Coplavix, 100 pcs., 100 mg+75 mg, film-coated tablets

Coplavix

The following are clinically significant adverse effects observed in five large clinical studies and post-marketing use of the combination of clopidogrel + ASA, clopidogrel as monotherapy and ASA as monotherapy.

The incidence of side effects was determined according to the WHO classification: very often (≥10%), often (≥1% and

Legend

1 Adverse effects that were observed when using a combination of clopidogrel and ASA.

2 Adverse effects that were observed with the use of clopidogrel.

3 Adverse effects that were observed with the use of ASA.

Hematological disorders (purpura/bruising; nosebleeds; hematuria; hemorrhages in skin tissue, bones and muscles; hematomas; hemorrhages in the joint cavity [hemarthrosis], in the conjunctiva, in the internal media and retina of the eye; bleeding from the respiratory tract, hemoptysis; bleeding from a surgical wound; intracranial hemorrhages (hemorrhagic strokes); bleeding from the gastrointestinal tract, retroperitoneal hemorrhages, etc.)

Bleeding and hemorrhage were the most frequently observed adverse events in clinical studies and post-marketing use of the drug, mainly occurring during the first month of treatment.

Often - major bleeding1: life-threatening bleeding requiring transfusion of 4 or more units of blood; other major bleeding requiring 2-3 units of blood transfusion; non-life-threatening major bleeding (in the COMMIT study, the incidence of major non-cerebral bleeding and intracranial hemorrhage was “infrequent”)1; minor bleeding (according to the ACTIVE-A study, the incidence of minor bleeding was “very common”)1; bleeding at the site of vascular puncture1,2; bruising2; hematomas2.

The incidence of major bleeding when using the combination of clopidogrel + ASA depended on the dose of ASA, as well as their frequency when using ASA alone.

Patients who stopped treatment more than 5 days before coronary artery bypass grafting did not experience an increase in major bleeding within 7 days after this procedure. In patients who remained on antiplatelet therapy in the last 5 days before coronary artery bypass surgery, the incidence of these bleedings after surgery was 9.6% (clopidogrel + ASA) and 6.3% (ASA alone).

Uncommon - fatal bleeding1: life-threatening bleeding: bleeding with a decrease in blood hemoglobin by more than 5 g/dl (according to the CLARITY clinical trial, the frequency of their development was “common”)1; bleeding requiring surgery1; intracranial hemorrhages (hemorrhagic strokes) (according to the CLARITY clinical trial, the incidence of their development was “common”)1; bleeding requiring the administration of inotropic drugs1; severe bleeding: purpura and nosebleeds were most often observed; Hematuria and intraocular hemorrhages, mainly conjunctival, were less common2.

Rarely - intraocular hemorrhages with significant visual impairment1, retroperitoneal hemorrhages1.

Unknown frequency (post-marketing experience) - serious cases of bleeding2, mainly hemorrhage in the skin tissue2, in the bones, muscles and joint cavity (hemarthrosis)2, in the eye tissue (conjunctival, in the internal media and retina of the eye)2, bleeding from respiratory tract2, hemoptysis2, nosebleeds2, hematuria2, bleeding from the surgical wound2; intracranial hemorrhage3, including fatal cases3, especially in elderly patients; other cases of fatal bleeding (in particular, bleeding from the gastrointestinal tract and retroperitoneal hemorrhage)2.

From the hematopoietic system: infrequently - a decrease in the number of platelets in the peripheral blood1, severe thrombocytopenia with a platelet count in the peripheral blood of 80,000/μl, but >30,000/μl1, leukopenia1, a decrease in the number of neutrophils in the peripheral blood1, eosinophilia1, prolongation of bleeding time1; rarely - neutropenia1, including severe neutropenia (

From the central and peripheral system: infrequently - headache1, dizziness1 and paresthesia1; rarely - vertigo1; unknown frequency (post-marketing experience of use) - change in taste sensations2.

From the digestive system: often - gastrointestinal bleeding1, dyspepsia1, abdominal pain1, diarrhea1; uncommon - nausea1, gastritis1, flatulence1, constipation1, vomiting1, gastric ulcer1 and duodenal ulcer1; unknown frequency (post-marketing experience) - colitis (including ulcerative or lymphocytic colitis)2, pancreatitis2, stomatitis2, esophagitis3, ulceration, esophageal perforation3, erosive gastritis3, erosive duodenitis3, ulcer or ulcerative perforation of the stomach and/or duodenum3, symptoms of upper tract lesions gastrointestinal tract, such as gastralgia3, ulcers of the small intestine (jejunum and ileum)3 and large intestine (colon and rectum)3, colitis and intestinal perforation3 (these reactions may or may not be accompanied by bleeding, and can occur with any dose of ASA, as well as in patients with and without warning symptoms and a history of serious gastrointestinal complications).

From the liver and biliary tract: unknown frequency (post-marketing experience of use) - hepatitis (infectious etiology)2, acute liver failure2, increased activity of liver enzymes3, deviations from the norm in indicators of the functional state of the liver2, liver damage, mainly hepatocellular3.

Dermatological reactions: uncommon - skin rash1, itching1; unknown frequency (post-marketing experience with use) - maculopapular, erythematous or exfoliative rash2, urticaria2, pruritus2, angioedema2, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)2, drug hypersensitivity syndrome, drug rash with eosinophilia and systemic manifestations (DRESS syndrome)2, eczema2, lichen planus2.

Allergic reactions: unknown frequency (post-marketing experience) - anaphylactoid reactions2, serum sickness2, cross-hypersensitivity reactions with other thienopyridines (such as ticlopidine, prasugrel)2, anaphylactic shock3, increased symptoms of food allergy3.

Mental disorders: unknown frequency (post-marketing experience) - confusion2, hallucinations2.

From the cardiovascular system: unknown frequency (post-marketing experience) - vasculitis2, decreased blood pressure2.

From the respiratory system: unknown frequency (post-marketing experience of use) - bronchospasm2, interstitial pneumonitis2, eosinophilic pneumonia2, non-cardiogenic pulmonary edema with constant use of the drug associated with a hypersensitivity reaction3.

From the musculoskeletal system: unknown frequency (post-marketing experience) - arthralgia2, arthritis2, myalgia2.

From the urinary system: unknown frequency (post-marketing experience of use) - glomerulopathy, including glomerulonephritis2, acute renal dysfunction (especially in patients with pre-existing renal failure, decompensated chronic heart failure, nephritic syndrome or in patients simultaneously taking diuretics)3.

General disorders: unknown frequency (post-marketing experience) - fever2.

Laboratory and instrumental data: unknown frequency (post-marketing experience of use) - deviation from the norm in indicators of the functional state of the liver2, increased concentration of creatinine in the blood2.

From the metabolic side: unknown frequency (post-marketing experience of use) - hypoglycemia3, gout3.

On the part of the hearing organ: unknown frequency (post-marketing experience of use) - hearing loss3, tinnitus3.

There are no data regarding overdose.

An overdose of clopidogrel can lead to an increase in bleeding time with subsequent complications in the form of bleeding. If bleeding occurs, appropriate treatment is required. No antidote for clopidogrel has been established. If rapid correction of prolonged bleeding time is necessary, platelet transfusion is recommended.

Symptoms of a moderate overdose of ASA: dizziness, ringing in the ears, headache, confusion and gastrointestinal symptoms (nausea, vomiting and stomach pain).

Severe overdose of ASA: severe disturbances in acid-base balance occur. Initially, the resulting hyperventilation leads to the development of respiratory alkalosis, then respiratory acidosis develops as a consequence of the inhibitory effect of respiratory alkalosis on the respiratory center. Also, due to the presence of salicylates in the blood, metabolic acidosis develops. In addition, the following symptoms appear: hyperthermia and profuse sweating, leading to dehydration, restlessness, convulsions, hallucinations and the development of hypoglycemia. Suppression of the nervous system can lead to the development of coma, collapse and respiratory arrest. The lethal dose of ASA is 25-30 g. A plasma concentration of salicylate over 300 mg/l (1.67 mmol/l) confirms the presence of intoxication. In acute and chronic overdose of ASA, non-cardiogenic pulmonary edema may develop.

If symptoms of a severe overdose of acetylsalicylic acid are detected, hospitalization is required. In case of moderate intoxication, you can try to artificially induce vomiting; if unsuccessful, gastric lavage is indicated. After this, activated charcoal and a saline laxative should be taken orally (if the patient can swallow) or administered into the stomach through a tube. In order to force the alkalinization of urine to accelerate the excretion of salicylates, intravenous drip administration of 250 mmol of sodium bicarbonate is indicated for 3 hours under the control of urine pH and acid-base balance. The preferred treatment for severe overdose is hemodialysis or peritoneal dialysis. If necessary, symptomatic treatment of other manifestations of intoxication is used.

Coplavix®

Medicines whose use is associated with a risk of bleeding

There is an increased risk of bleeding due to their potential additive effects with clopidogrel. Treatment should be carried out with caution.

Nikorandil

Patients concomitantly taking nicorandil and NSAIDs, including ASA and lysine acetylsalicylate, have an increased risk of developing severe complications, such as the formation of ulcers and perforations in the gastrointestinal tract and gastrointestinal bleeding (see section "Special Instructions").

Thrombolytics

The safety of concomitant use of clopidogrel, fibrin-specific or non-fibrin-specific thrombolytic agents and heparin was analyzed in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that observed with the simultaneous use of thrombolytic agents and heparin with ASA. Due to the lack of clinical data on the simultaneous use of clopidogrel and thrombolytic agents, caution should be exercised when using them simultaneously (see section "Special Instructions").

Glycoprotein IIb/IIIa inhibitors

Between glycoprotein IIb/IIIa inhibitors, which requires caution when using them simultaneously.

Heparin

According to a clinical study conducted with healthy volunteers, when taking clopidogrel, no change in the dose of heparin was required, and its anticoagulant effect did not change. Concomitant use of heparin did not change the inhibitory effect of clopidogrel on platelet aggregation. There may be a pharmacodynamic interaction between clopidogrel and heparin, which may increase the risk of bleeding, and therefore their simultaneous use requires caution (see section "Special Instructions").

Indirect anticoagulants

The simultaneous use of clopidogrel and oral anticoagulants (warfarin) may increase the intensity of bleeding, and therefore the use of this combination is not recommended.

Clopidogrel at a dose of 75 mg does not affect the pharmacokinetics of warfarin and does not change the International Normalized Ratio (INR) value in patients taking warfarin for a long time. However, concomitant use of warfarin with clopidogrel may increase the risk of bleeding due to the independent effects of these drugs on hemostasis.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

In a clinical study conducted in healthy volunteers, concomitant use of clopidogrel and naproxen increased occult gastrointestinal blood loss. Therefore, the use of NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors, in combination with clopidogrel is not recommended (see section "Special Instructions").

Experimental evidence suggests that ibuprofen (given as a single 400 mg dose between 8 hours before and 30 minutes after immediate administration of 81 mg immediate-release ASA) may inhibit the effect of low-dose ASA on platelet aggregation. However, if ibuprofen is not taken regularly, no clinically significant effects on the antiplatelet effect of ASA are expected.

Selective serotonin reuptake inhibitors (SSRIs)

Since SSRIs impair platelet activation and increase the risk of bleeding, concomitant use of SSRIs with clopidogrel should be done with caution.

Other combination therapy with clopidogrel

Potent and moderate inhibitors of the CYP2C19 isoenzyme

Since clopidogrel is metabolized to its active metabolite in part by the CYP2C19 isoenzyme, it is expected that the use of drugs that inhibit the activity of this isoenzyme may lead to a decrease in the concentration of the active metabolite of clopidogrel. The clinical significance of this interaction is unknown. As a precaution, concomitant use of clopidogrel and strong or moderate inhibitors of the CYP2C9 isoenzyme should be avoided.

Potent and moderate inhibitors of the CYP2C9 isoenzyme are omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, chloramphenicol.

Concomitant use with clopidogrel of proton pump inhibitors that are strong or moderate inhibitors of the CYP2C19 isoenzyme (for example, omeprazole, esomeprazole) is not recommended. If the patient still needs to use a proton pump inhibitor while taking clopidogrel, then a proton pump inhibitor with a minor effect on the activity of the CYP2C19 isoenzyme, such as pantoprazole or lansoprazole, should be used.

Medicines that are substrates of the CYP2C8 isoenzyme

Clopidogrel increased the systemic exposure of repaglinide in healthy volunteers. In vitro studies

showed that the increase in systemic exposure of repaglinin is a consequence of inhibition of the CYP2C8 isoenzyme by the glucuronide metabolite of clopidogrel. Caution should be exercised during the simultaneous use of clopidogrel and drugs that are predominantly eliminated from the body by metabolism via the CYP2C8 isoenzyme (for example, repaglinide, paclitaxel).

A number of clinical studies have been conducted with clopidogrel and other concomitantly administered drugs to examine possible pharmacodynamic and pharmacokinetic interactions, which have shown that:

- when clopidogrel was used simultaneously with atenolol, nifedipine, or with both of these drugs taken simultaneously, no clinically significant pharmacodynamic interaction was observed;

- simultaneous use of phenobarbital, cimetidine and estrogens did not have a significant effect on the pharmacodynamics of clopidogrel;

— the pharmacokinetic parameters of digoxin and theophylline did not change when they were used simultaneously with clopidogrel;

- antacid drugs did not reduce the absorption of clopidogrel;

- Phenytoin and tolbutamide can be safely used concomitantly with clopidogrel (CAPRIE study), although data obtained from studies with human liver microsomes indicate that the carboxyl metabolite of clopidogrel may inhibit the activity of the CYP2C9 isoenzyme, which may lead to increased plasma concentrations of some drugs, for example, phenytoin, tolbutamide and some NSAIDs, which are metabolized by the CYP2C9 isoenzyme.

Other combination therapy with ASA

ASA has been reported to interact with the following drugs:

— uricosurics (medicines that promote the removal of uric acid) (benzbromarone, probenecid, sulfinpyrazone)

: Caution is required, since ASA can suppress their uricosuric effect due to competition with uric acid at the excretion level;

— methotrexate

: Methotrexate taken in doses greater than 20 mg/week should be used with caution when combined with clopidogrel (due to the presence of ASA in Coplavix®), since ASA may reduce the renal clearance of methotrexate, which in turn may increase its myelotoxic effect (see section “With caution”);

— metamizole

: Metamizole, when used simultaneously with ASA, may reduce the effect of ASA on platelet aggregation. Therefore, this combination should be used with caution in patients taking low-dose ASA for cardioprotection;

— acetazolamide

: Caution is recommended when using salicylates and acetazolamide simultaneously due to an increased risk of developing metabolic acidosis;

— chickenpox vaccine:

It is recommended that patients not take salicylates for 6 months after chickenpox vaccination, as cases of Reye's syndrome after taking salicylates have been observed during chickenpox infection (see section "Special Instructions").

— levothyroxine sodium

: Salicylates, especially at doses greater than 2.0 g/day, may inhibit the binding of thyroid hormones to carrier proteins and therefore lead to an initial transient increase in concentrations of free thyroid hormones followed by a decrease in their concentrations. Thyroid hormone concentrations should be monitored (see section "Special Instructions").

— valproic acid:

simultaneous use of valproic acid and salicylates can lead to a decrease in the binding of valproic acid to blood proteins and inhibition of the metabolism of valproic acid, leading to an increase in the total serum concentration of valproic acid and the serum concentration of its free fraction.

— tenofovir

: Concomitant use of tenofovir disoproxil fumarate and NSAIDs may increase the risk of developing renal failure.

— Angiotensin-converting enzyme (ACE) inhibitors, anticonvulsants (phenytoin and valproic acid), beta-blockers, diuretics and oral hypoglycemic agents:

possible interactions of these drugs with ASA, used in high (anti-inflammatory) doses;

— ethanol

: when used simultaneously with ASA, the risk of bleeding increases with chronic consumption of large quantities of alcohol (ethanol). In addition, ethanol may increase the risk of gastrointestinal damage when using ASA. Therefore, patients taking ASA should drink alcohol (ethanol) with caution (see section "Special Instructions").

Other interactions with clopidogrel and ASA

- Diuretics, beta-blockers, ACE inhibitors, slow calcium channel blockers, lipid-lowering drugs, coronary vasodilators, hypoglycemic drugs (including insulin), antiepileptic drugs, GPIIb/IIIa glycoprotein receptor blockers and hormone replacement therapy

In clinical studies of the use of clopidogrel in combination with ASA at maintenance doses ≤ 325 mg, conducted in more than 30,000 patients, no clinically significant adverse interactions with these drugs were identified.

— Opioid agonists

As with other oral P2Y12 inhibitors, concomitant use of opioid agonists may decrease the absorption of clopidogrel, possibly due to delayed gastric emptying. The clinical significance of this interaction is unknown. A parenteral antiplatelet agent should be considered in patients with acute coronary syndrome requiring concomitant use of morphine or other opiate agonists.

Coplavix, 100 pcs., 100 mg+75 mg, film-coated tablets

The safety of clopidogrel in clinical studies has been studied in more than 44,000 patients, incl. in more than 12,000 patients taking it for a year or more, and in 30,000 patients taking both clopidogrel and ASA; in the CURE

The safety of clopidogrel in combination with ASA was assessed in more than 6,200 patients who took them for 1 year or more.

The following are clinically significant adverse events (AEs) observed in five large clinical trials: CAPRIE, CURE, CLARITY, COMMIT

and
ACTIVE A
and with post-marketing use of the combination of clopidogrel + ASA, clopidogrel in monotherapy and ASA in monotherapy.

The incidence of side effects was determined according to the WHO classification: very common >10%; often >1 and <10%; uncommon >0.1 and <1%; rarely >0.01 and <0.1%; very rare <0.01%; frequency unknown - it is not possible to determine the frequency of NE from the available data.

Conventions.

1NE that were observed when using a combination of clopidogrel and ASA. 2 AEs that were observed with the use of clopidogrel. 3NEs that were observed with the use of ASA.

Hemorrhagic adverse events (purpura/bruising; nosebleeds; hematuria; hemorrhages in the skin, bone and muscle tissue; hematomas; hemorrhages in the joint cavity (hemarthrosis), conjunctiva, internal media and retina; bleeding from the respiratory tract, hemoptysis; bleeding from a surgical wound; intracranial hemorrhages (hemorrhagic strokes); bleeding from the gastrointestinal tract, retroperitoneal hemorrhages, etc.)

Bleeding and hemorrhage were the most commonly observed adverse events in clinical studies and post-marketing use of the drug, mainly occurring during the 1st month of treatment: common - major bleeding1 (life-threatening bleeding requiring transfusion of 4 or more units of blood; other major bleeding requiring transfusion of 2–3 units of blood; non-life-threatening major bleeding (in the
COMMIT

ACTIVE-A
study, the incidence of minor bleeding was “very often")1, bleeding at the site of vascular puncture1,2; bruises2; hematomas2. The frequency of major bleeding when using the combination of clopidogrel + ASA depended on the dose of ASA (<100 mg - 2.6%; 100-200 mg - 3.5%, >200 mg - 4.9%), as well as their frequency when using ASA alone (<100 mg - 2%, 100-200 mg - 2.3%, >200 mg - 4%). In patients who stopped treatment more than 5 days before coronary artery bypass surgery, there was no increase in the incidence of major bleeding within 7 days after this intervention (4.4% when taking clopidogrel + ASA versus 5.3% when taking ASA alone).
In patients who remained on antiplatelet therapy during the last five days before coronary artery bypass surgery, the incidence of these bleedings after surgery was 9.6% (clopidogrel + ASA) and 6.3% (ASA alone); uncommon - fatal bleeding1; life-threatening bleeding (bleeding with a decrease in blood hemoglobin of more than 5 g/dl (according to the CLARITY clinical trial, the incidence was “common”)1; bleeding requiring surgical intervention1; intracranial hemorrhage (hemorrhagic stroke) (according to the clinical trial CLARITY,
the incidence of their development was “common”)1; bleeding requiring the administration of inotropic drugs)1; severe bleeding (purpura and nosebleeds were the most common; hematuria and intraocular hemorrhages, mainly conjunctival, were less common2); rarely - intraocular hemorrhages with significant visual impairment1, retroperitoneal hemorrhages1; frequency unknown (post-marketing experience) - serious cases of bleeding2, mainly hemorrhages in skin tissue2, bone, muscle and joint cavity (hemarthrosis)2, in eye tissue (conjunctival, in the internal media and retina of the eye)2, bleeding from the respiratory tract2 , hemoptysis2, nosebleeds2, hematuria2, bleeding from the surgical wound2; intracranial hemorrhage3, including fatal cases3, especially in elderly patients; other cases of fatal bleeding (in particular bleeding from the gastrointestinal tract and retroperitoneal hemorrhage)2.

From the blood and lymphatic system:

uncommon - decreased platelet count in peripheral blood1, severe thrombocytopenia with platelet count in peripheral blood <80·109/l, but >30·109/l1; leukopenia1; decrease in the number of neutrophils in peripheral blood1, eosinophilia1, prolongation of bleeding time1; rarely - neutropenia1, including severe neutropenia (<0.451·109/l)1. Although the risk of myelotoxicity with clopidogrel is low, the possibility should be considered when a patient taking clopidogrel develops fever and other infectious manifestations; very rarely - aplastic anemia1, severe thrombocytopenia with a platelet count in peripheral blood <30·109/l1; frequency unknown (post-marketing experience) - thrombocytopenia3, hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency3, agranulocytosis2,3; aplastic anemia2,3/pancytopenia2,3, bicytopenia3, disorders of bone marrow hematopoiesis3, neutropenia3, leukopenia3, granulocytopenia3, anemia1, acquired hemophilia A2, thrombotic thrombocytopenic purpura (TTP)2.

From the central and peripheral nervous system:

uncommon - headache1, dizziness1 and paresthesia1; rarely - vertigo1; frequency unknown (post-marketing experience of use) - changes in taste sensations2.

From the digestive system:

often - gastrointestinal bleeding1, dyspepsia1, abdominal pain1, diarrhea1; uncommon - nausea1, gastritis1, flatulence1, constipation1, vomiting1, gastric ulcer1 and duodenal ulcer1; frequency unknown (post-marketing experience) - colitis2,3 (including ulcerative or lymphocytic colitis)2, pancreatitis2, stomatitis2, esophagitis3, ulceration/perforation of the esophagus3, erosive gastritis3, erosive duodenitis3, ulcer or ulcerative perforation of the stomach and/or duodenum3, symptoms of damage upper gastrointestinal tract, such as gastralgia3 (see "Special Instructions"), ulcers of the small intestine (jejunum and ileum)3 and large intestine (colon and rectum)3, intestinal perforation3 (these reactions may or may not be accompanied by bleeding and may occur when using any dose of ASA, as well as in patients with or without warning symptoms and a history of serious gastrointestinal complications); acute pancreatitis, which is a manifestation of a hypersensitivity reaction to acetylsalicylic acid3.

From the liver and biliary tract:

frequency unknown (post-marketing experience of use) - hepatitis (non-infectious nature)2, acute liver failure2, increased activity of liver enzymes3, liver damage, mainly hepatocellular3, chronic hepatitis3.

For the skin and subcutaneous tissues:

uncommon - skin rash1, itching1; frequency unknown (post-marketing experience) - macular-papular, erythematous or exfoliative skin rash2, urticaria2, itching2, angioedema2, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)2, acute generalized exanthematous pustulosis, drug hypersensitivity syndrome , drug rash with eosinophilia and systemic manifestations (DRESS syndrome)2, eczema2 lichen planus2, fixed skin rash (single or multiple skin changes, usually in the form of erythematous plaques of a round or oval shape, appearing in the same place with the next dose of the drug )3.

From the immune system:

frequency unknown (post-marketing experience): anaphylactoid reactions2, serum sickness2, hypersensitivity cross-reactions with other thienopyridines (such as ticlopidine, prasugrel)2 (see “Special Instructions”), anaphylactic shock3, increased symptoms of food allergy3.

Mental disorders:

frequency unknown (post-marketing experience) - confusion2, hallucinations2.

From the side of blood vessels:

frequency unknown (post-marketing experience of use) - vasculitis2,3, including Henoch-Schönlein purpura3, decreased blood pressure2.

From the heart:

frequency unknown (post-marketing experience) - Kounis syndrome (allergic coronary syndrome), caused by a hypersensitivity reaction to ASA3.

From the respiratory system, chest and mediastinal organs:

frequency unknown (post-marketing experience) - bronchospasm2, interstitial pneumonitis2, eosinophilic pneumonia2, non-cardiogenic pulmonary edema with chronic use of the drug associated with a hypersensitivity reaction3.

From the musculoskeletal and connective tissue side:

frequency unknown (post-marketing experience) - arthralgia2, arthritis2, myalgia2.

From the kidneys and urinary tract:

frequency unknown (post-marketing experience) - glomerulopathy, including glomerulonephritis2, acute renal failure (especially in patients with pre-existing renal failure, decompensated CHF, nephritic syndrome or in patients simultaneously taking diuretics)3, renal failure3.

Common disorders:

frequency unknown (post-marketing experience) - fever2.

From the genital organs and breast:

frequency unknown (post-marketing experience) - gynecomastia2.

Laboratory and instrumental data:

frequency unknown (post-marketing experience of use) - deviation from the norm in biochemical indicators of the functional state of the liver2, increase in the concentration of creatinine in the blood2.

Metabolism and nutrition:

frequency unknown (post-marketing experience) - hypoglycemia3, gout3.

Hearing and labyrinth disorders:

frequency unknown (post-marketing experience) - hearing loss3, tinnitus3.

General disorders and disorders at the injection site:

edema, which has been reported when taking ASA in high (anti-inflammatory) doses.