Fazostabil tablets 150 + 30.39mg, No. 100

• Primary prevention of cardiovascular diseases such as thrombosis and acute heart failure in the presence of risk factors (for example, diabetes mellitus, hyperlipidemia, arterial hypertension, obesity, smoking, old age);

• prevention of recurrent myocardial infarction and blood vessel thrombosis;

• prevention of thromboembolism after vascular surgery (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty);

• unstable angina.

Is taken orally, 1-2 hours after meals, 1 single dose 1 time / day. This combination is intended for long-term use. The duration of treatment is determined by the doctor.

No specific features of the drug's action at the first administration or withdrawal of the drug were observed.

Film-coated tablets

1 tab.

acetylsalicylic acid 150 mg

magnesium hydroxide 30.39 mg

Excipients: microcrystalline cellulose - 167.81 mg, croscarmellose sodium - 16 mg, povidone K25 - 12 mg, magnesium stearate - 3.8 mg.

• Hypersensitivity to acetylsalicylic acid, any of the excipients of the drug, other NSAIDs;

• bronchial asthma induced by the intake of salicylates and NSAIDs;

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs;

• erosive and ulcerative lesions of the gastrointestinal tract in the acute phase;

• gastrointestinal bleeding;

• hemorrhage in the brain; bleeding tendency (thrombocytopenia, hemorrhagic diathesis, vitamin K deficiency);

• severe renal failure (CC less than 30 ml / min);

• severe liver failure (more than 9 points on the Child-Pugh scale);

• I and III trimesters of pregnancy;

• lactation period;

• deficiency of glucose-6-phosphate dehydrogenase;

• simultaneous use with methotrexate (at a dose of 15 mg per week); age up to 18 years (efficacy and safety have not been established).

  Carefully

• Gout, hyperuricemia; a history of gastrointestinal ulcer or gastrointestinal bleeding; renal failure of mild to moderate severity (CC more than 30 ml / min) and / or liver failure (9 or less points on the Child-Pugh scale); bronchial asthma; chronic respiratory diseases; hay fever; polyposis of the nose and paranasal sinuses; allergic conditions; the period before surgery; simultaneous use with certain drugs (including methotrexate at a dose of <15 mg per week, valproic acid, anticoagulants, thrombolytic and antiplatelet agents, NSAIDs and acetylsalicylic acid derivatives in high doses, narcotic analgesics, sulfonamides / incl. co-trimoxazole /, carbonic anhydrase inhibitors / acetazolamide /, digoxin, lithium,oral hypoglycemic agents / sulfonylurea derivatives /, insulin, selective serotonin reuptake inhibitors, ibuprofen, GCS for systemic use); combined use with ethanol (ethanol-containing drugs, alcoholic beverages); II trimester of pregnancy.

pharmachologic effect

NSAIDs, antiplatelet agent.

The mechanism of action of acetylsalicylic acid is based on irreversible inhibition of the COX-1 enzyme, as a result of which the synthesis of thromboxane A2 is blocked and platelet aggregation is suppressed. It is believed that acetylsalicylic acid has other mechanisms for suppressing platelet aggregation, which expands the scope of its application in various vascular diseases. Acetylsalicylic acid also has anti-inflammatory, analgesic and antipyretic effects.

Magnesium hydroxide protects the gastrointestinal mucosa from the effects of acetylsalicylic acid.

Pharmacokinetics

After taking the drug inside, acetylsalicylic acid is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake slows down absorption. Acetylsalicylic acid is partially metabolized during absorption. The bioavailability of acetylsalicylic acid is about 70%, but this value is characterized by significant individual variability due to presystemic hydrolysis in the mucous membranes of the gastrointestinal tract and in the liver with the formation of salicylic acid under the action of enzymes. The bioavailability of salicylic acid is 80-100%.

Cmax of acetylsalicylic acid in blood plasma is achieved within 10-20 minutes after ingestion, salicylic acid - after 0.3-2 hours. Acetylsalicylic acid and salicylic acid are highly bound to blood plasma proteins and are quickly distributed in the body. The degree of binding of salicylic acid to blood plasma proteins depends on the concentration, not linear. At low concentrations (<100 ?g / ml), up to 90% of salicylic acid binds to blood plasma proteins, at high concentrations (> 400 ?g / ml) - up to 75%. Salicylic acid crosses the placental barrier and is found in breast milk.

Salicylic acid is metabolized by enzymes, mainly in the liver to form metabolites (phenyl salicylate, glucuronide salicylate and salicylic acid) found in many tissues and body fluids. In women, the metabolic process is slower (less enzyme activity in the blood serum).

Acetylsalicylic acid and its metabolites are excreted mainly by the kidneys. T1 / 2 of acetylsalicylic acid from blood plasma is 15-20 minutes, salicylic acid - 2-3 hours when taking acetylsalicylic acid in low doses and significantly increases when taking acetylsalicylic acid in high doses as a result of saturation of enzyme systems. Unlike other salicylates, with repeated administration of the drug, non-hydrolyzed acetylsalicylic acid does not accumulate in the blood serum. In patients with normal renal function, 80-100% of a single dose of acetylsalicylic acid is excreted by the kidneys within 24-72 hours.

In renal failure, during pregnancy and in newborns, salicylates can displace bilirubin from the association with albumin and contribute to the development of bilirubin encephalopathy.

Magnesium hydroxide in the doses used does not affect the bioavailability of acetylsalicylic acid.

Side effect

In general, preparations containing this combination are well tolerated.

From the nervous system: often - headache, insomnia; infrequently - dizziness, drowsiness; rarely - tinnitus, intracerebral hemorrhage.

From the side of the hematopoietic system: very often - increased bleeding; rarely - anemia; very rarely - aplastic anemia, hypoprothrombinemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, agranulocytosis. There are reports of cases of hemolysis and hemolytic anemia in patients with severe glucose-6-phosphate dehydrogenase deficiency.

From the respiratory system: often - bronchospasm.

From the digestive system: very often - heartburn; often - nausea, vomiting; infrequently - pain in the abdomen, ulcers of the mucous membrane of the stomach and duodenum, gastrointestinal bleeding; rarely - perforation of a stomach or duodenal ulcer, increased activity of liver enzymes; very rarely - stomatitis, esophagitis, erosive lesions of the upper gastrointestinal tract (including with strictures), colitis, irritable bowel syndrome.

Allergic reactions: infrequently - urticaria, Quincke's edema, skin rash, pruritus, rhinitis, swelling of the nasal mucosa; very rarely - anaphylactic shock, cardiorespiratory distress syndrome.

Others: very rarely - impaired renal function.

Application during pregnancy and lactation

The use of salicylates in high doses in the first trimester of pregnancy is associated with an increased incidence of fetal developmental defects (cleft palate, heart defects). Use in the first trimester of pregnancy is contraindicated. In the II trimester of pregnancy, it can be prescribed only taking into account a strict assessment of the ratio of the benefits of treatment to the mother and the potential risk to the fetus, in doses not exceeding 150 mg / day for a short time. In the third trimester of pregnancy, salicylates in a high dose (more than 300 mg / day) cause inhibition of labor, premature closure of the ductus arteriosus in the fetus, increased bleeding in the mother and fetus, and application immediately before childbirth can cause intracranial hemorrhage, especially in premature babies. Use in the third trimester of pregnancy is contraindicated.

Salicylates and their metabolites pass into breast milk in small amounts. There are insufficient clinical data to assess the safety of using acetylsalicylic acid during breastfeeding. Before prescribing acetylsalicylic acid during lactation, the expected benefits of therapy for the mother and the potential risk for infants should be assessed. Accidental intake of salicylates during lactation is not accompanied by the development of adverse reactions in the child and does not require termination of breastfeeding. However, if it is necessary to use this combination for a long time, breastfeeding should be stopped immediately.

Application for violations of liver function

The use of the drug is contraindicated in severe hepatic insufficiency (more than 9 points on the Child-Pugh scale).

The drug should be prescribed with caution in liver failure (9 or less points on the Child-Pugh scale).

Application for impaired renal function

The use of the drug is contraindicated in severe renal failure (CC less than 30 ml / min).

The drug should be prescribed with caution in case of renal failure of mild and moderate severity (CC more than 30 ml / min).

Application in children

The use of the drug under the age of 18 is contraindicated (efficacy and safety have not been established).

Use in elderly patients

Long-term use of acetylsalicylic acid in low doses in elderly patients is associated with an increased risk of gastrointestinal bleeding.

special instructions

Acetylsalicylic acid can provoke bronchospasm, as well as cause attacks of bronchial asthma and other hypersensitivity reactions. Risk factors include a history of bronchial asthma, hay fever, polyposis of the nose and paranasal sinuses, chronic diseases of the respiratory system, as well as allergic reactions (eg, skin reactions, itching, urticaria) to other drugs.

The inhibitory effect of acetylsalicylic acid on platelet aggregation persists for several days after administration, which should be taken into account during and after surgery. A few days before the planned surgery, the risk of bleeding should be assessed in comparison with the risk of ischemic complications in patients taking low-dose acetylsalicylic acid. With a significant risk of bleeding, the drug should be temporarily discontinued.

In case of impaired renal function (CC more than 30 ml / min), as well as circulatory disorders arising from atherosclerosis of the renal arteries, chronic heart failure, major surgery, sepsis, cases of massive bleeding, caution should be exercised, since in all of these cases, ASA can increase the risk of developing acute renal failure / deterioration of renal function. It is known that the risk of developing acute renal failure increases with the combined use of other NSAIDs with ACE inhibitors or diuretics. Monitoring of renal function is recommended.

In patients with mild to moderate hepatic impairment, liver function should be monitored regularly.

During the first weeks of combined use of the drug and methotrexate at a dose of less than 15 mg per week, a blood test should be performed weekly. Careful monitoring must be carried out in the presence of even minor renal dysfunctions, as well as in elderly patients.

With the combined use of acetylsalicylic acid with anticoagulants, thrombolytic and antiplatelet drugs, the risk of bleeding and damaging effects on the gastrointestinal mucosa increases, therefore bleeding time should be monitored.

Combined use with ibuprofen is not recommended in patients with an increased risk of cardiovascular diseases, since a decrease in the antiplatelet effect of acetylsalicylic acid in doses up to 300 mg leads to a decrease in cardioprotective effects. Patients taking ibuprofen for pain relief should inform their doctor.

It is recommended to monitor the concentration of digoxin and lithium in the blood plasma at the beginning or at the end of joint use with the combination of acetylsalicylic acid + magnesium hydroxide; dose adjustment may be required.

With the combined use of GCS for systemic use and acetylsalicylic acid, the concentration of salicylates in the blood plasma decreases, and after the abolition of GCS for systemic use, an overdose of salicylates is possible. In addition, when used together, the risk of damage to the gastrointestinal mucosa and bleeding increases.

The use of acetylsalicylic acid in doses exceeding the recommended therapeutic ones (by patients of any age), or long-term use of acetylsalicylic acid in low doses (by elderly patients) is associated with an increased risk of gastrointestinal bleeding. With prolonged use, you should periodically monitor a complete blood count and fecal occult blood test, as well as the functional state of the liver.

Acetylsalicylic acid in low doses reduces the excretion of uric acid and can provoke the development of gout in predisposed patients with decreased excretion of uric acid.

Acetylsalicylic acid in high doses has a hypoglycemic effect, which should be considered in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin.

In severe forms of glucose-6-phosphate dehydrogenase deficiency, acetylsalicylic acid can cause hemolysis and hemolytic anemia. Factors that increase the risk of hemolysis and hemolytic anemia are fever, acute infections, and high doses of acetylsalicylic acid.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment, care must be taken when driving vehicles and performing activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

When used together, acetylsalicylic acid enhances the effect and increases the risk of toxicity of the following drugs:

• methotrexate (due to a decrease in renal clearance and displacement from connection with blood plasma proteins);

• valproic acid (due to displacement from the connection with blood plasma proteins).

Acetylsalicylic acid enhances the effect and increases the risk of developing adverse reactions of the following drugs:

• narcotic analgesics, other NSAIDs (due to synergy of action);

• hypoglycemic agents for oral administration (sulfonylurea derivatives) and insulin (due to the hypoglycemic properties of acetylsalicylic acid itself in high doses (more than 2 g / day) and displacement of sulfonylurea derivatives from the connection with blood plasma proteins);

• thrombolytic drugs, heparin, indirect anticoagulants (including ticlopidine, warfarin), antiplatelet agents (including clopidogrel, dipyridamole) due to the synergism of the main therapeutic effects and displacement from the connection with blood plasma proteins;

• sulfonamides (including co-trimoxazole) due to displacement from the connection with blood plasma proteins and an increase in plasma concentration;

• carbonic anhydrase inhibitors (acetazolamide). Combined use with acetylsalicylic acid can lead to the development of severe acidosis and increased toxicity to the central nervous system;

• digoxin and lithium - by reducing the renal excretion of digoxin and lithium with an increase in their concentration in the blood plasma;

• selective serotonin reuptake inhibitors (including sertraline, paroxetine) - due to the synergistic action (with an increased risk of bleeding from the upper gastrointestinal tract).

• ethanol (alcohol and ethanol-containing drugs) - with an increase in the damaging effect on the gastrointestinal mucosa and an increased risk of gastrointestinal bleeding.

Reduce the antiplatelet effect of acetylsalicylic acid:

• ibuprofen (due to antagonism in suppressing platelet aggregation);

• GCS for systemic use (enhance the elimination of salicylates);

• antacids containing magnesium and / or aluminum hydroxide, cholestyramine (reduce the absorption of acetylsalicylic acid from the gastrointestinal tract).

Acetylsalicylic acid in low doses weakens the effect of uricosuric drugs (benzbromarone, probenecid, sulfinpyrazone) due to competitive suppression of renal tubular excretion of uric acid.

Acetylsalicylic acid in high doses, like other NSAIDs, can reduce the antihypertensive effect of diuretics (due to a decrease in the glomerular filtration rate due to suppression of renal prostaglandin synthesis) and antihypertensive drugs. In particular, due to the competitive blockade of prostacyclin synthesis, a decrease in the effectiveness of ACE inhibitors is possible.