Instructions for use Magnicor forte film-coated tablets, blister pack No. 100
Composition
active ingredient: 1 tablet contains acetylsalicylic acid 150 mg;
excipients: magnesium hydroxide; corn starch; microcrystalline cellulose; potato starch; magnesium stearate;
shell: film-coating mixture Oradry II White ((hypromellose (hydroxypropylmethylcellulose); lactose, monohydrate; polyethylene glycol (macrogol); titanium dioxide (E 171); triacetin)).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, a score, covered with a white or almost white film coating.
Pharmacotherapeutic group
Antithrombotic agents. Platelet aggregation inhibitors, excluding heparin. ATC 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 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 lasts 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 acting directly on the bone marrow. Salicylates have 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 for 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 administered dose. At a dose of 325 mg of acetylsalicylic acid, elimination occurs with the participation of first-order reaction kinetics. The half-life is 2–3 hours. At high doses of acetylsalicylic acid, the half-life increases to 15–30 hours. Salicylic acid is also excreted unchanged in the urine. The excreted volume of salicylic acid depends on the dose level and urine pH. Approximately 30% of the salicylic acid dose is excreted in the urine if the urine reaction is alkaline, only 2% if it is acidic. Excretion through the kidneys occurs due to the processes of glomerular filtration, active secretion of the renal tubules and passive tubular reabsorption.
Indication
Acute and chronic ischemic heart disease.
Contraindication
Hypersensitivity to acetylsalicylic acid, other salicylates or to any component of the drug.
History of asthma induced by the use of salicylates or substances with a similar effect, especially non-steroidal anti-inflammatory drugs (NSAIDs).
Acute peptic ulcers.
Hemorrhagic diathesis.
Severe renal failure.
Severe liver failure.
Severe heart failure.
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
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).
Combinations for simultaneous use are not recommended.
Uricosurics (probenecid, sulfinpyrazone). The use of probenecid and high doses of salicylates (> 500 mg) inhibits the metabolism of both drugs and may reduce uric acid excretion. Therefore, this combination should be avoided.
Combinations that should be used with caution.
Methotrexate. When using acetylsalicylic acid and methotrexate in doses less than 15 mg/week, the hematological toxicity of methotrexate increases (reduction in renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).
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 use acetylsalicylic acid once a day for the prevention of cardiovascular disease and occasionally use ibuprofen should use acetylsalicylic acid at least 2 hours before using ibuprofen.
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 with cyclosporine or tacrolimus may increase the nephrotoxicity of cyclosporine and tacrolimus. When these drugs are used simultaneously with acetylsalicylic acid, renal function should be monitored.
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.
Antiepileptic drugs (valproate, phenytoin). 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 (excluding hydrocortisone, which is used for replacement therapy in Addison's disease) reduce the level of salicylates in the blood and increase the risk of overdose after the end of treatment.
Antidiabetic drugs: Concomitant use of acetylsalicylic acid and antidiabetic drugs increases the risk of hypoglycemia.
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.
Barbiturates: The concentration of barbiturates in the blood serum may increase when used simultaneously with acetylsalicylic acid.
Penicillin. Prolongation of the plasma half-life of penicillin.
Alcohol contributes to damage to the gastrointestinal mucosa and prolongs bleeding time due to the synergism of acetylsalicylic acid and alcohol.
Application features
The medicine should be used with caution in the following cases:
hypersensitivity to analgesic, anti-inflammatory, antirheumatic drugs, as well as in case of allergies to other substances;
gastrointestinal ulcers, including chronic and recurrent peptic ulcers or a history of gastrointestinal bleeding;
the presence of symptoms of chronic gastric or duodenal dyspepsia or their recurrence;
simultaneous use of anticoagulants;
arterial hypertension;
renal dysfunction or cardiovascular circulatory disorders (for example: renal vascular pathology, congestive heart failure, hypovolemia, extensive surgery, sepsis or severe bleeding) - since acetylsalicylic acid also increases the risk of renal dysfunction and acute renal failure;
liver dysfunction;
Severe glucose-6-phosphate dehydrogenase deficiency – acetylsalicylic acid may cause hemolysis or hemolytic anemia, especially in the presence of risk factors for hemolysis, such as high doses of the drug, fever, or acute infectious process.
Acetylsalicylic acid is not recommended for use in women with menorrhagia (during menstruation) as it may increase menstrual bleeding.
Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. In case of use of the drug, the patient should consult a doctor before starting the use of 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.
There have been rare reports of serious skin reactions, including Stevens-Johnson syndrome, with the use of acetylsalicylic acid (see section 4.8). The drug should be discontinued if any clinical signs of hypersensitivity reactions, including skin and mucous membrane rash, appear.
Due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after use, the use of medicinal products containing acetylsalicylic acid increases the likelihood of bleeding during surgery (including minor surgical interventions, such as tooth extraction).
When using small 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.
Medicines containing acetylsalicylic acid should not be used in children and adolescents with acute respiratory viral infections (ARI), with or without fever, without consulting a doctor. With some viral diseases, especially influenza A, influenza B and chickenpox, there is a risk of developing Reye's syndrome, which is a very rare but life-threatening illness that requires urgent medical intervention. The risk may be increased if acetylsalicylic acid is used as a concomitant medicine, but a causal relationship in this case has not been proven. If these conditions are accompanied by persistent vomiting, this may be a manifestation of Reye's syndrome.
The medicine contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take it.
Use during pregnancy or breastfeeding
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 malformation and gastroschisis) 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, an 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. Available data on its effects in early pregnancy (1-4 months) do not indicate any association with an increased risk of malformations.
Animal studies indicate reproductive toxicity.
During the first and second trimesters of pregnancy, medicines containing acetylsalicylic acid should not be prescribed unless clearly necessary. For women who may be pregnant or during the first and second trimesters of pregnancy, the dose of medicines containing acetylsalicylic acid should be as low as possible and the duration of treatment should be as short as possible.
Animal studies have shown that the use of prostaglandin inhibitors leads to an increase in pre- and post-implantation losses and embryo/fetal death. In addition, an increased incidence of severe malformations, including cardiovascular malformations, has been observed in animals treated with prostaglandin inhibitors during organogenesis.
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 can:
affect the fetus in the following ways:
cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
impaired renal function with possible subsequent development of renal failure with oligohydramnios;
affect the woman and child at the end of pregnancy in the following ways:
prolongation of bleeding time, antiplatelet effect, which may occur even after the use of very low doses;
inhibition of uterine contractions, which can lead to a delay or increase in the duration of labor.
Given this, acetylsalicylic acid is contraindicated in the third trimester of pregnancy.
Breastfeeding. Salicylates and their metabolites pass into breast milk in small amounts. Concentrations in breast milk are equivalent to or even higher than those in maternal plasma.
Since no harmful effects of the drug on the child have been identified after administration to lactating women, interruption of breastfeeding is usually not necessary. However, in cases of regular use or when using high doses (> 300 mg/day), breastfeeding should be discontinued early.
Fertility: There is some evidence that drugs that inhibit prostaglandin synthesis may impair female reproductive function by affecting ovulation. This effect is reversible and disappears after discontinuation of treatment.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effect.
Method of administration and doses
The recommended dose for adults is 1 tablet (150 mg) per day.
Swallow the tablets 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 indications (see the section "Method of administration and dosage"), the drug should not be 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).
Overdose
Toxicity.
Dangerous dose: Adults: 300 mg/kg body weight.
Chronic salicylate poisoning can be insidious because its signs and symptoms are nonspecific. Moderate chronic salicylate intoxication, or salicylism, usually occurs only after repeated administration of large doses.
Acute intoxication is evidenced by a pronounced change in the 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 data on the concentration of salicylates in the blood plasma. The absorption of acetylsalicylic acid may be slowed down due to delayed gastric emptying, the formation of concrements in the stomach or when it is used 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.
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 of more 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.
Prothrombin time and/or INR (international normalized ratio) should be checked, particularly if bleeding is suspected.
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 cases of severe intoxication, as 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:
| Manifestations and symptoms | Test results | Therapeutic measures |
| Mild or moderate intoxication | | Gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis |
| Tachypnea, hyperventilation, respiratory alkalosis | Alkalemia, alkaluria | Restoration of electrolyte and acid-base balance |
| Diaphoresis (increased sweating) | | |
| Nausea, vomiting | | |
| Moderate or severe intoxication | | Gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, hemodialysis in severe cases |
| Respiratory alkalosis with compensatory metabolic acidosis | Acidemia, aciduria | Restoration of electrolyte and acid-base balance |
| Hyperpyrexia | | Restoration of electrolyte and acid-base balance |
| Respiratory: hyperventilation, noncardiogenic pulmonary edema, respiratory failure, asphyxia | | |
| Cardiovascular: dysarrhythmias, hypotension, cardiovascular failure | Changes in blood pressure, ECG | |
| Fluid and electrolyte loss: dehydration, oliguria, renal failure | Hypokalemia, hypernatremia, hyponatremia, changes in renal function | Restoration of electrolyte and acid-base balance |
| Glucose metabolism disorders, ketoacidosis | Hyperglycemia, hypoglycemia (especially in children). Elevated ketone bodies | |
| Ringing in the ears, deafness | | |
| Gastrointestinal: gastrointestinal (GI) bleeding | | |
| Hematologic: platelet inhibition, coagulopathy | PT prolongation, hypoprothrombinemia | |
| Neurological: toxic encephalopathy and central nervous system (CNS) depression with manifestations such as lethargy, confusion, coma, and seizures | | |
Side effects
On the part of the gastrointestinal system: frequent signs and symptoms of dyspepsia, nausea, vomiting, epigastric pain and abdominal pain; in some cases - inflammation of the gastrointestinal tract, erosive-ulcerative lesions of the gastrointestinal tract, which in isolated cases can cause gastrointestinal hemorrhages and perforations with corresponding laboratory indicators and clinical manifestations.
Blood and lymphatic system disorders: Due to its antiplatelet effect on platelets, acetylsalicylic acid may be associated with the development of bleeding, prolongation of bleeding time. Bleeding such as perioperative hemorrhages, hematomas, bleeding from the genitourinary system, epistaxis, bleeding from the gums have been observed; rarely or very rarely, serious bleeding such as gastrointestinal hemorrhages, cerebral hemorrhages (especially in patients with uncontrolled hypertension and/or concomitant use of antihemostatic agents), which in isolated cases could be potentially life-threatening.
Hemolysis and hemolytic anemia have been observed in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Thrombocytopenia, agranulocytosis, pancytopenia, leukopenia, aplastic anemia.
Renal and urinary disorders: renal dysfunction and development of acute renal failure.
Hepatobiliary disorders: Very rare reports of transient hepatic failure with increased serum transaminases and alkaline phosphatase.
Immune system disorders: asthma; hypersensitivity reactions such as erythematous/eczematous skin reactions, urticaria, rhinitis, nasal congestion, bronchospasm, angioedema, drop in blood pressure to the point of shock; severe skin reactions including exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Nervous system: headache, dizziness; confusion and tinnitus may indicate overdose.
Metabolism and nutrition disorders: hypoglycemia, acid-base imbalance.
From the reproductive system: menorrhagia.
Hypersensitivity reactions with appropriate laboratory and clinical manifestations, including asthmatic status, mild to moderate skin reactions, as well as reactions from the respiratory tract, gastrointestinal tract and cardiovascular system, including symptoms such as rash, urticaria, edema, itching, rhinitis, nasal congestion, cardiorespiratory failure and very rarely - severe reactions, including anaphylactic shock.
Others: Reye's syndrome (see section "Special warnings and precautions for use").
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
10 tablets in a blister; 10 blisters in a pack.
Vacation category
Without a prescription - 30 tablets.
According to the prescription - 100 tablets.
Producer
JSC "KYIV VITAMIN FACTORY".
Location of the manufacturer and address of its place of business
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua
