CardiASC, 50 mg 30 pcs

Pharmacotherapeutic group:

A nonsteroidal anti-inflammatory drug (NSAID).

ATX code: B01AC06.

Pharmacological properties

Pharmacodynamics
. The mechanism of antiplatelet action of acetylsalicylic acid (ASA) is based on irreversible inhibition of cyclooxygenase (COX-1), resulting in blocked synthesis of thromboxane A2 and suppressed platelet aggregation. The antiplatelet effect develops even after a low dose of the drug and lasts for 7 days after a single dose. It is believed that ASA has other mechanisms of platelet aggregation inhibition, which expands the field of its use in various vascular diseases. At high doses, ASK also has anti-inflammatory, antipyretic and analgesic effects.

Pharmacokinetics

After oral administration, ASK is quickly and completely absorbed from the gastrointestinal tract (GIT). ASK is partially metabolized during absorption. During and after absorption ASA is converted to the main metabolite, salicylic acid, which is metabolized mainly in the liver under the influence of enzymes to form metabolites such as phenylsalicylate, salicylic acid glucuronide and salicyluric acid found in many tissues and in the urine. In women, the metabolic process is slower (less enzyme activity in serum). The maximum concentration of ASA in blood plasma is reached within 10-20 minutes after oral administration, and that of salicylic acid – within 0.3-2 hours.

Due to the fact that the tablets are covered with an acid-resistant coating, ASK is not released in the stomach (the coating effectively blocks dissolution of the drug in the stomach), but in the alkaline environment of the duodenum. Thus, absorption of Asc in the form of tablets coated with an enteric coating is delayed by 3-6 hours compared to conventional (without such a coating) tablets.

ASA and salicylic acid bind to plasma proteins (from 66% to 98% depending on the dose) and are rapidly distributed in the body. Salicylic acid passes through the placenta and into the breast milk.

The excretion of salicylic acid is dose-dependent, since its metabolism is limited by the enzymatic system. The elimination half-life ranges from 2-3 hours when ASA is used in low doses and up to 15 hours when the drug is used in high doses (common doses of acetylsalicylic acid as an analgesic).

In contrast to other salicylates, non-hydrolyzed ASA does not accumulate in the blood serum when taking the drug repeatedly. Salicylic acid and its metabolites are excreted by the kidneys. In patients with normal renal function 80-100% of a single dose of the drug is excreted by kidneys within 24-72 hours.

Indications

– Primary prevention of acute myocardial infarction in the presence of risk factors (eg, diabetes, hyperlipidemia, hypertension, obesity, smoking, old age) and recurrent myocardial infarction.

– Unstable angina (including suspected acute myocardial infarction) and stable angina.

– Prevention of ischemic stroke (including in patients with transient cerebral circulation disorder).

– Prevention of thromboembolism after operations and invasive vascular interventions (e.g., aortocoronary bypass, carotid endarterectomy, arteriovenous bypass, angioplasty and stenting of coronary arteries, carotid angioplasty).

Prevention of deep vein thrombosis and thromboembolism of the pulmonary artery and its branches (including in case of prolonged immobilization as a result of extensive surgical intervention).

Active ingredient

Composition

1 film-coated, enteric-coated tablet contains:

Active substances:

acetylsalicylic acid 50 mg and 100 mg;

Auxiliary substances:

Stearic acid,

Corn starch,

Lactose monohydrate (milk sugar),

hydrogenated castor oil,

povidone (plasdon K-90 or collidon 90 F),

polysorbate (tween-80),

microcrystalline cellulose;

Auxiliary substances for the production of enteric soluble film coating:

Methacrylic acid and ethyl acrylate copolymer (1:1) (collicut MAE 100P), macrogol and polyvinyl alcohol copolymer (collicut IR), copovidone (plasdon ES-630), triethylcitrate, talc, titanium dioxide.

How to take, the dosage

Tablets of CardIASC® should preferably be taken before meals with plenty of fluid. CardIASC® tablets are taken once a day. CardIASC® is intended for long-term use. The duration of therapy is determined by the physician.

Primary prevention of acute myocardial infarction in the presence of risk factors: 50-100 mg/day.

Prevention of recurrent myocardial infarction, stable and unstable angina pectoris: 50-100 mg/day.

Unstable angina (when acute myocardial infarction is suspected): 50-100 mg/day.

Prevention of ischemic stroke and transient impairment of cerebral circulation: 50-100 mg/day.

Prevention of thromboembolism after surgery and invasive vascular interventions: 50-100 mg/day.

Prevention of deep vein thrombosis and pulmonary artery and branch thromboembolism: 50-100 mg/day.

Interaction

CardiacC®, when used concomitantly, potentiates the effects of the following medications:

– methotrexate by reducing renal clearance and displacing it from binding to plasma proteins, also the combination of acetylsalicylic acid with methotrexate is accompanied by an increased frequency of side effects from the hematopoietic organs;

Heparin and indirect anticoagulants due to disruption of platelet function and displacement of indirect anticoagulants from plasma proteins;

– thrombolytics and antiplatelet agents (ticlopidine);

– digoxin due to decrease of its renal excretion;

– hypoglycemic agents (insulin and sulfonylurea derivatives) due to the hypoglycemic properties of acetylsalicylic acid itself at high doses and displacement of sulfonylurea derivatives from plasma proteins;

– valproic acid due to its displacement from plasma proteins’ binding.

The combination of acetylsalicylic acid with anticoagulants, thrombolytics and antiaggregants is accompanied by an increased risk of bleeding. When concomitant use of acetylsalicylic acid with alcohol an additive effect is observed and the risk of gastrointestinal mucosal damage and prolongation of bleeding time increases.

ACK attenuates the effect of uricosuric drugs – benzbromaron (decreased uricosuric effect due to competitive inhibition of renal tubular excretion of uric acid), angiotensin-converting enzyme (ACE) inhibitors (noted, dose-dependent decrease in glomerular filtration rate due to inhibition of prostaglandins, having a vasodilator effect, respectively, weakening of hypotensive effect), diuretics (when used together with ASA in high doses, a decrease in glomerular filtration rate is observed as a result of reduced synthesis of prostaglandins in the kidneys). By increasing the elimination of salicylates, systemic glucocorticosteroids (GCS) weaken their effects.

Special Instructions

ASA can provoke bronchospasm, as well as causing attacks of bronchial asthma and other hypersensitivity reactions. Risk factors include a history of bronchial asthma, hay fever, nasal polyposis, chronic respiratory disease, and allergic reactions to other medications (e.g., skin reactions, itching, urticaria).

The inhibitory effect of ASA on platelet aggregation persists for several days after administration, and therefore the risk of bleeding during surgery or in the postoperative period may increase. If it is necessary to absolutely exclude bleeding during surgical intervention (it is necessary to completely refuse ASA use during the preoperative period, if possible).

Acetylsalicylic acid in low doses may provoke the development of gout in predisposed persons (who have reduced excretion of uric acid). High doses of acetylsalicylic acid have a hypoglycemic effect, which should be kept in mind when prescribing it to patients with diabetes receiving hypoglycemic drugs.

When using GCS and salicylates in combination, we should remember that during treatment, the concentration of salicylates in blood is decreased, and after withdrawal of GCS, an overdose of salicylates is possible.

Exceeding the dose of acetylsalicylic acid is associated with the risk of gastrointestinal bleeding.

Contraindications

– Hypersensitivity to acetylsalicylic acid, excipients in the drug and other non-steroidal anti-inflammatory drugs (NSAIDs).
– Bronchial asthma induced by taking salicylates and other NSAIDs; complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, intolerance to ASA and other NSAIDs.
– Erosive-ulcerous lesions of the gastrointestinal tract (in the acute stage).
– Gastrointestinal bleeding.
– Hemorrhagic diathesis.
– Combined use with methotrexate at a dose of 15 mg per week or more.
– Pregnancy (I and III trimester) and lactation.
– Children under 18 years old.
– Severe renal insufficiency (creatinine clearance (CK) less than 30 ml/min).
– Severe hepatic insufficiency (class B or higher according to the Child-Pugh scale).
– Chronic heart failure (class III-IV functional class according to NYHA classification).
– Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution

– In gout, hyperuricemia, because ASA in low doses reduces uric acid excretion; it should be borne in mind that ASA in low doses may provoke the development of gout in predisposed patients (having decreased uric acid excretion).
– In the presence of a history of gastrointestinal ulcers or gastrointestinal bleeding.
– In case of liver function abnormality (below grade B of the Child-Pugh scale).
– In case of impaired renal function (CKG more than 30 ml/min).
– In bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis, drug allergies, including those of NSAID group (analgesics, anti-inflammatory and antirheumatic agents).
– In the 2nd trimester of pregnancy.
– In anticipated surgical interventions (including minor ones, such as tooth extraction), because ASA may cause a tendency to develop bleeding within a few days after taking the drug.

Side effects

Digestive system disorders: Most commonly nausea, heartburn, vomiting, abdominal pain; rarely – gastric and duodenal mucosa ulcers; very rarely – perforative gastric and duodenal mucosa ulcers, gastrointestinal bleeding, transient liver function disorders with increased activity of “liver” transaminases.

With the hematopoietic system: ASA administration is accompanied by an increased risk of bleeding due to the inhibitory effect of ASA on platelet aggregation, rarely – anemia.

Allergic reactions: skin rash, pruritus, urticaria, Quincke’s edema, rhinitis, nasal mucosal edema, rhinitis, cardiorespiratory distress syndrome, and severe reactions, including anaphylactic shock.

From the central nervous system:dizziness, decreased hearing, headache, tinnitus.

Overdose

Salicylate intoxication (developed when taking ASA at a dose of more than 100 mg/kg/day for more than 2 days) can result from long-term use of toxic doses of the drug in the context of misuse of the drug (chronic intoxication) or a single accidental or intentional administration of a toxic dose of the drug by an adult or child (acute intoxication).

The symptoms of chronic intoxication with salicylic acid derivatives are nonspecific and often difficult to diagnose. Mild intoxication usually develops only after repeated use of large doses of the drug and is manifested by dizziness, tinnitus, decreased hearing, increased sweating, nausea and vomiting, headache, and confusion. The above symptoms disappear after reducing the dose of the drug. Tinnitus may occur at blood plasma concentrations of ASA between 150 and 300 mcg/mL.

More severe symptoms occur at plasma ASA concentrations above 300 mcg/ml. The main manifestation of acute intoxication is a severe violation of acid-base status, manifestations of which may vary depending on the age of the patient and the severity of intoxication. In children, the most typical is the development of metabolic acidosis. The treatment of intoxication is carried out in accordance with accepted standards and depends on the severity of intoxication and clinical picture, and should be aimed mainly at acceleration of drug elimination and restoration of water-electrolyte balance and acid-base status.

Overdose is particularly dangerous in elderly patients.

The symptoms of overdose are mild to moderate:

Dizziness, tinnitus, impaired hearing, increased sweating, nausea, vomiting, headache, confusion, profuse sweating, tachypnea, hyperventilation, respiratory alkalosis.

Treatment: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, restoration of water-electrolyte balance and acid-base balance.

Symptoms of moderate to severe overdose:

– respiratory alkalosis with compensatory metabolic acidosis;
– hyperpyrexia (extremely high body temperature);
– respiratory disorders: hyperventilation, noncardiogenic pulmonary edema, respiratory depression, asphyxia;
– disorders of the cardiovascular system: cardiac rhythm disorders, decreased pressure, depressed cardiac activity;
– disorders of the water-electrolyte balance: dehydration (dehydration), disorders of renal function from oliguria up to development of renal failure, characterized by hypokalemia, hypernatriemia, hyponatriemia;
– disorders of glucose metabolism: hyperglycemia, hypoglycemia (especially in children), ketoacidosis;
– tinnitus, 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, seizures).

Treatment:

Immediate hospitalization in specialized departments for emergency therapy – gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, hemodialysis, restoration of water-electrolyte balance and acid-base state, symptomatic therapy.

Pregnancy use

The use of high doses of salicylates in the first 3 months of pregnancy is associated with an increased incidence of fetal defects (cleft palate, heart defects). Prescribing salicylates in the first trimester of pregnancy is contraindicated. In the second trimester of pregnancy salicylates may be administered only after a strict assessment of the risk to the fetus and the benefit to the mother, preferably in doses not exceeding 150 mg/day and for short periods of time.

In the last trimester of pregnancy, salicylates at high doses (over 300 mg/day) cause impaired labor, premature closure of the fetal arterial duct, increased bleeding in the mother and fetus, and administration just before delivery may cause intracranial hemorrhage, especially in premature infants. Prescribing salicylates in the last trimester of pregnancy is contraindicated.

Salicylates and their metabolites penetrate into breast milk in small amounts. Accidental intake of salicylates during lactation is not accompanied by the development of adverse reactions in the child and does not require discontinuation of breastfeeding. However, if the drug is used for a long time or if it is prescribed in a high dose, breastfeeding should be stopped immediately.

Similarities