dental surgery. Temporary discontinuation of therapy may be necessary.
Acetylsalicylic acid is not recommended for use in case of menorrhagia, as it may lead to increased menstrual bleeding.
It should be used with caution in patients with hypertension and in patients with a history of gastric or duodenal ulcer or bleeding, or if they are undergoing anticoagulant therapy.
The drug should be used with caution in patients with digestive tract diseases, the presence of symptoms of chronic gastric or duodenal dyspepsia or their recurrence.
Patients should report any unusual bleeding to their doctor. In the event of gastrointestinal bleeding and ulcerogenic effects, treatment with the drug should be discontinued.
The drug should be used with caution in patients with moderate renal insufficiency (severe degree is a contraindication) or cardiovascular circulatory disorders (e.g. renal vascular pathology, congestive heart failure, hypovolemia, extensive surgery, sepsis or severe bleeding), since acetylsalicylic acid may also increase the risk of renal dysfunction and acute renal failure.
The drug should be used with caution in patients with moderate hepatic impairment (severe is a contraindication), liver disease. Patients with mild or moderate hepatic impairment should have regular liver function tests.
The drug should be used with caution in patients with bronchial asthma, nasal polyps or a general tendency to hypersensitivity, since acetylsalicylic acid may cause the development of bronchospasm or an attack of bronchial asthma or other hypersensitivity reactions. Risk factors include a history of asthma, hay fever, nasal polyps or chronic respiratory disease, allergic reactions (e.g. skin reactions, itching, urticaria) to other substances in history.
Serious skin reactions, including Stevens-Johnson syndrome, have been reported rarely in association with the use of acetylsalicylic acid (see section 4.8). At the first appearance of skin rash, mucosal lesions or other signs of hypersensitivity, treatment with acetylsalicylic acid should be discontinued.
The drug should be used with caution in patients with hypersensitivity to analgesics, anti-inflammatory, antirheumatic drugs, as well as allergies to other substances.
The drug should be used with caution in patients with severe 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.
Elderly patients are particularly susceptible to the development of adverse reactions to NSAIDs, including acetylsalicylic acid, in particular gastrointestinal bleeding and perforation, which can be fatal (see section "Method of administration and dosage"). If long-term therapy with acetylsalicylic acid is necessary, such patients should be regularly examined.
The concomitant use of acetylsalicylic acid with other medicinal products that alter haemostasis (e.g. anticoagulants such as warfarin, thrombolytics and antiplatelet agents, anti-inflammatory agents and selective serotonin reuptake inhibitors) is not recommended unless strictly indicated, as this combination may increase the risk of bleeding (see section 4.5). If the combination cannot be avoided, careful monitoring/examination of the patient for signs of bleeding is recommended.
Regular use of acetylsalicylic acid may worsen the prognosis of patients with cerebral hemorrhage. Therefore, patients at increased risk of cerebral hemorrhage, such as patients with high blood pressure, should be monitored when using acetylsalicylic acid. An increased risk of cerebral hemorrhage has also been found in patients with a tendency to nosebleeds when using acetylsalicylic acid.
If prolonged vomiting, loss of consciousness or abnormal behavior occurs during treatment with acetylsalicylic acid, acetylsalicylic acid should be discontinued.
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 types of interactions").
When using low doses of acetylsalicylic acid, uric acid excretion may decrease, which may lead to a gout attack in susceptible patients.
Acetylsalicylic acid, when used in high doses, may potentiate the effects of sulfonylureas and insulin, which may increase the risk of hypoglycemia (see section "Interaction with other medicinal products and other types of interactions").
The use of acetylsalicylic acid may impair fertility in women and is not recommended for women attempting to conceive. For women who have difficulty conceiving or who are undergoing investigation of infertility, discontinuation of acetylsalicylic acid should be considered.
Use during pregnancy or breastfeeding
Pregnancy
Salicylates should be used with caution during the first and second trimesters of pregnancy. Salicylates are contraindicated during the third trimester of pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Available epidemiological data indicate a risk of miscarriage and foetal malformations (cardiac malformations and gastroschisis) after the 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 exposure in early pregnancy (1-4 months) do not indicate any association with an increased risk of malformations.
During the first and second trimesters of pregnancy, acetylsalicylic acid-containing drugs should not be prescribed unless clearly necessary. For women who may be pregnant or for patients in the first and second trimesters of pregnancy, the dose of acetylsalicylic acid-containing drugs should be as low as possible and the duration of treatment should be as short as possible.
Cases of implantation disorders, embryotoxic and fetotoxic effects and effects on the child's learning ability have been reported after prenatal exposure to salicylates.
According to animal studies, the use of salicylates causes adverse reactions in the fetus (such as increased mortality, growth disorders, salicylate intoxication), but no controlled studies have been conducted in pregnant women.
According to previous experience, the risk is low when using the drug in therapeutic doses.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension) and/or renal dysfunction with possible further development of renal failure with oligohydramnios;
prolonged bleeding time, anti-aggregation effect that may occur in the woman and fetus at the end of pregnancy;
prolongation of bleeding time is also possible 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.
Breast-feeding
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
No research was conducted.
Method of administration and doses
For oral use.
The tablets should be swallowed whole with sufficient liquid (1/2 glass of water). The tablets should not be crushed, cut or chewed, as the enteric coating of the tablet prevents the drug from irritating the intestines.
To reduce the risk of death in patients with suspected acute myocardial infarction, the drug should be used at a dose of 75-300 mg per day. Continue to take a maintenance dose of 75-300 mg per day for 30 days after the infarction. After 30 days, the issue of further prevention of recurrent myocardial infarction should be considered.
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 had a myocardial infarction, use 75-300 mg per day.
For secondary prevention of stroke, use the drug at a dose of 75-300 mg per day.
To reduce the risk of disease development and death in patients with stable and unstable angina, use 75-300 mg per day.
For the prevention of thromboembolism after vascular surgery (percutaneous transluminal catheter angioplasty (PTCA), carotid endarterectomy, coronary artery bypass grafting (CABG), arteriovenous bypass grafting), use the drug at a dose of 75-150 mg per day every day or 300 mg per day every other day.
For the prevention of deep vein thrombosis and pulmonary embolism after long-term immobilization (after surgery) - 75-150 mg per day or 300 mg per day every other day.
To reduce the risk of myocardial infarction in patients with a high risk of developing cardiovascular complications (diabetes mellitus, controlled arterial hypertension) and patients with a multifactorial risk of cardiovascular disease (hyperlipidemia, obesity, smoking, old age), use 75 mg per day or 300 mg per day every other day.
Elderly patients
In general, elderly patients are more prone to the development of adverse reactions, therefore acetylsalicylic acid should be used with caution in this category of patients. In the absence of severe renal or hepatic insufficiency, the drug is used in the usual doses recommended for adults. Treatment should be reviewed regularly (see section "Special instructions").
Children.
The medicine is not intended for use in children.
The use of acetylsalicylic acid in children under 16 years of age may cause severe side effects (see section "Special warnings and precautions for use").
Overdose
Symptoms of severe poisoning may develop 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.
Chronic salicylate poisoning can be latent because its symptoms are nonspecific. Moderate chronic intoxication is usually observed only after repeated ingestion of large doses.
Acute intoxication is indicated by a pronounced change in the acid-base balance, which may vary depending on the age of the patient and the severity of intoxication. Its most common manifestation in children is metabolic acidosis. The severity of the condition cannot be assessed solely on the basis of the concentration of salicylates in the blood plasma. 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.
Reservation.
Local signs of irritation that usually dominate in ASA overdose, such as nausea, vomiting, and stomach pain, may be absent because this dosage form of ASA has an enteric coating and resorption occurs only in the small intestine.
Symptoms.
Headache, nausea, hypocalcemia, hypokalemia, hyper-/hypoglycemia, skin rash, dizziness, gastrointestinal bleeding, inhibition of thromboembolism to coagulopathy, cardiovascular disorders (from arrhythmia, arterial hypotension to cardiac arrest), tinnitus, visual and hearing impairment, tremor, confusion, hyperthermia, increased sweating, hyperventilation, acid-base and electrolyte imbalance, dehydration, convulsions, rhabdomyolysis, pulmonary edema, coma and respiratory failure.
Tinnitus is possible at plasma salicylate concentrations above 150-300 μg/ml. More serious adverse reactions are observed at plasma salicylate concentrations above 300 μg/ml.
Therapy.
There is no specific antidote. Due to life-threatening conditions due to severe intoxication, all necessary precautions should be taken immediately: prevention or reduction of resorption, gastric lavage in the early stages (up to one hour after ingestion), activated charcoal, control and appropriate correction of electrolytes, water balance, correction of thermoregulation, support of breathing. Use of glucose. Sodium bicarbonate to correct acidosis and to accelerate excretion (urine pH >8). Glycine: initial dose - 8 g orally, then - 4 g every 2 hours for 16 hours. Hemoperfusion or hemodialysis is possible (the need for use can be established in the poison control center).
Side effects
Blood and lymphatic system disorders:
prolonged bleeding time;
Rare: thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia.
On the part of the immune system:
uncommon: asthma;
rare: hypersensitivity reactions such as erythematous/eczematous skin reactions, urticaria, rhinitis, nasal congestion, bronchospasm, angioedema, allergic edema, anaphylactic reactions, drop in blood pressure to the point of shock;
very rare: severe skin reactions, including exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Metabolism and nutrition:
rare: hypoglycemia, iron deficiency anemia, acid-base imbalance; frequency unknown: hyperuricemia.
From the nervous system:
rare: headache, dizziness, vertigo, tinnitus, visual impairment, hearing impairment, confusion.
From the vascular system:
Respiratory, thoracic and mediastinal disorders:
uncommon: rhinitis, dyspnea.
From the reproductive system and mammary glands:
rare: menorrhagia.
Skin and subcutaneous tissue disorders:
rare: purpura, erythema nodosum.
From the gastrointestinal tract:
frequent: microbleeds (70%), gastric symptoms, abdominal pain, heartburn;
uncommon: dyspepsia, nausea, vomiting, diarrhea;
rare: gastrointestinal bleeding, gastrointestinal ulcers, which in very rare cases may lead to perforation, with corresponding clinical symptoms and changes in laboratory parameters.
Hepatobiliary disorders:
rare: hepatic dysfunction (e.g. increased transaminase levels); frequency unknown: hepatic failure.
From the kidneys and urinary tract:
Renal dysfunction and acute renal failure have been reported.
Others:
rare: Reye's syndrome (see section "Special warnings and precautions for use").
Spontaneous reports included information on other adverse reactions for all dosage forms of ASA, including during oral short-term and long-term therapy, therefore it is not possible to assign a frequency category according to CIOMS III.
Hemolysis and hemolytic anemia have been observed in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Due to its antiplatelet 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. Symptoms may persist for 4-8 days after discontinuation of acetylsalicylic acid.
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.
Hemorrhages can lead to acute and chronic posthemorrhagic anemia/iron deficiency anemia (due to so-called occult microbleeding) with corresponding laboratory manifestations and clinical symptoms, such as asthenia, pallor of the skin, hypoperfusion.
Gastrointestinal disorders, such as general signs and symptoms of dyspepsia, epigastric pain and abdominal pain; in isolated cases - gastrointestinal inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which can potentially cause gastrointestinal hemorrhage and perforation in isolated cases with corresponding laboratory parameters and clinical manifestations.
Hypersensitivity reactions with associated laboratory and clinical manifestations include asthmatic status, mild to moderate skin reactions, as well as respiratory, gastrointestinal and cardiovascular reactions, including symptoms such as rash, oedema, pruritus, cardiorespiratory failure and very rarely severe reactions including anaphylactic shock.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
Balkanpharma-Dupnitsa JSC/ Balkanpharma-Dupnitsa AD.
Location of the manufacturer and address of its place of business.
Street
