Cardiomagnyl forte film-coated tablets 150 mg bottle No. 100

Instructions Cardiomagnyl forte film-coated tablets 150 mg bottle No. 100

Composition

active ingredient: acetylsalicylic acid;

1 tablet contains 150 mg of acetylsalicylic acid;

excipients: corn starch, magnesium hydroxide, microcrystalline cellulose, magnesium stearate, potato starch, hypromellose, propylene glycol, talc.

Dosage form

Film-coated tablets.

Main physicochemical properties: film-coated tablets, white, oval in shape with a score on one side.

Pharmacotherapeutic group

Antithrombotic agents. Platelet aggregation inhibitors, excluding heparin. ATX code B01A C06.

Pharmacological properties

Pharmacodynamics

Acetylsalicylic acid is an analgesic, anti-inflammatory, antipyretic, and antiplatelet agent. Antiplatelet properties increase bleeding time.

The main pharmacological effect is the inhibition of prostaglandin and thromboxane formation. The analgesic effect is an additional effect caused by inhibition of the cyclooxygenase enzyme. The anti-inflammatory effect is associated with reduced blood flow caused by inhibition of PGE2 synthesis.

Acetylsalicylic acid irreversibly inhibits the synthesis of prostaglandins G/H, its effect on platelets lasts longer than acetylsalicylic acid is in the body. The effect of acetylsalicylic acid on the biosynthesis of thromboxane in platelets and on bleeding time continues for a long time after discontinuation of treatment. The effect ceases only after the appearance of new platelets in the blood plasma.

Salicylic acid (the active metabolite of acetylsalicylic acid) has an anti-inflammatory effect and also affects respiratory processes, acid-base balance and gastric mucosa. Salicylates stimulate respiration, mainly by exerting a direct effect on the bone marrow. Salicylates exert an indirect effect on the gastric mucosa by inhibiting its vasodilator and cytoprotective prostaglandins and increase the risk of ulcers.

Pharmacokinetics

Absorption. After oral administration, acetylsalicylic acid is rapidly absorbed from the gastrointestinal tract. After oral administration, the absorption of the unionized form of acetylsalicylic acid occurs in the stomach and intestines. The rate of absorption is reduced by food intake and in patients with migraine attacks, and increased in patients with achlorhydria or in patients taking polysorbates or antacids. The maximum concentration in the blood serum is reached after 1–2 hours.

Distribution. The binding of acetylsalicylic acid to plasma proteins is 80–90%. The volume of distribution in adults is 170 ml/kg body weight. With increasing plasma concentration, saturation of the active sites of proteins occurs, which leads to an increase in the volume of distribution. Salicylates are extensively bound to plasma proteins and are rapidly distributed throughout the body. Salicylates penetrate into breast milk and can penetrate the placental barrier.

Metabolism: Acetylsalicylic acid is hydrolyzed to the active metabolite, salicylic acid, in the stomach wall. After absorption, acetylsalicylic acid is rapidly converted to salicylic acid, but within the first 20 minutes after oral administration it is dominant in the blood plasma.

Excretion. Salicylic acid is metabolized mainly in the liver. Thus, the equilibrium concentration of salicylic acid in the blood plasma increases disproportionately to the dose taken orally. In the case of taking 325 mg of acetylsalicylic acid, excretion occurs with the participation of first-order reaction kinetics. The half-life is 2–3 hours. With a high dose of acetylsalicylic acid, the half-life increases to 15–30 hours. Salicylic acid is also excreted unchanged in the urine.

The amount of salicylic acid excreted depends on the dose and urine pH. Approximately 30% of the dose of salicylic acid is excreted in the urine if the urine reaction is alkaline, only 2% if it is acidic. Renal excretion occurs through the processes of glomerular filtration, active renal tubular secretion, and passive tubular reabsorption.

Indication

Acute and chronic ischemic heart disease.

Contraindication

The drug Cardiomagnyl Forte is contraindicated in the following conditions/diseases:

Known or suspected hypersensitivity to acetylsalicylic acid, other salicylates, non-steroidal anti-inflammatory drugs (NSAIDs) or to any component of the drug. Bleeding tendency (vitamin K deficiency, thrombocytopenia, hemophilia). Acute peptic ulcers. Severe renal failure (glomerular filtration rate < 0.2 ml/s (10 ml/min)). Severe hepatic failure. Severe heart failure. Third trimester of pregnancy (see section "Use during pregnancy and lactation").

Interaction with other medicinal products and other types of interactions

Methotrexate. The use of acetylsalicylic acid and methotrexate in doses of 15 mg/week or more increases the hematological toxicity of methotrexate (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).

ACE inhibitors. Angiotensin-converting enzyme inhibitors in combination with high doses of acetylsalicylic acid cause a decrease in glomerular filtration due to inhibition of the vasodilator effect of prostaglandins and a decrease in the antihypertensive effect.

Acetazolamide: Possible increase in acetazolamide concentrations may result in the penetration of salicylates from plasma into tissue and cause acetazolamide toxicity (fatigue, lethargy, drowsiness, confusion, hyperchloremic metabolic acidosis) and salicylate toxicity (vomiting, tachycardia, hyperpnea, confusion).

Probenecid, sulfinpyrazone. When probenecid is used with high doses of salicylates (> 500 mg), the metabolism of both drugs is inhibited and uric acid excretion may be reduced.

Combinations that should be used with caution.

Clopidogrel, ticlopidine. The combined use of clopidogrel and acetylsalicylic acid has a synergistic effect. Such combined use should be carried out with caution, as it increases the risk of bleeding.

Anticoagulants (warfarin, phenprocoumon). Thrombin production may be reduced, resulting in an indirect effect on platelet activity (vitamin K antagonist) and an increased risk of bleeding.

Abciximab, tirofiban, eptifibatide. Possible inhibition of glycoprotein IIb/IIIa receptors on platelets, leading to an increased risk of bleeding.

Heparin: May reduce thrombin production, resulting in an indirect effect on platelet activity, leading to an increased risk of bleeding.

If two or more of the above substances are used together with acetylsalicylic acid, this may lead to a synergistic effect of increased inhibition of platelet activity and, as a result, increased hemorrhagic diathesis.

NSAIDs and COX-2 inhibitors (celecoxib). Concomitant use increases the risk of gastrointestinal disorders, which may lead to gastrointestinal bleeding.

Ibuprofen: Concomitant use of ibuprofen inhibits irreversible platelet aggregation induced by acetylsalicylic acid. Treatment with ibuprofen in patients at increased risk of cardiovascular events may limit the cardioprotective effect of acetylsalicylic acid.

Patients who take acetylsalicylic acid once a day for the prevention of cardiovascular disease and occasionally take ibuprofen should take acetylsalicylic acid at least 2 hours before taking ibuprofen.

Furosemide: Inhibition of proximal tubular elimination of furosemide is possible, leading to a decrease in the diuretic effect of furosemide.

Quinidine: May have an additive effect on platelets, leading to prolonged bleeding time.

Spironolactone: Possible modified renin effect, leading to reduced efficacy of spironolactone.

Selective serotonin reuptake inhibitors: Concomitant use increases the risk of gastrointestinal disorders, which may lead to gastrointestinal bleeding.

Valproate. When used simultaneously with valproate, acetylsalicylic acid displaces it from its association with blood plasma proteins, increasing the toxicity of the latter (central nervous system depression, gastrointestinal disorders).

Systemic glucocorticosteroids (with the exception of hydrocortisone, which is used for replacement therapy in Addison's disease) reduce the level of salicylates in the blood and increase the risk of salicylate overdose after discontinuation of glucocorticosteroid therapy.

Antidiabetic drugs. Concomitant use of acetylsalicylic acid and antidiabetic drugs increases the risk of hypoglycemia.

Antacids. Possible increase in renal clearance and decrease in renal absorption (due to increased urine pH), which leads to a decrease in the effect of acetylsalicylic acid.

Varicella vaccine. Concomitant use increases the risk of Reye's syndrome.

Ginkgo biloba. Concomitant use with ginkgo biloba inhibits platelet aggregation, which leads to an increased risk of bleeding.

Digoxin. When used simultaneously with digoxin, the concentration of the latter in the blood plasma increases due to a decrease in renal excretion.

Alcohol contributes to damage to the gastrointestinal mucosa and prolongs bleeding time due to the synergism of acetylsalicylic acid and alcohol.

Metamizole.

The simultaneous use of acetylsalicylic acid and metamizole may reduce the clinically significant level of platelet aggregation. Therefore, the combination of drugs containing acetylsalicylic acid and metamizole should be used with caution in patients taking low-dose aspirin for cardioprotection.

Application features

Long-term use of the drug in elderly patients for the treatment of pain, inflammation, fever or rheumatic diseases is not recommended due to the risk of gastrointestinal bleeding. Given the risk of gastrointestinal bleeding in elderly patients, caution should be exercised when using low doses of acetylsalicylic acid for the treatment of acute or chronic ischemic heart disease, stroke, or prevention of stroke or ischemic heart disease.

The drug Cardiomagnyl Forte is used with caution in the following situations:

diseases of the gastrointestinal mucosa; tendency to dyspepsia;

concomitant treatment with anticoagulants (vitamin K antagonists and heparin (see section "Interaction with other medicinal products and other types of interactions")).

Hypersensitivity to analgesics, anti-inflammatory, antirheumatic drugs, as well as allergies to other substances; gastrointestinal ulcers, including chronic and recurrent ulcers or a history of gastrointestinal bleeding; concomitant use of anticoagulants; impaired renal function or cardiovascular circulation (e.g. renal vascular disease, congestive heart failure, hypovolemia, extensive surgery, sepsis or severe bleeding), as acetylsalicylic acid may also increase the risk of impaired renal function and acute renal failure; severe glucose-6-phosphate dehydrogenase deficiency, as acetylsalicylic acid may cause hemolysis or hemolytic anemia; especially in the presence of factors that may increase the risk of hemolysis (high doses of the drug, fever or acute infectious process); impaired liver function.

Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. In the case of using the drug Cardiomagnyl Forte, the patient should consult a doctor before starting to take ibuprofen as an analgesic.

Acetylsalicylic acid may cause 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, and a history of allergic reactions (e.g. skin reactions, itching, urticaria) to other substances.

Due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after administration, the use of drugs containing acetylsalicylic acid may increase the likelihood of increased bleeding during surgical operations (including minor surgical interventions, such as tooth extraction).

When using low doses of acetylsalicylic acid, the excretion of uric acid may be reduced. This may lead to an attack of gout in patients prone to it.

Do not use acetylsalicylic acid-containing products in children and adolescents with acute respiratory viral infections (ARI), with or without fever, without consulting a doctor. Some viral diseases, especially influenza A, influenza B and chickenpox, carry a risk of developing Reye's syndrome, which is a very rare but life-threatening illness requiring immediate medical attention. The risk may be increased if acetylsalicylic acid is used as a concomitant medication, but a causal relationship has not been proven in this case. If these conditions are accompanied by persistent vomiting, this may be a manifestation of Reye's syndrome.

If the risk of increased bleeding outweighs the risk of ischemia, consideration should be given to temporarily discontinuing treatment with low doses of Cardiomagnyl Forte a few days before the scheduled surgery.

Fertility: The use of acetylsalicylic acid may impair fertility and is therefore not recommended in women attempting to conceive. Discontinuation of acetylsalicylic acid should be considered in women who are unable to conceive or are undergoing investigation of infertility (see section "Use during pregnancy and lactation").

Ability to influence reaction speed when driving vehicles or other mechanisms

Cardiomagnyl Forte has no or negligible effect on the reaction rate when driving vehicles and other mechanisms.

Use during pregnancy or breastfeeding

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Available epidemiological data indicate a risk of miscarriage and foetal malformations after the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with increasing dose and duration of therapy. According to the available data, the association between the use of acetylsalicylic acid and an increased risk of miscarriage has not been confirmed.

The available epidemiological data on the occurrence of malformations 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) involving approximately 14,800 mother-child pairs 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 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.

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); renal dysfunction with possible further development of renal failure with oligohydramnios.

Prostaglandin synthesis inhibitors can affect a woman and her baby at the end of pregnancy in the following ways:

Possible prolongation of bleeding time, antiplatelet effect, which may occur even after very low doses; inhibition of uterine contractions, which may lead to delayed or prolonged labor.

Given this, acetylsalicylic acid is contraindicated during the third trimester of pregnancy.

Salicylates and their metabolites pass into breast milk in small quantities.

Since no harmful effects on the child have been identified after administration of the drug by a woman during lactation, interruption of breastfeeding is usually not necessary. However, in the case of regular use or when using high doses, breastfeeding should be discontinued early.

Fertility.

Acetylsalicylic acid should not be used in women attempting to conceive, as prostaglandin synthesis inhibitors reduce fertility.

If acetylsalicylic acid is necessary, the duration of treatment should be as short as possible and the dose should be as low as possible. The effect on fertility is reversible.

Method of administration and doses

The drug is intended for oral use.

The recommended dose for adults is 150 mg (1 tablet) per day.

The tablets are swallowed whole, with water if necessary. To ensure rapid absorption, the tablet can be chewed or dissolved in water.

Hepatic impairment. The drug should not be used in patients with severe hepatic impairment. Dosage adjustment may be necessary in patients with hepatic impairment.

Renal impairment: Do not use in patients with severe renal impairment (glomerular filtration rate < 0.2 mL/s (10 mL/min)). Dosage adjustment may be necessary in patients with renal impairment.

Children

According to the indicated indications (see the section "Method of administration and dosage"), the drug Cardiomagnyl Forte is not used in children.

The use of acetylsalicylic acid in children under 15 years of age can cause severe side effects (including Reye's syndrome, one of the signs of which is persistent vomiting).

For detailed information, see the "Application Features" section.

Overdose

Toxicity.

Unsafe dose. Adults: 300 mg/kg body weight. Children: single dose of 150 mg/kg or more than 100 mg/kg per day for more than 2 days.

Chronic salicylate poisoning can be insidious because its signs and symptoms are nonspecific. Moderate chronic salicylate intoxication, or salicylism, usually occurs only after repeated ingestion of large doses.

Symptoms of chronic moderate poisoning (resulting from prolonged use of high doses of the drug): dizziness, vertigo, deafness, increased sweating, fever, rapid breathing, tinnitus, respiratory alkalosis, metabolic acidosis, lethargy, moderate dehydration, headache, confusion, nausea and vomiting.

Acute intoxication is evidenced by a pronounced change in acid-base balance, which may vary depending on age and 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, due to the formation of concrements in the stomach or when the drug is taken in the form of enteric-coated tablets.

Symptoms of severe and acute poisoning (due to overdose): hypoglycemia (mainly in children), encephalopathy, coma, hypotension, pulmonary edema, convulsions, coagulopathy, cerebral edema, cardiac arrhythmias.

Acute salicylate poisoning (> 300 mg/kg) often causes acute renal failure, and a dose of 500 mg/kg can be fatal.

A more pronounced toxic effect is observed in patients with chronic overdose or abuse of the drug, as well as in elderly patients or children.

Treatment. In case of acute overdose, gastric lavage and administration of activated charcoal are necessary. If a dose greater than 120 mg/kg body weight is suspected, activated charcoal should be administered again.

Serum salicylate levels should be measured at least every 2 hours after dosing until salicylate levels are consistently reduced and acid-base balance is restored.

It is necessary to restore the balance of fluids and electrolytes. Effective methods of removing salicylate from the blood plasma are alkaline diuresis and hemodialysis. Hemodialysis should be used in case of severe intoxication, since this method significantly accelerates the elimination of salicylate and restores the acid-base and water-salt balances.

Due to the complex pathophysiological effects of salicylate poisoning, signs and symptoms/test results may include:

Adverse reactions

The most common adverse events are gastrointestinal disorders.

Adverse events are usually dose- and duration-dependent.

The information on adverse reactions provided is based on spontaneous post-marketing reports of adverse reactions with all pharmaceutical forms and dosages of acetylsalicylic acid (including oral administration during short and long-term treatment).

Adverse events are classified by frequency of occurrence into the following categories: very common (> 1/10), common (> 1/100 and < 1/10), uncommon (> 1/1000 and < 1/100), rare (> 1/10000 and < 1/1000), very rare (< 1/10000).

Research.

Very common: increased bleeding time.

Rare: increased transaminase and alkaline phosphatase levels.

From the blood and lymphatic system.

Very common: inhibition of platelet aggregation.

Common: prolonged bleeding time.

Uncommon: occult bleeding.

Rare: anemia with long-term treatment, hemolysis in congenital glucose-6-phosphate dehydrogenase deficiency.

Very rare: hypoprothrombinemia (high doses), thrombocytopenia, neutropenia, eosinophilia, agranulocytosis, aplastic anemia.

From the nervous system.

Common: headache.

Uncommon: dizziness, drowsiness.

Rare: intracerebral hemorrhage.

From the ear and labyrinth.

Uncommon: tinnitus.

Rare: dose-related reversible hearing loss and deafness (with lower plasma concentrations of salicylates).

On the part of the respiratory system.

Common: bronchospasm in patients with asthma (see section "Special warnings and precautions for use").

Uncommon: shortness of breath, allergic reactions (rhinitis, nasal congestion).

From the gastrointestinal tract.

Very common: heartburn, acid reflux, epigastric pain and abdominal pain.

Common: erosive-inflammatory lesions of the upper gastrointestinal tract, nausea, dyspepsia, vomiting and diarrhea.

Uncommon: upper gastrointestinal ulcer and bleeding, haematemesis and melena.

Due to its antiplatelet effect on platelets, acetylsalicylic acid may be associated with a risk of bleeding and prolongation of bleeding time. Bleeding events such as perioperative hemorrhages, hematomas, genitourinary bleeding, epistaxis, and gingival bleeding have been observed.

Rare: serious upper gastrointestinal bleeding, such as gastrointestinal haemorrhages1, cerebral haemorrhages (especially in patients with uncontrolled hypertension and/or concomitant use of antihaemostatic agents), which in isolated cases could be potentially life-threatening, perforation.

Very rare: stomatitis, esophagitis, toxic lesions of the lower gastrointestinal tract with ulcers, strictures, colitis or exacerbation of inflammatory bowel disease.

Rare: renal dysfunction, development of acute renal failure.

On the skin and subcutaneous tissue.

Uncommon: allergic reactions (urticaria, oedema, pruritus, angioedema2).

Very rare: hemorrhagic rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the endocrine system.

Rare: hypoglycemia.

From the vascular system.

Rare: hemorrhagic vasculitis.

From the immune system.

Uncommon: anaphylactic reactions.

On the part of the hepatobiliary system.

Very rare: dose-related mild reversible toxic hepatitis in some viral diseases (influenza A, B and varicella). Salicylates may be factors in the development of Reye's syndrome in children (see section "Special instructions"). Transient hepatic failure with increased serum transaminases and alkaline phosphatase has been reported.

Mental disorders.

Common: insomnia.

1 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.

2 Angioedema develops more often in patients prone to allergies.

Expiration date

3 years.

Storage conditions

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

Packaging

30 or 100 tablets in a bottle; 1 bottle in a cardboard box.

Vacation category

According to the recipe.

Producer

Takeda GmbH, production site Oranienburg, Germany/Takeda GmbH Betriebsstätte Oranienburg, Germany.

Location of the manufacturer and its business address

Lehnitzstrasse 70-98, 16515 Oranienburg, Germany.