Aspirin Cardio (Acetylsalicylic acid) tablets

The composition and form of issue:

Tablets, film-coated, soluble in the intestine.

active substance: 

acetylsalicylic acid 100 mg

300 mg

excipients: cellulose powder 10 or 30 mg corn starch 10 or 30 mg 

composition of shell: copolymer of methacrylic acid and ethacrylate 1:1 (Eudragit L30D) — 7,857 or 27, 709 mg of Polysorbate 80 — 0,186 or to 0.514 mg of sodium lauryl — or 0.157 inch 0,057 mg talc is 8.1 or 22,38 mg triethylcitrate — 0.8 mm or of 2.24 mg 

blistere in 10 PCs or 14 PCs. in cardboard pack 2, or 4 blisters.

Description pharmaceutical form:

Round, biconvex tablets of white color in cross section, is a homogeneous mass of white color, with a shell of the same color.

Pharmacokinetics:

After intake of acetylsalicylic acid (ASA) is rapidly and completely absorbed from the gastrointestinal tract. Ask partly metabolized during absorption. During and after absorption of ask becomes the major metabolite is salicylic acid, which is metabolized mainly in the liver under the influence of enzymes with the formation of metabolites such as phenyl salicylate, salicylate glucuronide and salitsilovaya acid, found in many tissues and urine. In women the metabolism process is slower (less enzyme activity in the blood serum). Cmax of ASA in the blood plasma is reached in 10-20 minutes after ingestion, salicylic acid — using about 0.3–2 h. Due to the fact that the tablets coated with an acid resistant shell, ask released not in the stomach (shell effectively blocks the dissolution of the drug in the stomach), and in the alkaline environment of the duodenum. Thus, the absorption of ASA in the form of tablets, enteric coated, delayed by 3-6 hours compared to conventional (without shell) tablets.

ASA and salicylic acid strongly bind to proteins of blood plasma (from 66 to 98%, depending on the dose) and rapidly distributed in the body. Salicylic acid crosses the placenta and is excreted in breast milk.

Deducing of salicylic acid is dose-dependent, since its metabolism is restricted by the enzyme system. T1/2 is 2-3 h with the use of ASA in low doses and up to 15 hours when using the drug in high doses (usual dose of ASA as analgesic). Unlike other salicylates, with multiple drug digitalisierung ask does not accumulate in the serum. Salicylic acid and its metabolites are excreted by the kidneys. In patients with normal renal function of 80-100% of a single dose of the drug is excreted by the kidneys within 24-72 hours

Description pharmacological action:

The mechanism of antiaggregatory action ask’s irreversible inhibition of COX-1, resulting in blocked synthesis of thromboxane A2 and inhibits the aggregation of platelets. Antiaggregatory effect is most pronounced in the platelets because they are not able to re-synthesize COX. It is believed that the ASC has other mechanisms of suppression of platelet aggregation, that broadens the area of its application in various vascular diseases.

ASA also has anti-inflammatory, analgesic and antipyretic effect.

Indications:

• primary prevention of acute myocardial infarction in the presence of risk factors (e.g. diabetes, hyperlipidemia, hypertension, obesity, Smoking, old age) and re-myocardial infarction
• unstable angina (including suspected acute myocardial infarction) and stable angina
• prevention of stroke (including patients with transient disorders of cerebral circulation)
• prevention of transient disorders of cerebral circulation
• prevention of thromboembolism after surgery and invasive procedures on vessels (for example coronary artery bypass grafting, endarterectomy of the carotid arteries, arteriovenous bypass grafting, angioplasty and stenting of the coronary arteries, angioplasty of carotid arteries)
• prevention of deep vein thrombosis and thromboembolism pulmonary artery and its branches (including during prolonged immobilization as a result of extensive surgery).

Contraindications:

• hypersensitivity to ASA, auxiliary substances of the drug and other NSAIDs
• bronchial asthma induced by ingestion of salicylates and NSAIDs, aspirin triad (combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of ASA)
• erosivno-azwenne shock syndrome (in the acute stage), gastrointestinal bleeding
• hemorrhagic diathesis
• combined use with methotrexate dose 15 mg per week or more
• pregnancy (I and III trimester)
• breastfeeding
• childhood and adolescence (up to 18 years)
• expressed kidney failure (Cl creatinine <30 ml/min)
• severe hepatic insufficiency (class and above of child-Pugh)
• chronic heart failure III–IV functional class NYHA classification.

WITH CAUTION

The following diseases and conditions:

gout hyperuricemia (because of ASA in low doses reduces the excretion of uric acid should be kept in mind that the ASA in low doses can trigger the development of gout in predisposed patients, with reduced excretion of uric acid)

a history of ulcers or gastrointestinal bleeding

violation of the liver (below the class according To child-Pugh)

violation of kidney function (Cl creatinine >30 ml/min), and circulatory disorders caused by atherosclerosis of renal arteries, congestive heart failure, hypovolemia, extensive surgical interventions, sepsis, cases of massive bleeding, as in all these cases, the ASA may increase the risk of acute renal failure and renal dysfunction

bronchial asthma, chronic respiratory diseases, hay fever, nasal polyposis, drug Allergy, including preparations of NSAIDs (analgesics, anti-inflammatory, Antirheumatic agents)

II trimester of pregnancy

in advance of surgery (including minor, for example, extraction of the tooth), as ASA may cause the tendency to develop bleeding for several days after taking the drug

interactions with the following drugs (see “Interactions”): methotrexate at a dose less than 15 mg per week of anticoagulant, thrombolytic or antiplatelet means of NSAIDs and derivatives of salicylic acid in large doses, digoxin hypoglycemic agents for oral administration (derivatives of sulfonyl-urea) and insulin valproic acid alcohol (alcoholic beverages in particular) are selective inhibitors of serotonin reuptake ibuprofen.

Application of pregnancy and breast-feeding:

Inhibition of PG synthesis may have a negative impact on pregnancy and the development of the embryo or fetus.

In the first trimester of pregnancy the use of large doses of salicylates (more than 300 mg/day we are talking about doses of ASA 500 mg as analgesic) is associated with increased incidence of defects of fetus development (cleft palate, heart defects). The appointment of salicylates in the first trimester of pregnancy is contraindicated.

In the second trimester of pregnancy salicylates can be assigned only subject to the rigorous assessment of risks and benefits to mother and fetus preferably in doses no higher than 150 mg/day and short.

In the third trimester of pregnancy salicylates in high doses (over 300 mg/day we are talking about doses of ASA 500 mg as analgesic) can cause inhibition of labor, premature closure of the ductus arteriosus in the fetus, increased bleeding in the mother and fetus, and the appointment immediately before childbirth can cause intracranial hemorrhages, especially in preterm infants. The appointment of salicylates in the third trimester of pregnancy is contraindicated.

Use during lactation. Salicylates and their metabolites in small amounts of infiltrating breast milk. Casual reception salicylates during lactation is not accompanied by the development of adverse reactions in children and do not require discontinuation of breastfeeding. However, prolonged use of the drug or appoint him to a high dose breast-feeding should be discontinued immediately.

Side effects:

From the digestive system: the most frequent are nausea, heartburn, vomiting, abdominal pain, rarely ulcers of the gastric mucosa and duodenal ulcers very rare — perforated ulcer of the gastric mucosa and duodenal ulcers, gastrointestinal bleeding (with clinical symptoms and laboratory changes), transient hepatic impairment with increase in liver transaminases.

With the hematopoietic system: the purpose of the ASC is accompanied by an increased risk of bleeding due to its inhibitory action on platelet aggregation. Registered increase in the incidence of perioperative (intra – and postoperative) bleeding, hematomas (bruises), bleeding nose, bleeding gums, bleeding from the urinary tract. There are reports of serious cases of bleeding, which include gastrointestinal bleeding and brain hemorrhage (especially in patients with hypertension who have not reached target blood pressure and/or receiving concomitant therapy with anticoagulant drugs), which in some cases can carry life-threatening nature (see the “Special instructions”).

Bleeding can lead to acute or chronic post-hemorrhagic/iron deficiency anemia (for example due to hidden bleeding) with relevant clinical and laboratory signs and symptoms (asthenia, pallor, hypoperfusion).

There are reported cases of hemolysis and hemolytic anemia in patients with severe deficiency of glucose-6-phosphate dehydrogenase.

Allergic reactions: possible hypersensitivity reactions with respective laboratory and clinical manifestations, such as asthmatic symptoms (bronchospasm), reactions of mild to moderate severity on the part of the skin, respiratory tract, gastrointestinal tract and cardiovascular system, including symptoms such as skin rash, pruritus, urticaria, angioedema, edema of the nasal mucosa, rhinitis, cardio-respiratory distress syndrome, and severe reactions, including anaphylactic shock.

CNS: there are reports of cases of dizziness, hearing loss, headache, tinnitus that can be a sign of drug overdose (see “Overdose”).

From the urinary system: there are reports of cases of development of renal dysfunction and acute renal failure.

Drug interactions:

While the use of ASA increases the effects of the following drugs with the simultaneous appointment of ask with the listed tools should consider the need to reduce the dose of these drugs:

– methotrexate is by reducing renal clearance and ousting him from the protein due to the combination of ASA and methotrexate is accompanied by increased incidence of side effects from the blood the drug Aspirin Cardio in conjunction with methotrexate is contraindicated if the last dose exceeds 15 mg per week (see “Contraindications”), and perhaps with caution — the dose of methotrexate less than 15 mg per week

– heparin and indirect anticoagulants — due to dysfunction of platelets, and displacement of anticoagulants from the blood while the use of anticoagulants, thrombolytic and antiplatelet drugs (tiklopidin) there is an increase risk of bleeding as a result of the synergy of the main therapeutic effects of the drugs and strengthening of the damaging effect on the gastrointestinal mucosa

selective inhibitors of serotonin reuptake, because it may increase the risk of bleeding from the upper gastrointestinal tract (synergy with ASA)

– digoxin — by reducing its renal excretion, which can lead to overdose

– hypoglycemic agent for oral administration (derived sulfonylureas) and insulin — due to the hypoglycemic properties of the ASA in high doses and displacement derived sulfonylureas from plasma proteins of blood is necessary to keep in mind in the appointment of ask patients with diabetes who receive these drugs

– concomitant use with valproic acid increases its toxicity due to displacement from plasma proteins blood

– NSAIDs, including derivatives of salicylic acid at high doses (increased risk of ulcerogenic effect and bleeding from the digestive tract as a result of synergistic action)

– ethanol (alcoholic beverages) (increased risk of injury of gastrointestinal mucosa and prolonged bleeding time due to cross-amplification effects of ASA and ethanol).

Co-administration of ASA in high doses can weaken the effect of the following drugs. If simultaneous assignment of ASA and listed drugs should consider the need for dose adjustment the following tools:

– any diuretics (combined with ASA in high doses there is a decrease in glomerular filtration rate due to the reduction of PG synthesis in the kidney)

– ACE inhibitors (marked dose-dependent decrease in glomerular filtration rate (GFR) as a result of inhibition of PG, which has vasodilating effect, and, consequently, the weakening of hypotensive action. The clinical significance of the reduced GFR observed at a daily dose of ASA of more than 160 mg. in addition, there is a decrease in positive cardioprotective actions of ACE inhibitors, assigned to patients for the treatment of chronic heart failure. This effect is also evident when used in conjunction with ASA in high doses)

– drugs with uricosuric action — benzbromarone, probenecid (decrease uricosuric effect due to competitive suppression of the renal tubular excretion of uric acid).

While the use of ibuprofen marked antagonism towards the irreversible inhibition of platelets, due to the action ask, which leads to a reduction in the cardioprotective effects of ASA. Therefore it is not recommended the combination of ASA and ibuprofen in patients with increased risk of cardiovascular disease.

While the use of systemic corticosteroids (except hydrocortisone or other corticosteroids used for replacement therapy Addison’s disease) there is an increased elimination of salicylates and, accordingly, the weakening of their actions. With the combined use of SCS and salicylates should remember that the level of salicylates in the blood is reduced, and after the abolition of the SCS is possible overdose of salicylates.

Method of application and dose:

Inside, before eating, squeezed more liquid. Aspirin Cardio designed for prolonged use. Tablets should be taken 1 time per day. The duration of therapy determined by the treating physician.

Primary prevention of acute myocardial infarction in the presence of risk factors — 100 mg/day or 300 mg a day.

Prevention of re-infarction, stable and unstable angina — 100-300 mg/day.

Unstable angina (in cases of suspected acute myocardial infarction) — initial dose of 100-300 mg (the first tablet should be chewed for faster absorption) should be taken by the patient as soon as possible after suspected acute myocardial infarction. In the next 30 days after myocardial infarction must be maintained at a dose of 200-300 mg/day. After 30 days, you should assign the appropriate therapy for the prevention of recurrent myocardial infarction.

The prevention of stroke and transient disorders of cerebral circulation is 100-300 mg/day.

Prevention of thromboembolism after surgery and invasive procedures on vessels — 100-300 mg/day.

Prevention of deep vein thrombosis and thromboembolism pulmonary artery and its branches: 100-200 mg/day or 300 mg a day.

Actions when skipping one or more doses of a medicinal product

You must take the missed pill as soon as the patient remembers about it, avoid doubling the dose to take the missed pill if priblijaetsa the time of admission the following.

Features of action of the drug upon first admission and withdrawal thereof. Features of the product at first use and its abolition was observed.

Overdose:

Salicylate intoxication (develops while taking ASA in a dose of 100 mg/kg/day for more than 2 days) may be the result of long-term use toxic doses of the drug within the incorrect therapeutic use (chronic intoxication) or a single accidental or intentional ingestion of toxic doses of drugs to adults or child (acute intoxication).

Symptoms of chronic intoxication derivatives of salicylic acid are nonspecific and are often diagnosed with difficulty. Intoxication mild usually develops only after repeated use of large doses of the drug and is manifested by dizziness, tinnitus, hearing loss, increased perspiration, nausea and vomiting, headache and confusion. The listed symptoms disappear after reducing the dose of the drug. Tinnitus may appear when the concentration of ASA in blood plasma from 150 to 300 µg/ml. More severe symptoms occur when the concentration of ASA in the blood plasma is above 300 µg/ml.

The main manifestation of acute intoxication is severe disturbance of acid-base status, the manifestations of which can vary depending on the patient’s age and severity of intoxication. In children, the most typical is the development of metabolic acidosis. Treatment of intoxication is conducted in accordance with accepted standards and depends on the severity of intoxication and clinical picture and should be focused primarily on the rapid elimination of the drug and restoration of water and electrolyte balance and acid-base status.

Overdose symptoms mild to moderate: dizziness, tinnitus, hearing loss, 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 fluid and electrolyte balance and acid-base status.

Overdose symptoms are moderate to severe: respiratory alkalosis with compensatory metabolic acidosis or hyperpyrexia (extremely high fever), respiratory disorders (hyperventilation, necardiogenny pulmonary edema, respiratory depression, apnea) disorders of the cardiovascular system (arrhythmia, hypotension, depression of cardiac activity) violation of water-electrolyte balance: dehydration, impaired renal function oliguria from until the development of renal failure, characterized by hypokalemia, hypernatremia, hyponatremia, the metabolic disorder of glucose (hyperglycemia, hypoglycemia (especially in children), ketoacidosis) tinnitus, deafness, gastrointestinal bleeding hematologic disorders (inhibition of platelet aggregation to coagulation, elongation, PV, hypoprothrombinemia) neurological disorders (toxic encephalopathy and Central nervous system depression (drowsiness, confusion, coma, convulsions).

Treatment: immediate hospitalization in specialized departments for carrying out emergency therapy — gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, hemodialysis, restoration of water and electrolyte balance and acid-base balance, symptomatic therapy.

Special instructions:

The drug should be used on prescription.

ASA may provoke bronchospasm and cause asthma attacks and other hypersensitivity reactions. Risk factors are the availability of bronchial asthma in history, hay fever, nasal polyposis, chronic respiratory diseases, and allergic reactions to other drugs (eg skin reactions, pruritus, urticaria).

The inhibitory effect of ASA on platelet aggregation persists for several days after intake, in connection with which may increase the risk of bleeding during surgery or in the postoperative period. If necessary, the absolute exclusion of bleeding during surgical intervention should be possible to completely abandon the use of ASA in the preoperative period.

Excess dose ASA is associated with risk of gastrointestinal bleeding.

Overdose is especially dangerous in elderly patients.

In severe forms of deficiency of glucose-6-phosphate dehydrogenase ASA may cause hemolysis and hemolytic anemia. Factors that can increase the risk of hemolysis and hemolytic anemia — fever, acute infection and high doses of the drug.

Effects on ability to drive/ moving mechanisms. The drug, Aspirinate does not affect the ability to drive/moving mechanisms.