Phasostabil, 150 mg+30.39 mg 50 pcs.

The mechanism of 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. It is believed that ASA has other mechanisms to inhibit platelet aggregation, which expands the field of its use in various vascular diseases. ASA also has anti-inflammatory, analgesic, and antipyretic effects. Its anti-inflammatory effect is related to decrease of blood flow due to inhibition of prostaglandin E2 synthesis.
Magnesium hydroxide contained in the preparation Fasostabil has an antacid effect and protects the mucous membrane of the gastrointestinal tract from ASA.
Pharmacokinetics
Absorption
After oral administration ASK is quickly and almost completely absorbed from the gastrointestinal tract. Simultaneous intake of food slows down absorption. Partially metabolized during absorption.
Distribution and metabolism
During and after absorption ASK is converted to the main metabolite – salicylic acid, which is metabolized under the influence of enzymes, mainly in the liver to form metabolites (phenylsalicylate, salicylate glucuronide and salicyluric acid) found in many tissues and body fluids. In women the metabolic process is slower (lower activity of enzymes in blood serum).
Maximal ASK concentration in blood plasma is reached in 10-20 minutes after oral intake, salicylic acid – in 0.3-2 hours. Asc and salicylic acid are highly bound to blood plasma proteins and rapidly distributed in the body. The degree of binding of salicylic acid to plasma proteins is concentration-dependent, not linear. At low concentrations (less than 100 µg/ml) up to 90% of salicylic acid is bound to blood plasma proteins, at high concentrations (more than 400 µg/ml) – up to 75%.
The bioavailability of ASA is 50-68%, salicylic acid – 80-100%. Salicylic acid penetrates the placental barrier and is found in breast milk.
In renal insufficiency, during pregnancy and in infants, salicylates may displace bilirubin from binding to albumin and contribute to bilirubin encephalopathy.
Excretion
ASK and its metabolites are excreted primarily by the kidneys.
The half-life of ASK is 15-20 minutes, salicylic acid is 2-3 hours when taking ASK in low doses and increases significantly when taking ASK in high doses as a result of enzyme system saturation. Unlike other salicylates, non-hydrolyzed ASA does not accumulate in blood serum when repeatedly administered. In patients with normal renal function 80-100% of a single dose of ASA is excreted by kidneys within 24-72 hours.
Magnesium hydroxide in administered doses does not affect the bioavailability of ASA.

Indications

Stenocardia, Heart failure, Prevention of heart attacks and strokes, Prevention of thrombosis

• Primary prevention of cardiovascular diseases such as thrombosis and acute heart failure in the presence of risk factors (eg, diabetes, hyperlipidemia, 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).
  

Active ingredient

Acetylsalicylic acid, Magnesium hydroxide

Composition

Active ingredients: acetylsalicylic acid – 150.00 mg; magnesium hydroxide – 30.39 mg.
Excipients (core): microcrystalline cellulose – 167.81 mg, croscarmellose sodium – 16.00 mg, povidon-K25 – 12.00 mg, magnesium stearate – 3.80 mg.
Excipients (coating): hypromellose – 4.80 mg, macrogol-4000 – 1.20 mg, titanium dioxide – 2.00 mg.

How to take, the dosage

Orally, film-coated tablets of the preparation Fasostabil should be swallowed whole with water.
The preparation Fasostabil is intended for long-term treatment.
Duration of treatment is determined by the doctor.
– Primary prophylaxis of cardiovascular diseases, such as thrombosis and acute heart insufficiency in presence of risk factors (for example, diabetes, hyperlipidemia, arterial hypertension, obesity, smoking, old age).
1 tablet of the preparation Fasostabil, containing ASA 150 mg during the first day and then 1 tablet with ASA 75 mg once a day.
– Prevention of recurrent myocardial infarction and blood vessel thrombosis
1 tablet of the preparation Fazostabil, containing ASK in the dosage of 75-150 mg once a day.
– Prophylaxis of thromboembolism after surgical interventions on the vessels (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty).
1 tablet of the preparation Fasostabil, containing ASA at a dose of 75-150 mg once a day.
– Unstable angina pectoris
1 tablet of the preparation Fasostabil containing ASA in the dosage of 75-150 mg once a day.
If the next dose of Fasostabil is missed, take the missed dose as soon as the patient remembers it. To avoid doubling the dose, do not take the missed tablet if the time of the next dose is approaching.
Peculiarities of action during the first administration or cancellation of the drug were not observed.

Interaction

• Concomitant use of ASA increases the effect and increases the risk of toxicity:
  – methotrexate (by reducing renal clearance and displacing it from binding to plasma proteins);
  – valproic acid (by displacing it from binding to plasma proteins);
• ASC increases the effect and increases the risk of adverse reactions:
  – narcotic analgesics, other non-steroidal anti-inflammatory drugs (due to synergistic effect)
  – oral hypoglycemic agents (sulfonylurea derivatives) and insulin due to hypoglycemic properties of ASA at high doses (more than 2 g per day) and displacing sulfonylurea derivatives from plasma proteins
  – thrombolytics, heparin, indirect anticoagulants (ticlopidine, warfarin), antiplatelet agents (including clopidogrel, dipyridamole) – due to synergism of main therapeutic effects and displacement of binding to plasma proteins;
  – sulphonamides, including co-trimoxazole – due to displacement from plasma protein binding and increased concentration in blood plasma;
  – carbohydrate inhibitors (acetazolamide). Concomitant use with ASA may lead to severe acidosis and increased toxic effect on the central nervous system;
  – Digoxin and lithium – due to decrease of renal excretion of digoxin and lithium with increase of their concentration in blood plasma;
  – selective serotonin reuptake inhibitors (including sertraline, paroxetine), which may increase the risk of bleeding from the upper gastrointestinal tract (synergism with ASA);
  – additive effect is observed when concomitant use of ASA with ethanol (alcohol): increased damage to the mucosa of the gastrointestinal tract and prolonged bleeding time (due to the additive effect of ethanol and ASA).
• Decrease the antiaggregant effect of ASA:
  – ibuprofen (due to antagonism to suppress platelet aggregation);
  – systemic glucocorticosteroids (except for hydrocortisone used for replacement therapy of Addison’s disease) (increase the elimination of salicylates);
  – Antacids containing aluminum and/or magnesium hydroxide, colestyramine (reduce absorption of ASA in the gastrointestinal tract);
• ASC at low doses attenuates the effects of uricosuric agents (benzbromaron, probenecid, sulfinpyrazone) due to competitive tubular elimination of uric acid.
  ASA in high doses, as well as other NSAIDs, may decrease antihypertensive effect of diuretics (due to decreased glomerular filtration rate due to inhibition of renal prostaglandin synthesis) and hypotensive agents. In particular, due to competitive blockade of prostacyclin synthesis, the effectiveness of angiotensin-converting enzyme inhibitors (ACE) may decrease.
  

Special Instructions

The drug should be used as prescribed by a doctor.
ASK may provoke bronchospasm, as well as cause attacks of bronchial asthma and other hypersensitivity reactions. Risk factors include a history of bronchial asthma, hay fever, nasal polyposis, chronic respiratory diseases, as well as allergic reactions to other drugs (e.g., skin reactions, itching, urticaria).
ASA can cause bleeding of varying severity during and after surgical interventions.
Several days before the planned surgical intervention, the risk of bleeding should be assessed compared to the risk of ischemic complications in patients taking low-dose ASA. If the risk of bleeding is significant, ASA administration should be temporarily stopped.
Concomitant use of ASA with anticoagulants, thrombolytics and antiplatelet agents is accompanied by an increased risk of bleeding.
In renal dysfunction (CK more than 30 ml/min), as well as in circulatory disorders due to atherosclerosis of the renal arteries, chronic heart failure, extensive surgery, sepsis, cases of massive bleeding, caution should be exercised because in all these cases ASA may increase the risk of acute renal failure/worsening of renal function (see section “Caution.
It is known that the risk of acute renal failure increases with coadministration of other NSAIDs with ACE inhibitors or diuretics.
In patients with mild to moderate hepatic impairment, liver function should be monitored regularly (see section “With caution”.)
ASK in low doses may provoke development of gout in predisposed patients (who have reduced excretion of uric acid).
Combination of ASK with methotrexate is accompanied by an increased frequency of side effects from the organs of hematopoiesis, concomitant use with valproic acid increases the risk of toxicity. During the first weeks of concomitant administration of Fazostabil and methotrexate in dose less than 15 mg weekly, a weekly blood test should be performed. Even with minor renal dysfunction and in elderly patients it is necessary to monitor carefully (see sect. “Contraindications”, “Caution”, “Interaction with other medicinal agents”).
Simultaneous administration of ASA with anticoagulants, thrombolytics and antiplatelet agents is associated with increased risk of bleeding and damaging effects on the mucosa of the gastrointestinal tract (see sections “Caution”, “Interaction with other medicinal products”). It is not recommended concomitant administration of Fazostabil and ibuprofen in patients with increased risk of cardio-vascular diseases, because the reduction of antiaggregant effect of ASA in doses up to 300 mg leads to the reduction of cardioprotective effect. Patients taking ibuprofen for pain relief should inform the physician about this (see sections “Caution”, “Interaction with other medicinal products”).
It is recommended to monitor plasma concentrations of digoxin and lithium at the beginning or at the end of concomitant administration of Fazostabil; dose adjustment may be required (see sect.
When concomitant use with diuretics and hypotensive agents (e.g. ACE inhibitors) the possible decrease of their effectiveness should be considered (see sect.
High doses of ASA have a hypoglycemic effect, which should be borne in mind when prescribing it to patients with diabetes mellitus receiving oral hypoglycemic agents and insulin.
When concomitant use of systemic glucocorticosteroids and salicylates, it should be remembered that during treatment the concentration of salicylates in blood is reduced, and after cancellation of systemic glucocorticosteroids, an overdose of salicylates is possible. With long-term use of low doses of ASA as anti-aggregant therapy it is necessary to be cautious in elderly patients due to the risk of gastrointestinal bleeding.
In long-term use of Fazostabil it is necessary to periodically control general blood count and fecal occult blood test as well as liver function tests.
Simultaneous administration of ASA with alcohol increases the risk of gastrointestinal mucosa damage and prolongation of bleeding time.
With severe forms of glucose-6 phosphate dehydrogenase deficiency ASA may cause hemolysis and hemolytic anemia (see section “Contraindications”). Factors that increase the risk of hemolysis and hemolytic anemia are fever, acute infections, and high doses of ASA.

Influence on driving and operating machinery

When treating with Fasostabil it is necessary to be careful when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reaction.

Contraindications

• High sensitivity to ASA, excipients of the drug and other nonsteroidal anti-inflammatory drugs (NSAIDs);
• Cerebral hemorrhage;
• Hypertension to bleeding (vitamin K deficiency, thrombocytopenia, hemorrhagic diathesis;
• Cronic cardiac insufficiency in the class of the drug.Bleeding tendency (vitamin K deficiency, thrombocytopenia, hemorrhagic diathesis);
• Cronic heart failure functional class III-IV by NYHA classification;
• Bronchial asthma induced by taking salicylates and NSAIDs;
• The complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to ASA or other NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors (including a history);
• Errotic ulcerative lesions of the gastrointestinal tract (acute phase);
• Gastrointestinal bleeding;
• Severe renal failure (creatinine clearance (CK) less than 30 ml/min.)
• Hepatic failure (Child-Pugh class B and C);
• Pregnancy (I and III trimesters), breastfeeding period;
• Deficiency in glucose-6-phosphate dehydrogenase;
• Simultaneous use with methotrexate (more than 15 mg per week);
• Children under 18 years of age.

Cautions

. In gout, hyperuricemia, history of gastrointestinal ulcers or gastrointestinal bleeding, mild to moderate renal failure (CK more than 30 ml/min), liver failure (class A according to the Child-Pugh classification), bronchial asthma, hay fever, nasal polyposis, allergic conditions, in II trimester of pregnancy, in diabetes, elderly age; concomitant use with the following medications: methotrexate (less than 15 mg weekly), anticoagulants, thrombolytics and antiaggregants, high-dose NSAIDs and salicylates, narcotic analgesics, sulfonamides (including co-trimoxazole), carboanhydrase inhibitors (acetazolamide), digoxin, lithium, oral hypoglycemic agents (sulfonylurea derivatives), insulin, valproic acid, selective serotonin reuptake inhibitors, ibuprofen, systemic glucocorticosteroids, ethanol (alcohol-containing drugs, drinks).

Side effects

Frequency of adverse reactions listed below, according to the classification of the World Health Organization, was determined according to the following: very common (≥1/10); common (>1/100, <1/10); infrequent (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000), including individual reports.
Immune system disorders: infrequent – urticaria, angioedema (Quincke’s edema), skin rash, itching, rhinitis, nasal mucous membrane edema; very rare – anaphylactic shock, cardio-respiratory distress syndrome.
Gastrointestinal tract: very common – heartburn; common – nausea, vomiting; infrequent – abdominal pain, gastric and duodenal mucosa ulcers, including perforative (rare), gastrointestinal bleeding; very rare – stomatitis, esophagitis, erosive lesions of upper gastrointestinal tract (including with strictures), colitis, irritable bowel syndrome.
Respiratory system, thorax and mediastinum: frequently – bronchospasm.
Blood and lymphatic system: very common – increased bleeding, rarely – anemia, very rare – aplastic anemia, hypoprothrombinemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, agranulocytosis.
There have been reports of hemolysis and hemolytic anemia in patients with severe forms of glucose-6-phosphate dehydrogenase deficiency.
Nervous system: frequently – headache, insomnia, infrequently – dizziness, somnolence, rarely – tinnitus, intracerebral hemorrhage.
Renal and urinary tract: very rare – renal dysfunction.
Effect on the results of laboratory and instrumental studies: rare – increased activity of “liver” enzymes.

Overdose

Salicyl syndrome develops when taking acetylsalicylic acid in a dose of more than 100 mg/kg/day for more than 2 days due to the use of toxic doses of the drug in the framework of improper therapeutic use (chronic poisoning) or a single accidental or intentional taking of a toxic dose of the drug by adult or child (acute poisoning).
Overdose is especially dangerous in elderly patients.
Symptoms of overdose in mild to moderate severity (single dose of less than 150 mg/kg):
Dizziness, tinnitus, hearing loss, increased sweating, nausea and vomiting, headache, confusion, tachypnea, hyperventilation, respiratory alkalosis.
Treatment: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, restoration of water-electrolyte balance and acid-base status.
Symptoms of overdose at moderate and severe degree of severity (single dose of 150 mg/kg – 300 mg/kg – moderate degree of severity, more than 300 mg/kg – severe degree of poisoning):
Respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, hyperventilation, noncardiogenic pulmonary edema, respiratory depression, asphyxia; cardiovascular system: heart rhythm disorder, marked BP reduction, cardiac suppression; water-electrolyte balance: dehydration, impaired renal function from oliguria up to development of renal failure, characterized by hypokalemia, hypernatriemia, hyponatremia; impaired 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 central nervous system function (drowsiness, confusion, coma, seizures).
Treatment: immediate hospitalization in specialized departments for emergency therapy – gastric lavage, repeated administration of activated charcoal, restoration of water-electrolyte balance and acid-base status, forced alkaline diuresis, symptomatic therapy.

Similarities

Cardiomagnil, Trombital, Trombital Forte