Composition, form of production and packaging
? Tablets covered with enteric-coated shell of white or almost white color, round, biconvex; on the cross-section - one layer of white or almost white color.
1 tab.
Acetylsalicylic acid 50 mg
Excipients: povidone low molecular weight - 3.3 mg, corn starch - 17 mg, microcrystalline cellulose - 10 mg, magnesium stearate - 1 mg, talc - 3 mg, lactose monohydrate - up to 95 mg.
Ingredients of enteric coating: 4 mg of cellase, 0.5 mg of titanium dioxide, 0.5 mg of castor oil.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
? Tablets covered with enteric-coated shell of white or almost white color, round, biconvex; on the cross-section - one layer of white or almost white color.
1 tab.
Acetylsalicylic acid 100 mg
Excipients: povidone low molecular weight - 6.6 mg, corn starch - 34 mg, microcrystalline cellulose - 20 mg, magnesium stearate - 2 mg, talc - 6 mg, lactose monohydrate - up to 190 mg.
Ingredients of enteric coating: cellacephate - 8 mg, titanium dioxide - 1 mg, castor oil - 1 mg.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
? Tablets covered with enteric-coated shell of white or almost white color, round, biconvex; on the cross-section - one layer of white or almost white color.
1 tab.
acetylsalicylic acid 300 mg
Excipients: povidone low molecular weight - 19.8 mg, corn starch - 102 mg, microcrystalline cellulose - 60 mg, magnesium stearate - 6 mg, talcum - 18 mg, lactose monohydrate - up to 570 mg.
Ingredients of the enteric coating: 24 mg of cellase, 3 mg of titanium dioxide, 3 mg of castor oil.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
The mechanism of antiplatelet action of acetylsalicylic acid (ASA) is irreversible inhibition of cyclooxygenase (COX-1), which blocks the synthesis of thromboxane A 2 and inhibits platelet aggregation. Antiaggregant effect develops even after application of small doses of the drug and persists for 7 days after a single dose. It is believed that ASA has other mechanisms for suppressing platelet aggregation.
In high doses ASA (over 300 mg / day) also has anti-inflammatory, antipyretic and analgesic effects.
PHARMACOKINETICS
Suction
After oral administration ASA is quickly and completely absorbed from the digestive tract. ASA is partially metabolized during absorption. During and after absorption, ASA converts to a major metabolite, salicylic acid, which is metabolized mainly in the liver under the influence of enzymes to form metabolites such as phenyl salicylate, salicylic acid glucuronide and salicyluric acid found in many tissues and in urine. In women, the metabolic process is slower (less enzyme activity in the blood serum).
C max ASA in blood plasma is achieved after 10-20 minutes after ingestion, C max of salicylic acid - after 0.3-2 h.
Due to the fact that the tablets are covered with an acid-resistant coating, ASA is not released in the stomach (the membrane effectively blocks the dissolution of the drug in the stomach), but in the alkaline medium of the duodenum. Thus, the absorption of ASA in the form of enteric coated tablets is delayed by 3 to 6 hours compared to conventional tablets (without such a coating).
Distribution
ASA and salicylic acid bind to blood plasma proteins (from 66% to 98% depending on the dose) and are quickly distributed in the body. Salicylic acid penetrates the placenta and into breast milk.
Excretion
Elimination of salicylic acid is dose-dependent, since its metabolism is limited by the possibilities of the enzymatic system. T 1/2 is from 2-3 hours when using ASA in low doses and up to 15 hours when the drug is used in high doses (the usual dose of ASA as an analgesic and antipyretic agent). Unlike other salicylates, with repeated administration of the drug, unhydrolyzed ASA does not accumulate in the blood serum. Salicylic acid and its metabolites are excreted by the kidneys. In patients with normal kidney function 80-100% of a single dose of the drug is excreted by the kidneys within 24-72 hours.
INDICATIONS
- prevention of acute myocardial infarction in the presence of risk factors (for example, diabetes mellitus, hyperlipidemia, arterial hypertension, obesity, smoking, old age);
- prevention of repeated myocardial infarction;
- unstable angina;
- prevention of ischemic stroke (including in patients with transient impairment of cerebral circulation);
- prevention of thromboembolism after surgery and invasive vascular interventions (eg, coronary artery bypass grafting, carotid endarterectomy, arteriovenous shunting, angioplasty and stenting of the coronary arteries, carotid angioplasty);
- Prevention of deep vein thrombosis and thromboembolism of the pulmonary artery and its branches (including with prolonged immobilization as a result of extensive surgical intervention).
DOSING MODE
Tablets should be taken before meals, washed down with a large amount of liquid, 1 time / day. Acecardol В® is intended for long-term use. The duration of therapy is determined by the doctor.
Prevention for suspected acute myocardial infarction: 100 mg / day daily or 300 mg every other day (the first tablet must be chewed for faster absorption).
Prevention of the first acute acute myocardial infarction in the presence of risk factors: 100 mg / day daily or 300 mg every other day.
Prevention of repeated myocardial infarction and unstable angina: 100-300 mg / day daily.
Prophylaxis of ischemic stroke and transient impairment of cerebral circulation: 100-300 mg / day daily.
Prevention of thromboembolism after surgery and invasive vascular interventions: 100-300 mg / day daily.
Prevention of deep vein thrombosis and thromboembolism of the pulmonary artery and its branches: 100 mg / day or 300 mg every other day.
SIDE EFFECT
On the part of the digestive system: nausea, heartburn, vomiting, abdominal pain; ulcers of the mucous membrane of the stomach and duodenum; perforated ulcers of the stomach and duodenum, gastrointestinal bleeding, transient violations of liver function with increased activity of hepatic transaminases.
On the part of the hemopoietic system: the appointment of ASA is accompanied by an increased risk of bleeding due to the inhibitory effect of ASA on platelet aggregation, anemia.
Allergic reactions: skin rash, itchy skin, urticaria, Quincke's edema, rhinitis, nasal mucosa edema, cardiorespiratory distress syndrome, and severe reactions, including anaphylactic shock.
From the respiratory system: bronchospasm.
From the side of the central nervous system: dizziness, hearing loss, headache, tinnitus.
CONTRAINDICATIONS
- erosive-ulcerative lesions of the gastrointestinal tract (in the phase of exacerbation);
- gastrointestinal hemorrhage;
- hemorrhagic diathesis;
- bronchial asthma induced by the intake of salicylates, a complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and ASA intolerance;
- marked renal failure (creatinine clearance (CK) less than 30 ml / min);
- marked hepatic insufficiency (class B and C on the Child-Pugh scale);
- Chronic heart failure (III-IV functional class according to the NYHA classification);
- simultaneous reception of methotrexate in a dose of 15 mg / week or more;
- I and III trimesters of pregnancy;
- lactation period;
- children's age till 18 years;
- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
- Hypersensitivity to ASA.
With caution when :
- gout, hyperuricemia, t.p. ASA in low doses reduces the excretion of uric acid; it should be borne in mind that ASA in low doses can provoke the development of gout in predisposing patients (having decreased urinary acid excretion);
- peptic ulcer of stomach and duodenum or gastrointestinal bleeding (in anamnesis);
- impaired liver function (class A on the Child-Pugh scale);
- impaired renal function (QC more than 30 ml / min);
- bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis, drug allergy;
- concomitant use of methotrexate in a dose of less than 15 mg / week;
- concomitant therapy with anticoagulants;
- II trimester of pregnancy;
- the proposed surgical intervention (including small, for example, extraction of the tooth); ASA can cause a tendency to develop bleeding within a few days after taking the drug.
PREGNANCY AND LACTATION
The use of salicylates in large doses in the first 3 months of pregnancy is associated with an increased frequency of fetal development defects (split sky, heart defects). The appointment of salicylates in the first trimester of pregnancy is contraindicated.
In the second trimester of pregnancy, salicylates can be given only with a strict risk assessment for the fetus and benefit to the mother, preferably at doses not exceeding 150 mg / day and for a short time.
In the third trimester of pregnancy, high-dose salicylates (more than 300 mg / day) cause weakening of labor, premature closure of the arterial duct in the fetus, increased bleeding in the mother and fetus, and the appointment immediately before childbirth can cause intracranial hemorrhages, especially in premature infants.The appointment of salicylates in the III trimester of pregnancy is contraindicated.
Salicylates and their metabolites penetrate into breast milk in small amounts, so breastfeeding should be abolished during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in severe renal failure (creatinine clearance (CK) less than 30 ml / min).
With caution in the violation of kidney function (QC more than 30 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in severe hepatic insufficiency (class B and C on the Child-Pugh scale).
With caution in the violation of liver function (class A on the scale Child-Pugh).
APPLICATION FOR CHILDREN
Contraindication: age to 18 years.
SPECIAL INSTRUCTIONS
ASA can provoke bronchospasm, as well as cause seizures of bronchial asthma and other reactions of hypersensitivity. Risk factors are the presence of bronchial asthma in history, hay fever, nasal polyposis, chronic diseases of the respiratory system, as well as allergic reactions to other drugs (eg, skin reactions, pruritus, urticaria).
The inhibitory effect of ASA on platelet aggregation persists for several days after admission, which may increase the risk of bleeding during surgery or in the postoperative period. If absolute elimination of bleeding is necessary in the course of surgical intervention, it is necessary, if possible, to completely abandon the use of ASA in the preoperative period.
ASA in low doses can provoke the development of gout in predisposed individuals (having a decreased excretion of uric acid).
When combined use of GCS and salicylates should be remembered that during treatment, the concentration of salicylates in the blood is reduced, and after the abolition of SCS, an overdose of salicylates is possible.
Excess dose of ASA is associated with a risk of gastrointestinal bleeding.
Impact on the ability to drive vehicles and manage mechanisms
Caution should be exercised when administering Accekardol В® when controlling vehicles, mechanisms and other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Overdose is unlikely because of the low content of ASA in the drug. Excess dose of ASA is associated with a risk of gastrointestinal bleeding. Overdose is especially dangerous in elderly patients.
Symptoms of an overdose from mild to moderate severity: dizziness, tinnitus, hearing impairment, increased sweating (including profuse), nausea, vomiting, headache, confusion, tachypnea, hyperventilation, respiratory alkalosis.
Treatment: gastric lavage, repeated intake of activated carbon, forced alkaline diuresis, restoration of water-electrolyte balance and acid-base state.
Symptoms of an overdose from medium to severe:
- respiratory alkalosis with compensatory metabolic acidosis;
- hyperpyrexia (extremely high body temperature);
- breathing disorders: hyperventilation, non-cardiogenic pulmonary edema, respiratory depression, asphyxia;
- cardiovascular system disorders: heart rhythm disturbances, decreased blood pressure, depression of cardiac activity;
- Violations of the water-electrolyte balance: dehydration, impaired renal function from oliguria up to the development of renal failure, characterized by hypokalemia, hypernatremia, hyponatremia;
- a violation of glucose metabolism: hyperglycemia, hypoglycemia (especially in children), ketoacidosis;
- noise in the ears, deafness;
- gastrointestinal bleeding;
- hematological disorders: from inhibition of platelet aggregation to coagulopathy, prolongation of prothrombin time, hypoprothrombinemia;
- neurological disorders: toxic encephalopathy and depression of CNS function (drowsiness, confusion, coma, convulsions).
Treatment: immediate hospitalization in specialized departments for emergency therapy - gastric lavage, repeated intake of activated carbon, forced alkaline diuresis, hemodialysis, restoration of water-electrolyte balance and acid-base state, symptomatic therapy. When carrying out alkaline diuresis, it is necessary to achieve pH values ​​between 7.5 and 8. The forced alkaline diuresis should be performed when the concentration of salicylates in the plasma is more than 500 mg / L (3.6 mmol / L) in adults and 300 mg / L (2.2 mmol / L) in children.
DRUG INTERACTION
ASA, when used simultaneously, enhances the effect of the following drugs:
- Methotrexate by reducing renal clearance and displacing it from the bond with plasma proteins; Also, the combination of acetylsalicylic acid with methotrexate is accompanied by an increased incidence of side effects from the hematopoiesis;
- heparin and indirect anticoagulants due to disruption of platelet function and displacement of indirect anticoagulants from the connection with plasma proteins;
- thrombolytic agents and antiplatelet agents;
- Digoxin due to a decrease in its renal excretion;
- hypoglycemic agents (insulin and sulfonylurea derivatives) due to hypoglycemic properties of ASA itself in high doses and displacement of sulfonylurea derivatives from the connection with plasma proteins;
- Valproic acid due to its displacement from the bond with plasma proteins.
The combination of ASA with anticoagulants, thrombolytics and antiaggregants is accompanied by an increased risk of bleeding.
With the simultaneous reception of ASA with alcohol, there is an increase in the toxic effect of alcohol on the central nervous system, increasing the risk of damage to the mucous membrane of the gastrointestinal tract and prolonging the time of bleeding.
ASC at simultaneous use weakens the effect of the following drugs:
- uricosuric drugs - benzbromarone (reduction of uricosuric effect due to competitive suppression of renal tubular excretion of uric acid);
- ACE inhibitors (a dose-dependent decrease in the glomerular filtration rate due to inhibition of prostaglandins with vasodilating action is observed, and accordingly, weakening of hypotensive action is observed);
- Diuretics (when combined with ASA in high doses, there is a decrease in the glomerular filtration rate as a result of a decrease in the synthesis of prostaglandins in the kidneys).
By enhancing the elimination of salicylates, systemic GCSs weaken their action.
TERMS OF RELEASE FROM PHARMACY
The drug is approved for use as a means of OTC.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 3 years.
