Fazostabil - instructions for use, dose, side effects, contraindications

Active substanceAcetylsalicylic acid + Magnesium hydroxideAcetylsalicylic acid + Magnesium hydroxide

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Fazostabil

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ATOLL, LLC Russia

Dosage form: & nbspTfilm-covered abeys.

Composition:

For one tablet:

Dosage of 75.00 mg + 15.20 mg:

Active substances: Acetylsalicylic acid - 75.00 mg; magnesium hydroxide - 15,20 mg.

Excipients (core): cellulose microcrystalline - 83,90 mg, croscarmellose sodium - 8,00 mg, povidone-K25 - 6,00 mg, magnesium stearate - 1,90 mg.

Auxiliary substances (shell): hypromellose - 2.40 mg, macrogol-4000 - 0.60 mg, titanium dioxide - 1.00 mg.

Dosage of 150.00 mg + 30.39 mg

Active substances: Acetylsalicylic acid - 150.00 mg; magnesium hydroxide 30.39 mg.

Excipients (core): microcrystalline cellulose - 167.81 mg, croscarmellose sodium - 16.00 mg, povidone-K25 - 12.00 mg, magnesium stearate-3.80 mg.

Auxiliary substances (shell): hypromellose - 4.80 mg, macrogol-4000 - 1.20 mg, titanium dioxide - 2.00 mg.

Description:

Tablets coated with a film coat of white or almost white color. Allowed a slight marbling surface.

On the fracture of the tablets, the nucleus is almost white and the film membrane is visible.

Dosage of 75 mg + 15.2 mg - round, biconcave form;

dosage of 150 mg + 30.39 mg - round, biconcave, with a risk on one side.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

N.02.B.A.51 Acetylsalicylic acid in combination with other drugs, excluding psycholeptics

Pharmacodynamics:

At the core of the mechanism of action acetylsalicylic acid (ASA) is irreversible inhibition of cyclooxygenase (COX-1), which blocks the synthesis of thromboxane A₂ and aggregation of platelets is suppressed. It is believed that ASA has other mechanisms for suppressing platelet aggregation, which expands its use in various vascular diseases. ASA also has an anti-inflammatory, analgesic, antipyretic effect. The anti-inflammatory effect is associated with a decrease in blood flow due to inhibition of prostaglandin E synthesis2.

Magnesium hydroxide, which is part of the preparation Phasostabil, has an antacid effect and protects the mucous membrane of the gastrointestinal tract from the effects of ASA.

Pharmacokinetics:

Suction

After oral administration ASA is quickly and almost completely absorbed from the gastrointestinal tract.Simultaneous food intake slows down absorption. Partially metabolized during absorption.

Distribution and Metabolism

During and after absorption, ASA is converted to the main metabolite, salicylic acid, which is metabolized under the influence of enzymes, mainly in the liver, with the formation of metabolites (phenyl salicylate, glucuronide salicylate and salicyluric acid) found in many tissues and body fluids.

Among women the metabolism process is slower (less enzyme activity in the blood serum).

The maximum concentration of ASA in the blood plasma is reached in 10-20 minutes after ingestion, salicylic acid - after 0.3-2 hours. ASA and salicylic acid are highly associated with blood plasma proteins and are rapidly distributed in the body. The degree of binding of salicylic acid to blood plasma proteins depends on the concentration, not linear. At low concentrations (less than 100 μg / ml), up to 90% of salicylic acid binds to blood plasma proteins, at high concentrations (over 400 μg / ml) - up to 75%.

Bioavailability of ASA is 50-68%, salicylic acid - 80-100%. Salicylic acid penetrates the placental barrier, is found in breast milk.

With renal failure, during pregnancy and in newborns salicylates can displace bilirubin from bonding with albumin and promote the development of bilirubin encephalopathy.

Excretion

ASA and its metabolites are excreted mainly by the kidneys. The half-life of ASA is 15-20 minutes, salicylic acid 2-3 hours with low-dose ASA and significantly increased with ASA in high doses as a result of saturation of enzyme systems. Unlike other salicylates, with repeated administration of the drug, unhydrolyzed ASA does not accumulate in the blood serum. In patients with normal renal function, 80-100% of a single dose of ASA is excreted by the kidneys within 24-72 hours.

Magnesium hydroxide in the applied doses does not affect the bioavailability of ASA.

Indications:

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

- prevention of recurrent myocardial infarction and thrombosis of blood vessels;

- prevention of thromboembolism after surgical interventions on vessels (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty);

- unstable angina.

Contraindications:

- Hypersensitivity to ASA, drug auxiliaries and other non-steroidal anti-inflammatory drugs (NSAIDs);

- hemorrhage in the brain;

- propensity to bleed (insufficiency of vitamin K, thrombocytopenia, hemorrhagic diathesis);

- chronic heart failure of a functional class III-IV by classification NYHA;

- The bronchial asthma, induced by the intake of salicylates and NSAIDs;

- complete or partial combination of asthma, recurrent nasal polyposis, and paranasal sinuses, and intolerance to ASA and other NSAIDs, including cyclooxygenase-2 inhibitors (COX-2) (including history);

- erosive-ulcerative lesion of the gastrointestinal tract (in the phase of exacerbation);

- gastrointestinal bleeding;

- severe renal failure (creatinine clearance (CK) less than 30 ml / min.);

- hepatic insufficiency (class B and C according to Child-Pugh classification);

- pregnancy (I and III trimesters), the period of breastfeeding;

- deficiency of glucose-6-phosphate dehydrogenase;

- simultaneous reception with methotrexate (more than 15 mg per week);

- children's age till 18 years.

Carefully:

With gout, hyperuricemia, history of gastrointestinal ulcers or gastrointestinal bleeding, renal failure of mild and moderate severity (QC more than 30 ml / min), liver failure (class A according to Child-Pugh classification), bronchial asthma , hay fever, polyposis of the nose, allergic conditions, in the second trimester of pregnancy, with diabetes, elderly; with simultaneous use with the following drugs: methotrexate (less than 15 mg per week), anticoagulants, thrombolytic and antiplatelet agents, NSAIDs and salicylates in high doses, narcotic analgesics, sulfonamides (including co-trimoxazole), inhibitors of carbonic anhydrase (acetazolamide), digoxin, lithium, hypoglycemic agents for oral administration (sulfonylureas derivatives), insulin, valproic acid, selective serotonin reuptake inhibitors, ibuprofen, systemic glucocorticosteroids, ethanol (alcohol-containing preparations, beverages) (see section "Interaction with other medicines").

Pregnancy and lactation:

Inhibition of prostaglandin synthesis can have a negative effect on pregnancy and the development of an embryo or fetus.

The use of salicylates in doses of more than 300 mg per day in the first 3 months of pregnancy is associated with an increased incidence 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 only be used with a strict risk and benefit assessment, preferably at doses not exceeding 150 mg / day and for a short time.

In the last trimester of pregnancy, salicylates in high doses (more than 300 mg / day) cause inhibition 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 hemorrhage, especially in premature infants. The use of salicylates in the last trimester of pregnancy is contraindicated.

Available clinical data are not sufficient to determine whether or not the drug can be used during breastfeeding. Salicylates and their metabolites penetrate into breast milk in small amounts. The accidental intake of salicylates during lactation is not accompanied by the development of adverse reactions in the child and does not require the cessation of breastfeeding.

Before using acetylsalicylic acid during breastfeeding, the potential benefit of therapy with a drug relative to the potential risk to infants should be assessed.

However, with prolonged use of the drug or its use in a high dose, breast-feeding should be stopped immediately.

Dosing and Administration:

Inside, the film-coated tablets of the drug Fasostabil swallow whole, washed down with water.

The drug Fasostabil is designed for long-term treatment. The duration of treatment is determined by the doctor.

- Primary prevention of cardiovascular disease, such as thrombosis and acute heart failure in the presence of risk factors (for example, diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking, advanced age)

1 tablet of the preparation Phasostabil, containing ASA in a dose of 150 mg in the first day, then 1 tablet containing ASA in a dose of 75 mg once a day.

- Prevention of repeated myocardial infarction and thrombosis of blood vessels

1 tablet of the drug Phasostabil, containing ASA in a dose of 75-150 mg once a day.

- Prevention of thromboembolism after surgical interventions on vessels (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty)

1 tablet of the drug Phasostabil, containing ASA in a dose of 75-150 mg once a day.

- Unstable angina

1 tablet of the drug Phasostabil, containing ASA in a dose of 75-150 mg once a day.

When you skip the next dose of the drug Fasostabil must be taken missed dose of the drug as soon as the patient remembers it. To avoid doubling the dose, do not take the missed pill if the time of taking the next dose is approaching.

Features of the action for the first time you receive or cancel preparation were not observed.

Side effects:

The frequency of adverse reactions listed below, in accordance with the classification of the World Health Organization,was determined according to the following: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), including individual messages.

From the immune system: infrequently - urticaria, angioedema (Quincke's edema), skin rash, skin itch, rhinitis, edema of the nasal mucosa; rarely - Anaphylactic shock, cardio-respiratory distress syndrome.

From the gastrointestinal tract: Often - heartburn; often - nausea, vomiting; infrequently - pain in the abdomen, ulcers of the mucous membrane of the stomach and duodenum, including perforating (rare), gastrointestinal bleeding; rarely - stomatitis, esophagitis, erosive lesions of the upper sections of the gastrointestinal tract (including strictures), colitis, irritable bowel syndrome.

On the part of the respiratory system, the organs of the thorax and the mediastinum: often - bronchospasm.

From the side of the blood and lymphatic system: Often - increased bleeding; rarely - anemia; rarely - Aplastic anemia, hypoprothrombinemia, thrombocytopenia, neutropenia, leukopenia, eosinophilia, agranulocytosis.

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

From the nervous system: often - headache, insomnia; infrequently - dizziness, drowsiness; rarely - noise in the ears, intracerebral haemorrhage.

From the side of the kidneys and urinary tract: rarely - impaired renal function.

Impact on the results of laboratory and instrumental studies: rarely - Increased activity of "liver" enzymes.

Overdose:

The syndrome of salicylism develops when taking acetylsalicylic acid at 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 context of incorrect therapeutic use (chronic poisoning) or a single accidental or intentional intake of a toxic dose of the drug by an adult or child acute poisoning).

Overdose is especially dangerous in elderly patients.

Symptoms of overdose with mild and moderate severity (single dose less than 150 mg / kg):

Dizziness, noise in the ears, hearing loss, increased sweating, nausea and 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 with an average and severe severity (single dose of 150 mg / kg-300 mg / kg - an average severity, more than 300 mg / kg - severe degree of poisoning):

Respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, hyperventilation, non-cardiogenic pulmonary edema, respiratory depression, asphyxia; from the cardiovascular system: a violation of the rhythm of the heart, a marked decrease in blood pressure, suppression of cardiac activity; from the water-electrolyte balance: dehydration, disturbance of kidney function from oliguria up to the development of renal failure, characterized by hypokalemia, hypernatremia, hyponatremia; impaired 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 the central nervous system (drowsiness, confusion, coma, convulsions).

Treatment: immediate hospitalization in specialized departments for emergency therapy - gastric lavage, repeated intake of activated carbon, restoration of water-electrolyte balance and acid-base state, forced alkaline diuresis, symptomatic therapy.

Interaction:

With the simultaneous use of AC K increases the effect and increases the risk of toxicity:

- methotrexate (by reducing renal clearance and displacing it from the connection with blood plasma proteins);

- valproic acid (due to the displacement of plasma from the connection with proteins);

ASA enhances the action and increases the risk of unwanted reactions:

- narcotic analgesics, other non-steroidal anti-inflammatory drugs (due to the synergy of the action)

- hypoglycemic agents for oral administration (derivatives of sulfonylureas) and insulin due to hypoglycemic properties of ASA itself in high doses (more than 2 g per day) and displacement of sulfonylurea derivatives from the connection with blood plasma proteins

- thrombolytic agents, heparin, indirect anticoagulant (ticlopidine, warfarin), antiplatelet agents (including clopidogrel, dipyridamole) - due to the synergy of the main therapeutic effects and the displacement of plasma from the connection with proteins;

- sulfonamides, including co-trimoxazole - due to the displacement of plasma from the connection with proteins and increase in the concentration in the blood plasma;

- inhibitors of carbonic anhydrase (acetazolamide). Simultaneous use with ASA can lead to the development of severe acidosis and increase the toxic effect on the central nervous system;

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

- selective serotonin reuptake inhibitors (including sertraline, paroxetine), which can lead to an increased risk of bleeding from the upper gastrointestinal tract (synergy with ASA);

- the additive effect is observed with simultaneous reception of ASA from ethanol (alcohol): the damage to the mucous membrane of the gastrointestinal tract increases and the bleeding time is prolonged (due to the additive effect of ethanol and ASA).

Reduce the antiplatelet effect of ASA:

- ibuprofen (as a consequence of antagonism with respect to inhibition of platelet aggregation);

- systemic glucocorticosteroids (with the exception of hydrocortisone used for the replacement therapy of Addison's disease) (enhance the elimination of salicylates);

- antacids containing aluminum and / or magnesium hydroxide, colestyramine (reduce the absorption of ASA in the gastrointestinal tract);

ASA in low doses weakens the effect of uricosuric agents (benzbromarone, probenecid, sulfinpyrazone) due to competitive tubular elimination of uric acid.

ASC in high doses, like other NSAIDs, can reduce the antihypertensive effect diuretics (due to a decrease in the glomerular filtration rate due to suppression of the synthesis of renal prostaglandins) and antihypertensive means. In particular, due to the competitive blockade of prostacyclin synthesis, the effectiveness of angiotensin-converting enzyme (ACE) inhibitors may be reduced.

Special instructions:

The drug should be used as directed by a doctor.

ASA can provoke bronchospasm, as well as cause seizures of bronchial asthma and other reactions of hypersensitivity.Risk factors are the availability of a history of asthma, hay fever, nasal polyposis, chronic diseases of the respiratory system as well as of allergic reactions to other drugs (e.g., skin reactions, pruritus, urticaria).

ASA can cause bleeding of varying severity during and after surgical interventions.

A few days before the planned surgical intervention, the risk of developing bleeding should be assessed compared with the risk of developing ischemic complications in patients taking low-dose ASA. If the risk of developing bleeding is significant, ASA should be temporarily discontinued.

Simultaneous use of ASA with anticoagulants, thrombolytic agents and antiplatelet agents is accompanied by an increased risk of bleeding.

If the renal function is impaired (KC more than 30 ml / min), as well as in cases of circulatory disorders resulting from arteriosclerosis of the renal arteries, chronic heart failure, extensive surgical intervention, sepsis, cases of massive bleeding,because in all these cases, ASA may increase the risk of developing acute renal failure / impaired renal function (see "With caution").

It is known that the risk of developing acute renal failure increases with the joint use of other PPA with ACE inhibitors or diuretics.

In patients with mild to moderate hepatic impairment, liver function should be monitored regularly (see "With caution.")

ASA in low doses can provoke the development of gout in predisposed patients (having decreased uric acid excretion).

The combination of ASA with methotrexate is accompanied by an increased incidence of adverse effects on the part of the hematopoiesis, combined use with valproic acid increases the risk of its toxicity. During the first weeks of simultaneous use of the drug Fasostabil and methotrexate at a dose of less than 15 mg per week, a blood test should be performed weekly. Careful monitoring should be carried out in the presence of even small violations of kidney function, as well as in elderly patients (see "Contraindications", "FROM caution, "" Interaction with other drugs ").

Simultaneous use of ASA with anticoagulants, thrombolytic and antiaggregant drugs is associated with an increased risk of bleeding and damaging effects on the mucous membrane of the gastrointestinal tract (see sections "With caution", "Interaction with other drugs").

It is not recommended simultaneous use of the drug Phasostabil with ibuprofen in patients with an increased risk of developing cardiovascular diseases, since a decrease in the antiplatelet effect of ASA in doses up to 300 mg leads to a decrease in cardioprotective effects. Patients receiving ibuprofen to relieve pain, you should inform your doctor about this (see the sections "With caution", "Interaction with other medicines").

It is recommended to monitor the concentrations of digoxin and lithium in the blood plasma at the beginning or at the end of simultaneous application of the drug Phasostabil; a dose adjustment may be required (see sections "With caution", "Interaction with other drugs").

When combined with diuretics and antihypertensives (eg, ACE inhibitors), possible reduction in their effectiveness should be considered (see section "Interaction with other drugs").

High doses of ASA have a hypoglycemic effect, which must be borne in mind when prescribing it to patients with diabetes mellitus receiving hypoglycemic agents for ingestion and insulin.

With the simultaneous use of systemic glucocorticosteroids and salicylates, it should be remembered that during treatment, the concentration of salicylates in the blood is reduced, and after overtreatment of systemic glucocorticosteroids, salicylates can be overdosed.

With prolonged use of low doses of ASA as antiplatelet therapy, care should be taken in elderly patients because of the risk of developing gastrointestinal bleeding.

With prolonged use of the drug, Fasostabil should periodically monitor the general blood test and analysis of feces for latent blood, as well as the functional state of the liver.

With the simultaneous administration of ASA with alcohol, the risk of damage to the mucous membrane of the gastrointestinal tract and prolongation of bleeding time are increased.

In severe forms of deficiency of glucose-6-phosphate dehydrogenase, ASA can cause hemolysis and hemolytic anemia (see the section "Contraindications"). Factors that increase the risk of hemolysis and hemolytic anemia are fever, acute infections and high doses of ASA.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment with the drug Fasostabil, care must be taken when driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 75 mg + 15.2 mg and 150 mg + 30.39 mg.

Packaging:

For 10, 20, 25 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets in cans of polyethylene terephthalate for medicinal products sealed with caps screwed on with a first opening control or a "push-turn" system of polypropylene or polyethylene or cans polypropylene for drugs, sealed with lids pulled with the control of the first opening of polyethylene,or cans of polypropylene for medicines sealed with caps tightened with the control of the first opening of high-pressure polyethylene, glass bottles of dark glass sealed with a screw cap of polyethylene with a built-in removable silica gel capsule and with a control ring of the first opening.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:LP-003790

Date of registration:17.08.2016

Expiration Date:17.08.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp09.10.2016

Illustrated instructions

Instructions

Fazostabil (Fazostabil)