Diavenon hard capsules 5mg/75mg №10×3

Product Description Diavenon. Release formCapsules. INNBisoprolol + acetylsalicylic acid. FTGHypotensive combined agent. Brief description of the finished dosage form White opaque capsules, size 1, labeled 5/75. Composition of the medicinal product One capsule contains: active substances: bisoprolol fumarate 5 mg, acetylsalicylic acid 75 mg; excipients: corn starch, microcrystalline cellulose, stearic acid, magnesium stearate, polyvinyl alcohol, partially hydrolyzed, titanium dioxide (E171), talc, lecithin, xanthan gum, gelatin. Pharmacotherapeutic groupPharmacotherapeutic group: beta-blockers; beta-blockers, other combinations. ATX code: C07FX04 Pharmacological properties Pharmacodynamics Bisoprolol is a powerful, highly selective beta-1-adrenergic blocker. The mechanism of action of bisoprolol in hypertension is not fully understood, but it is known that the drug significantly reduces the activity of renin in blood plasma. In patients with angina pectoris, blockade of beta-1-adrenergic receptors leads to a decrease in the strength and frequency of heart contractions and thus leads to a decrease in myocardial oxygen demand. As a result, bisoprolol is able to effectively eliminate or reduce the symptoms of angina pectoris. Acetylsalicylic acid inhibits the process of platelet activation: by blocking platelet cyclooxygenase by its acetylation, it inhibits the synthesis of thromboxane A2, a physiologically active substance that is secreted by platelets and plays an important role in the occurrence of complications of atherosclerotic diseases. With repeated administration of acetylsalicylic acid in doses of 20-325 mg, the activity of the enzyme is reduced by 30-95%. Due to the fact that the relationship of acetylsalicylic acid with this enzyme is irreversible, the effect of the drug persists throughout the life of the platelet (7-10 days). The inhibitory effect of acetylsalicylic acid does not weaken with long-term treatment. After discontinuation of treatment, enzyme activity gradually increases as the platelet population is restored (24-48 hours after discontinuation). Acetylsalicylic acid prolongs bleeding time by approximately 50-100%, but this value may vary in different patients. Pharmacokinetics Bisoprolol After oral administration, bisoprolol is absorbed. The bioavailability of bisoprolol when administered orally is about 90%, and the degree of binding to plasma proteins is about 30%. The volume of distribution is 3.5 liters. The total clearance is approximately 15 l / h. The half-life of bisoprolol from blood plasma is 10-12 hours, which provides a 24-hour therapeutic effect when taking bisoprolol with a frequency of once a day. Bisoprolol is excreted from the body in two ways. About 50% of the administered dose is metabolized by the liver to form inactive metabolites, which are then excreted by the kidneys. The remaining 50% of the administered dose is excreted by the kidneys unchanged. Since bisoprolol is excreted from the body equally by the kidneys and liver, dose adjustment of bisoprolol in patients with impaired liver function or renal insufficiency is not required. The pharmacokinetics of bisoprolol in patients with stable chronic heart failure and impaired liver or kidney function has not been studied. The pharmacokinetics of bisoprolol is linear and does not depend on age. In patients with chronic heart failure class III according to the classification of the New York Heart Association (NYHA), the concentration of bisoprolol in blood plasma was higher, and its half-life was longer than in healthy volunteers. The maximum concentration of bisoprolol in blood plasma in the equilibrium state when it was administered at a daily dose of 10 mg was 64 ± 21 ng / ml, and the half-life was 17 ± 5 hours. Acetylsalicylic acid Absorption The maximum plasma concentration (Cmax) is reached after approximately 50 minutes (tmax). The main site of absorption is the proximal small intestine. However, during absorption, a significant part of the administered dose of acetylsalicylic acid undergoes hydrolysis to salicylic acid in the intestinal wall. The degree of hydrolysis depends on the rate of absorption. Simultaneous ingestion of food leads to a slowdown in the absorption of acetylsalicylic acid (to a decrease in plasma concentration), but does not reduce the degree of absorption. Distribution The volume of distribution of acetylsalicylic acid is approximately 0.16 ml per 1 kg of body weight. The first substance formed from acetylsalicylic acid in the body is salicylic acid, the degree of binding of which to blood plasma proteins (mainly albumin) exceeds 90%. Salicylic acid is able to slowly diffuse into the synovial fluid, pass through the placental barrier and penetrate into breast milk. Biotransformation Acetylsalicylic acid is predominantly hydrolyzed to form salicylic acid. The half-life of acetylsalicylic acid is quite short and is approximately 15-20 minutes. Salicylic acid is subsequently metabolized, forming conjugates with glycine and glucuronic acid. During metabolism, trace amounts of gentisic acid are also formed. With the introduction of high therapeutic doses of acetylsalicylic acid, the activity of the enzymatic conversion of salicylic acid in the body becomes insufficient, as a result of which its pharmacokinetics becomes non-linear. This leads to an extension of the apparent half-life of salicylic acid from several hours to about 24 hours. Withdrawal Acetylsalicylic acid is excreted mainly by the kidneys. The tubular reabsorption of acetylsalicylic acid is pH dependent. With alkalization of urine, the proportion of unchanged acetylsalicylic acid in the urine can increase from approximately 10 to 80%. Indications for use Diavenon is indicated: for the treatment of arterial hypertension after its stabilization, achieved earlier as a result of treatment with the active substances of this drug (in the form of independent drugs); for the treatment of angina pectoris after its stabilization, previously achieved as a result of treatment with the active substances of this medicinal product (in the form of independent medicinal products). Contraindications The use of the medicinal product is contraindicated in patients with the following diseases: Hypersensitivity to the active substances or to any of the excipients of the medicinal product. Hypersensitivity to salicylic acid derivatives or prostaglandin synthetase inhibitors (in some patients with bronchial asthma, taking the drug may provoke an attack or lead to fainting). Acute heart failure or decompensated chronic heart failure requiring treatment with inotropic agents. Cardiogenic shock. Sinoatrial blockade. Sick sinus syndrome. Atrioventricular block II or III degree (in the absence of an artificial pacemaker). Bradycardia with clinical symptoms. Arterial hypotension with clinical symptoms. Severe bronchial asthma or severe chronic obstructive pulmonary disease (COPD). Severe clinical forms of obliterating diseases of peripheral arteries and Raynaud’s syndrome. Pheochromocytoma without appropriate treatment (see section “Precautions for use”). metabolic acidosis. Symptoms of stomach problems or information about the occurrence of pain in the stomach with this drug in the past. Active peptic ulcer and / or bleeding from the stomach or intestines (see section “Precautions for use”). Hemorrhagic stroke in history. Severe liver or kidney failure. Hemorrhagic diathesis or bleeding disorders, in particular, hemophilia or hypoprothrombinemia. Deficiency of glucose-6-phosphate dehydrogenase. Simultaneous use of methotrexate in doses> 15 mg per week. Allergy to peanuts or soy. Precautions for use It is necessary to consult a doctor even if the following warnings apply to situations observed in the past. Bisoprolol Bisoprolol should be used with caution in the following situations: Presence of diabetes mellitus with significant fluctuations in blood glucose levels; the use of the drug may mask the symptoms of hypoglycemia (in particular, tachycardia, palpitations and sweating). Strict diet. Simultaneous desensitizing therapy. Like other beta-blockers, bisoprolol can increase sensitivity to allergens and exacerbate the severity of anaphylactic reactions. Adrenaline treatment may not be effective enough. Atrioventricular block I degree. Prinzmetal’s angina. Obliterating diseases of peripheral arteries. There may be an increase in symptoms, especially after the start of treatment. Bisoprolol should be used with caution in patients with hypertension or angina pectoris and concomitant heart failure. The use of beta-blockers (in particular, bisoprolol) in patients with psoriasis or the presence of this disease in the past is possible only after a thorough assessment of the balance of benefits and risks associated with treatment. Treatment with bisoprolol may mask the symptoms of thyrotoxicosis. There is no experience with the use of bisoprolol in patients with CHF in combination with the following diseases and conditions: insulin-dependent diabetes mellitus (type I); restrictive cardiomyopathy; congenital heart defects; hemodynamically significant organic damage to the heart valves; myocardial infarction within the last 3 months. The use of bisoprolol in patients with pheochromocytoma is allowed only after reaching the blockade of alpha-adrenergic receptors. In patients under anesthesia, blockade of beta-adrenergic receptors helps to reduce the frequency of arrhythmias and myocardial ischemia during anesthesia and intubation, as well as in the postoperative period. In accordance with current recommendations, maintenance therapy with beta-blockers should be continued during the perioperative period. The anesthesiologist should be aware of the patient’s treatment with a beta-blocker, since the drug used may interact with other drugs, resulting in the occurrence of bradyarrhythmias, a weakening of reflex tachycardia, and a decrease in reflex compensatory reactions in response to blood loss. If the use of a beta-blocker must be stopped before surgery, the dose of the drug should be gradually reduced and treatment should be completed approximately 48 hours before the patient is put into anesthesia. In patients with bronchial asthma or other chronic obstructive pulmonary diseases with the possibility of clinical symptoms, it is recommended to simultaneously carry out bronchodilator therapy. In patients with bronchial asthma, in some cases, airway resistance may increase, which may require an increase in doses of beta-2-agonists. The simultaneous use of bisoprolol with calcium antagonists from the group of verapamil or diltiazem or with centrally acting antihypertensive drugs is usually not recommended (see section “Interactions with other drugs and other types of interactions”). Athletes. Athletes should be aware that bisoprolol, which is part of this drug, can cause positive results in doping tests. Acetylsalicylic acid The simultaneous use of acetylsalicylic acid with anticoagulants (coumarin derivatives, heparin) is not recommended and in most cases should be avoided. If concomitant use is essential, international normalized ratio (INR) should be monitored frequently during treatment and the patient should be educated to recognize symptoms of bleeding (especially from the gastrointestinal tract). Patients with bronchial asthma and allergic rhinitis (acetylsalicylic acid can cause severe urticaria, angioedema or bronchospasm) should also be under careful clinical supervision. The use of acetylsalicylic acid in patients with a history of peptic ulcer and/or gastrointestinal bleeding is not recommended as it may cause irritation and bleeding of the gastric mucosa. If the patient experiences objective and subjective symptoms of bleeding associated with exposure to acetylsalicylic acid, its use should be discontinued. Greater caution should be exercised in the treatment of patients with impaired liver and kidney function. The simultaneous use of this active substance with uricosuric agents such as benzbromarone, probenecid and sulfinpyrazone is not recommended (see section “Interactions with other drugs”). An overdose of acetylsalicylic acid is especially dangerous in elderly patients. Acetylsalicylic acid should be used with caution in excessively heavy menstrual bleeding. It is recommended to stop taking acetylsalicylic acid before surgical interventions (including extraction of teeth) due to the risk of increasing the duration and intensity of bleeding. The duration of the break in treatment is set individually in each case, but in most cases it is one week. Fertility The use of acetylsalicylic acid may reduce the chance of pregnancy due to a negative effect on ovulation. This effect is reversible after discontinuation of acetylsalicylic acid. In this regard, drugs containing acetylsalicylic acid should not be taken by women who are planning a pregnancy. Women who have difficulty conceiving or are undergoing fertility testing should consider discontinuing acetylsalicylic acid. Use during pregnancy and lactation If the patient is pregnant, breastfeeding, suspects that she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using the medicinal product. Diavenon should not be used during pregnancy unless absolutely necessary. There are no data on the use of Diavenon in pregnant women. Bisoprolol has pharmacological effects that may adversely affect pregnancy and / or the fetus / newborn. One of the effects of beta-blockers is a decrease in placental perfusion, which can lead to growth retardation or fetal death, miscarriage, or preterm birth. The drug may cause undesirable effects in the body of the fetus or newborn (in particular, hypoglycemia and bradycardia). If treatment with a beta-blocker is necessary, a drug from the group of selective beta-1-adrenoceptor blockers should be preferred. If there are absolute indications for the use of bisoprolol, during treatment it is necessary to monitor the state of the uteroplacental circulation and fetal growth. If adverse effects on pregnancy or the fetus are identified, alternative treatment should be considered. A newborn baby should be closely monitored. Symptoms of hypoglycemia and bradycardia usually appear within the first 3 days. The effects of acetylsalicylic acid include suppression of labor, premature (intrauterine) closure of the ductus arteriosus, pulmonary hypertension in the newborn, tricuspid valve insufficiency, kidney damage with possible renal failure, oligohydramnios, and blood clots. Breastfeeding There is no evidence whether bisoprolol is excreted in human breast milk. Salicylates and their metabolites pass into human breast milk in small amounts. In this regard, breast-feeding during treatment with this drug is not recommended. Influence on the ability to drive vehicles and maintain mechanisms Studies of the effect of the drug on the ability to drive vehicles and moving mechanisms have not been conducted. In a study in patients with coronary heart disease, bisoprolol did not affect the ability to drive vehicles, however, individual reactions to treatment with this drug are possible, which may impair the ability to drive and control moving mechanisms. This possibility is especially important to take into account at the initial stages of treatment, when changing the dosage of the drug or in the case of alcohol consumption. If you experience dizziness or fatigue while taking Diavenon, you should refrain from driving vehicles and servicing potentially dangerous mechanisms until these symptoms completely stop. Information about excipients that are important for the safe and effective use of the medicinal product This medicinal product contains soy lecithin and is therefore contraindicated in patients with peanut or soy allergy. Interaction with other medicinal products and other forms of interaction It is necessary to inform the doctor or pharmacist about all drugs currently or recently used, as well as the drugs that the patient plans to use. Studies of the interaction of Diavenon with other drugs have not been conducted. Bisoprolol Drugs, the simultaneous use of which is not recommended: Calcium antagonists of the verapamil group and, to a lesser extent, the diltiazem group: inhibition of myocardial contractility and atrioventricular conduction is possible. Intravenous administration of verapamil to a patient receiving treatment with a beta-blocker can lead to severe arterial hypotension and atrioventricular blockade. Centrally acting antihypertensive drugs (in particular, clonidine, methyldopa, moxonidine, rilmenidine): the simultaneous use of these drugs can cause an additional decrease in the tone of the central sympathetic nervous system, which in turn leads to a decrease in heart rate and cardiac output, as well as vasodilation. Abrupt discontinuation of treatment with these drugs (especially before discontinuation of a beta-blocker) may increase the risk of “rebound” hypertension. Drugs, the simultaneous use of which requires increased caution: Class I antiarrhythmic drugs (in particular, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone): there may be a slowdown in atrioventricular conduction and an increase in the negative inotropic effect. Calcium antagonists from the group of dihydropyridine derivatives (in particular, felodipine and amlodipine): simultaneous use may increase the risk of arterial hypotension, and possibly also increase the risk of an additional decrease in the pumping function of the ventricles of the heart in patients with heart failure. Antiarrhythmic drugs of class III (in particular, amiodarone): potentiation of the effect in relation to atrioventricular conduction may be observed. Parasympathomimetics: simultaneous use may lead to a slowdown in atrioventricular conduction and an increased risk of bradycardia. Topical beta-blockers (particularly in the form of eye drops for the treatment of glaucoma) may enhance the systemic effects of bisoprolol. Insulin and oral hypoglycemic agents: there may be an increase in hypoglycemic effect. Blockade of beta-adrenergic receptors may mask the symptoms of hypoglycemia. Anesthetics: weakening of reflex tachycardia and increased risk of arterial hypotension (see also section “Precautions for use”). Cardiac glycosides (in particular, digoxin): decrease in heart rate, slowing atrioventricular conduction. Non-steroidal anti-inflammatory drugs (NSAIDs) can weaken the hypotensive effect of bisoprolol. Beta-agonists (in particular, isoprenaline, dobutamine): when used simultaneously with bisoprolol, a weakening of the effects of both drugs may be observed. Sympathomimetics that stimulate beta- and alpha-adrenergic receptors (in particular, norepinephrine, adrenaline): when used simultaneously with bisoprolol, there may be a manifestation of vasoconstrictive effects of sympathomimetics associated with effects on alpha-adrenergic receptors, such as increased blood pressure and increased intermittent claudication. This interaction is more likely with the use of non-selective beta-blockers. The simultaneous use of antihypertensive drugs or other drugs with hypotensive potential (for example, tricyclic antidepressants, barbiturates, phenothiazine derivatives) may increase the risk of arterial hypotension. Medicinal products, the simultaneous use of which must be carefully weighed: Mefloquine: increased risk of bradycardia. Monoamine oxidase inhibitors (with the exception of MAO type B inhibitors): increased hypotensive effect of beta-blocker and increased risk of hypertensive crisis. Rifampicin: a slight decrease in the half-life of bisoprolol (possibly as a result of activation of liver enzymes that metabolize drugs). Dose adjustment is usually not required. Ergot alkaloid derivatives: exacerbation of peripheral circulatory disorders. Acetylsalicylic acid Treatment with multiple inhibitors of platelet aggregation such as acetylsalicylic acid, other NSAIDs, ticlopidine, clopidogrel, tirofiban, and eptifibatide, or in combination with heparin and its derivatives (eg, hirudin or fondaparinux), oral anticoagulants, and thrombolytics leads to an increased risk of bleeding. In such situations, it is necessary to regularly monitor the clinical and biological indicators of hemostasis. Medicinal products, the simultaneous use of which is contraindicated: Methotrexate (at doses> 15 mg per week): with the simultaneous use of methotrexate and acetylsalicylic acid, an increase in hematological toxicity of methotrexate is observed as a result of slowing its renal clearance under the influence of acetylsalicylic acid. In this regard, the simultaneous use of this drug with methotrexate is contraindicated (see section “Contraindications”). Drugs, the simultaneous use of which is not recommended: Uricosuric agents (benzbromarone, probenecid and sulfinpyrazone): slowing down the excretion of uric acid due to competitive inhibition of its elimination through the renal tubules. In this regard, the simultaneous use of this drug with uricosuric agents is not recommended (see section “Precautions for use”). Medicinal products that require precautionary measures when used simultaneously: Diuretics: Risk of acute renal failure due to reduced renal prostaglandin synthesis and subsequent reduction in glomerular filtration rate. At the beginning of treatment, it is necessary to saturate the patient’s body with fluid and assess the state of kidney function. Glucocorticoids: the simultaneous use of drugs in this group may increase the risk of bleeding and ulceration in the gastrointestinal tract. Methotrexate (at doses <15 mg per week): with the simultaneous use of methotrexate and acetylsalicylic acid, an increase in hematological toxicity of methotrexate is observed as a result of slowing its renal clearance under the influence of acetylsalicylic acid. In the first weeks of combined treatment with these drugs, it is necessary to determine the parameters of the general blood test weekly. Patients with impaired renal function (even mild), as well as elderly patients need enhanced monitoring. Heparin (in therapeutic doses or in elderly patients): when used simultaneously with acetylsalicylic acid, there is an increased risk of bleeding. In the case of simultaneous use of both drugs, careful monitoring of INR, activated partial thromboplastin time (APTT) and / or bleeding time is required. Cardiac glycosides (particularly digoxin): NSAIDs (including acetylsalicylic acid) may exacerbate heart failure, decrease glomerular filtration rate (GFR), and increase plasma concentrations of cardiac glycosides. Lithium medicines: slowing down the excretion of lithium from the body. Drugs / substances, the simultaneous use of which must be carefully weighed: Other anticoagulants (coumarin derivatives, heparin in prophylactic doses), antiplatelet drugs and thrombolytics: increased risk of bleeding. Other NSAIDs: increased risk of bleeding and damage to the gastrointestinal mucosa, as well as an additional prolongation of bleeding time. Antacids: possible stimulation of renal excretion of acetylsalicylic acid as a result of alkalinization of urine. Alcohol: additional damaging effect on the mucosa of the gastrointestinal tract and prolongation of bleeding time. Dosing and Administration Diavenon should always be used in accordance with the doctor's recommendations. In case of doubt, a doctor should be consulted. Adults The usual adult dose is 1 capsule per day. Children Diavenon is not intended for use in children. Elderly patients Usually dose adjustment is not required. Patients with severe renal or hepatic impairment Due to the fact that Diavenon contains acetylsalicylic acid, it is contraindicated in patients with severe hepatic or renal impairment. The use of the drug in patients with mild or moderate hepatic or renal insufficiency requires increased caution. Directions for use Capsules should be swallowed whole with water. The drug should be taken at the same time. Duration of treatment Treatment is usually continued for a long time and should not be stopped abruptly, as this may lead to a temporary worsening of the condition. The warning against abrupt discontinuation of treatment is particularly relevant in patients with ischemic heart disease. Reduce the daily dose of the drug should be gradual. In case of missing a dose of the drug Diavenon If the patient has forgotten to take Diavenon, it should be taken as soon as possible if no more than 12 hours have passed since the missed dose. If more than 12 hours have passed since the missed dose, you should wait for the next dose of the drug. Do not take a double dose of the drug to make up for the missed dose. If during treatment it seems to the patient that the effect of the drug is too strong or weak, he should consult a doctor. Overdose In case of taking Diavenon in a dose greater than prescribed, you should immediately consult a doctor. Possible symptoms of an overdose of bisoprolol: bradycardia, arterial hypotension, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol is characterized by pronounced interindividual variability. Particularly high sensitivity is observed in patients with heart failure. In case of overdose, treatment with bisoprolol should be discontinued. The patient is shown supportive and symptomatic therapy. There is little evidence that bisoprolol is practically not excreted from the body during dialysis. Due to the low content of acetylsalicylic acid in this drug, its overdose is unlikely. However, intoxication in young children (accidental overdose) and overdose in the treatment of elderly patients may be manifested by the following symptoms: dizziness, headache, tinnitus, confusion and gastrointestinal disorders (nausea, vomiting and pain in the stomach) . With severe intoxication, serious violations of the acid-base balance in the body occur. Symptoms such as pyrexia and sweating leading to dehydration, restlessness, seizures, hallucinations and hypoglycemia may be observed. Depression of the nervous system can lead to coma, cardiovascular collapse, and respiratory arrest. In the case of taking acetylsalicylic acid in a toxic dose, the patient must be hospitalized. With moderate intoxication, it is necessary to try to induce vomiting. If this fails, gastric lavage should be performed. After that, activated charcoal (adsorbent) and sodium sulfate (laxative) are applied. In severe intoxication, hemodialysis is the preferred treatment. To eliminate other manifestations of intoxication, symptomatic treatment is prescribed. Side effects Like all medicines, Diavenon can have side effects, although not everyone gets them. Summary table of side effects Undesirable reactions are classified depending on the frequency of occurrence and belonging to a particular class of organ systems. According to the frequency of occurrence, side effects were divided into the following categories of occurrence: very often (≥ 1/10), often (from ≥ 1/100 to < 1/10), infrequently (from ≥ 1/1000 to < 1/100), rarely (from ≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency unknown (cannot be estimated from the available data). Bisoprolol Below are data on side effects in the treatment of bisoprolol. Psychiatric disorders Uncommon: sleep disturbances, depression. Rarely: nightmares, hallucinations. Nervous system disorders: Common: dizziness*, headache*. Rarely: fainting. On the part of the organ of vision: Rare: decreased production of tears (must be taken into account if the patient wears contact lenses). Very rare: conjunctivitis. Hearing disorders and labyrinth disorders: Rare: hearing impairment. Cardiac disorders: Uncommon: bradycardia, exacerbation of existing heart failure, atrioventricular conduction disturbances. Vascular disorders: Often: a feeling of coldness or numbness of the extremities. Infrequently: arterial hypotension. Respiratory, thoracic and mediastinal disorders: Uncommon: Bronchospasm in patients with asthma or a history of obstructive airways disease. Rare: allergic rhinitis. Gastrointestinal disorders: Common: Gastrointestinal disorders such as nausea, vomiting, diarrhea, constipation. Liver and biliary tract disorders: Rare: hepatitis. Skin and subcutaneous tissue disorders: Rare: hypersensitivity reactions (itching, redness, rash). Very rarely: the primary occurrence of psoriasis or aggravation of its course, the appearance of a psoriasis-like rash or alopecia (under the influence of beta-blockers). Musculoskeletal and connective tissue disorders: Uncommon: muscle weakness, muscle spasm. Genital and breast disorders: Rare: potency disorders. General disorders and disorders at the injection site: Often: fatigue*. Uncommon: asthenia. Influence on the results of laboratory and instrumental studies: Rarely: increased levels of triglycerides, increased levels of liver enzymes (ALT, ACT). *These symptoms are especially common after the start of treatment. In most cases, they are mild and disappear within 1-2 weeks. Acetylsalicylic acid Undesirable effects of acetylsalicylic acid are often dose-dependent and associated with its pharmacological action. Most side effects are disorders of the gastrointestinal tract. Patients with established allergies or asthma have an increased risk of hypersensitivity reactions. Cross-sensitivity to other NSAIDs may develop. Hemolysis and hemolytic anemia have also been reported in patients with severe glucose-6-phosphate dehydrogenase deficiency. Blood and lymphatic system disorders: Common: prolongation of bleeding time. This effect may persist for several days after discontinuation of treatment and may increase the risk of bleeding in the event of surgery or lead to increased blood loss during menstruation. Uncommon: intracranial hemorrhage, hematuria. Rarely: hemorrhagic syndrome (bleeding from the nose or gums, the presence of blood impurities in vomit and feces, etc.). Immune system disorders: Uncommon: urticaria, skin rash, angioedema, rhinitis, bronchospasm. Very rare: anaphylactic shock, increased symptoms of food allergies. Endocrine system disorders: Very rare: hypoglycemia. Metabolic and nutritional disorders: Very rare: slowing down the excretion of uric acid with the possible development of acute gout in patients predisposed to this disease (when treated with low doses of acetylsalicylic acid). Nervous system disorders: Rare: dizziness, headache, tinnitus. These symptoms are usually the first manifestations of an overdose (see section "Overdose"). Gastrointestinal disorders: Very common: gastric complaints indicating hyperacidity, nausea. Often: vomiting, gastritis, small or moderate blood loss through the gastrointestinal tract, diarrhea. With prolonged or repeated treatment, the described blood loss can lead to anemia. Infrequently: gastric bleeding, peptic ulcer of the stomach. Very rare: perforation of the gastrointestinal tract. Liver and biliary tract disorders: Very rare: Liver dysfunction. Skin and subcutaneous tissue disorders: Very rare: severe skin reactions (in particular, erythema multiforme exudative). Renal and urinary disorders: Very rare: acute renal failure, especially in patients with pre-existing impaired renal function, decompensated heart failure, nephrotic syndrome, or in patients receiving concurrent treatment with diuretics. Reporting Suspected Side Effects Reporting suspected side effects after drug registration is important. This allows continuous monitoring of the ratio.