Fastokar^® (Tablets) Instructions for Use

Marketing Authorization Holder

Artelar, LLC (Russia)

Manufactured By

Avva Rus, JSC (Russia)

ATC Code

B01AC30 (Platelet aggregation inhibitors in combination)

Active Substances

Magnesium hydroxide (Ph.Eur.)

Acetylsalicylic acid (Ph.Eur.)

Dosage Forms

	Fastokar®	Film-coated tablets, 75 mg+15.2 mg: 30 or 100 pcs.
		Film-coated tablets, 150 mg+30.39 mg: 30 or 100 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the core on the cross-section is white or almost white.

* (calculated as 100% substance).

Excipients: corn starch – 9.5 mg, potato starch – 2 mg, magnesium stearate – 1.15 mg, crospovidone XL-10 – 0.58 mg, microcrystalline cellulose 102 – to obtain an uncoated tablet with a mass of 115 mg.

Shell composition mixture for the preparation of film coating “Opadry^® 20A180003 white” [hypromellose 2910 – 30%, hyprolose – 30%, talc – 20%, titanium dioxide – 20%] – 118 mg.

30 pcs. – polymer jars (1) – cardboard packs.
100 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – dark glass bottles (1) – cardboard packs.
100 pcs. – dark glass bottles (1) – cardboard packs.

Film-coated tablets white or almost white, round, biconvex; the core on the cross-section is white or almost white.

* (calculated as 100% substance).

Excipients: corn starch – 19 mg, potato starch – 4 mg, magnesium stearate – 2.3 mg, crospovidone XL-10 – 1.15 mg, microcrystalline cellulose 102 – to obtain an uncoated tablet with a mass of 230 mg.

Shell composition mixture for the preparation of film coating “Opadry^® 20A180003 white” [hypromellose 2910 – 30%, hyprolose – 30%, talc – 20%, titanium dioxide – 20%] – 236 mg.

30 pcs. – polymer jars (1) – cardboard packs.
100 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – dark glass bottles (1) – cardboard packs.
100 pcs. – dark glass bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antiplatelet agent

Pharmacotherapeutic Group

Antiaggregant agent

Pharmacological Action

NSAID, antiplatelet agent.

The mechanism of action of acetylsalicylic acid is based on the irreversible inhibition of the COX-1 enzyme, resulting in the blockade of thromboxane A₂ synthesis and suppression of platelet aggregation. It is believed that Acetylsalicylic acid has other mechanisms of suppressing platelet aggregation, which expands its scope of 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 oral administration of the drug, 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 gastrointestinal mucosa and in the liver with the formation of salicylic acid under the action of enzymes. The bioavailability of salicylic acid is 80-100%.

C_max of acetylsalicylic acid in blood plasma is reached in 10-20 minutes after oral administration, of salicylic acid – in 0.3-2 hours. Acetylsalicylic acid and salicylic acid are highly bound to plasma proteins and are rapidly distributed in the body. The degree of binding of salicylic acid to plasma proteins depends on the concentration and is non-linear. At low concentrations (<100 mcg/ml) up to 90% of salicylic acid is bound to plasma proteins, at high concentrations (>400 mcg/ml) – up to 75%. Salicylic acid crosses the placental barrier and is found in breast milk.

Salicylic acid is metabolized under the influence of enzymes, mainly in the liver, with the formation of metabolites (phenyl salicylate, salicyl 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).

Acetylsalicylic acid and its metabolites are excreted mainly by the kidneys. T_1/2 of acetylsalicylic acid from blood plasma is 15-20 minutes, of salicylic acid – 2-3 hours when taking acetylsalicylic acid in low doses and increases significantly when taking acetylsalicylic acid in high doses due to 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 its binding with albumin and contribute to the development of bilirubin encephalopathy.

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

Indications

Primary prevention of cardiovascular diseases, such as thrombosis and acute heart failure in the presence of risk factors (e.g., diabetes mellitus, hyperlipidemia, arterial hypertension, obesity, smoking, old age); prevention of recurrent myocardial infarction and thrombosis of blood vessels; prevention of thromboembolism after vascular surgery (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty); unstable angina.

ICD codes

Dosage Regimen

Take orally, 1-2 hours after meals, with a full glass of water. Swallow the tablet whole; do not crush or chew.

Administer one single dose once daily. The standard dose for long-term antiplatelet prophylaxis is one 75 mg/15.2 mg tablet. For specific conditions, such as acute coronary syndrome, a higher dose of one 150 mg/30.39 mg tablet may be used initially, as directed by a physician.

This combination is intended for long-term, continuous use. Do not discontinue therapy without consulting your doctor, as this may increase the risk of cardiovascular events. The total duration of treatment is determined by the physician based on individual risk assessment.

No specific features of the drug’s action upon first administration or upon its withdrawal have been observed. Adhere strictly to the prescribed dosage schedule to maintain consistent antiplatelet effect.

Adverse Reactions

In general, preparations containing this combination are well tolerated.

From the nervous system frequent – headache, insomnia; infrequent – dizziness, drowsiness; rare – tinnitus, intracerebral hemorrhage.

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

From the respiratory system frequent – bronchospasm.

From the digestive system very frequent – heartburn; frequent – nausea, vomiting; infrequent – abdominal pain, ulcers of the gastric and duodenal mucosa, gastrointestinal bleeding; rare – perforation of gastric or duodenal ulcer, increased activity of liver enzymes; very rare – stomatitis, esophagitis, erosive lesions of the upper gastrointestinal tract (including with strictures), colitis, irritable bowel syndrome.

Allergic reactions infrequent – urticaria, angioedema, skin rash, skin itching, rhinitis, swelling of the nasal mucosa; very rare – anaphylactic shock, cardiorespiratory distress syndrome.

Other very rare – impaired renal function.

Contraindications

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; cerebral hemorrhage; tendency to bleeding (thrombocytopenia, hemorrhagic diathesis, vitamin K deficiency); severe renal failure (creatinine clearance less than 30 ml/min); severe hepatic failure (more than 9 points on the Child-Pugh scale); I and III trimesters of pregnancy; lactation period; glucose-6-phosphate dehydrogenase deficiency; simultaneous use with methotrexate (in a dose of ≥15 mg per week); age under 18 years (efficacy and safety not established).

With caution

Gout, hyperuricemia; history of ulcerative gastrointestinal tract lesion or gastrointestinal bleeding; mild and moderate renal failure (creatinine clearance more than 30 ml/min) and/or hepatic 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; period before surgery; simultaneous use with certain drugs (including methotrexate in a dose of <15 mg per week, valproic acid, anticoagulants, thrombolytic and antiplatelet agents, NSAIDs and derivatives of acetylsalicylic acid in high doses, narcotic analgesics, sulfonamides /including co-trimoxazole/, carbonic anhydrase inhibitors /acetazolamide/, digoxin, lithium, oral hypoglycemic agents /sulfonylurea derivatives/, insulin, selective serotonin reuptake inhibitors, ibuprofen, systemic corticosteroids); concomitant use with ethanol (ethanol-containing drugs, alcoholic beverages); II trimester of pregnancy.

Use in Pregnancy and Lactation

The use of salicylates in high doses in the first trimester of pregnancy is associated with an increased frequency of fetal developmental defects (cleft palate, heart defects). Use in the first trimester of pregnancy is contraindicated. In the second trimester of pregnancy, it can be prescribed only taking into account a strict assessment of the benefit of treatment for 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 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 use immediately before childbirth can cause intracranial hemorrhage, especially in premature infants. Use in the third trimester of pregnancy is contraindicated.

Salicylates and their metabolites penetrate into breast milk in small amounts. Clinical data to assess the safety of acetylsalicylic acid use during breastfeeding are insufficient. Before prescribing acetylsalicylic acid during lactation, the expected benefit of therapy for the mother and the potential risk for breastfed 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 discontinuation of breastfeeding. However, if long-term use of this combination is necessary, breastfeeding should be stopped immediately.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment (more than 9 points on the Child-Pugh scale).

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

Use in Renal Impairment

Contraindicated in severe renal impairment (creatinine clearance less than 30 ml/min).

The drug should be prescribed with caution in mild and moderate renal impairment (creatinine clearance more than 30 ml/min).

Pediatric Use

Contraindicated in children under 18 years of age (efficacy and safety not established).

Geriatric Use

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

Special Precautions

Acetylsalicylic acid can provoke bronchospasm, as well as cause attacks of bronchial asthma and other hypersensitivity reactions. Risk factors are a history of bronchial asthma, hay fever, polyposis of the nose and paranasal sinuses, chronic respiratory diseases, as well as allergic reactions (e.g., 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. Several days before planned surgery, the risk of bleeding should be assessed against the risk of ischemic complications in patients taking low-dose acetylsalicylic acid. If there is a significant risk of bleeding, the drug should be temporarily discontinued.

In case of impaired renal function (creatinine clearance more than 30 ml/min), as well as in case of circulatory disorders arising from atherosclerosis of the renal arteries, chronic heart failure, extensive surgery, sepsis, cases of massive bleeding, caution should be exercised, since in all the listed cases ASA can increase the risk of acute renal failure/deterioration of renal function. It is known that the risk of 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 and moderate hepatic impairment, liver function should be regularly monitored.

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

When acetylsalicylic acid is used concomitantly with anticoagulants, thrombolytic and antiplatelet drugs, the risk of bleeding and damaging effects on the gastrointestinal mucosa increases, so bleeding time should be monitored.

Concomitant 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 about this.

Monitoring of plasma concentrations of digoxin and lithium is recommended at the beginning or at the end of concomitant use with the combination Acetylsalicylic acid+Magnesium hydroxide; dose adjustment may be required.

With the concomitant use of systemic corticosteroids and acetylsalicylic acid, the concentration of salicylates in the blood plasma decreases, and after the withdrawal of systemic corticosteroids, an overdose of salicylates is possible. In addition, with concomitant use, the risk of damage to the gastrointestinal mucosa and bleeding increases.

The use of acetylsalicylic acid in doses exceeding the recommended therapeutic doses (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 long-term use, a complete blood count and fecal occult blood test, as well as liver functional state, should be periodically monitored.

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

Acetylsalicylic acid in high doses has a hypoglycemic effect, which should be taken into account 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.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, caution should be exercised when driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

When used concomitantly, Acetylsalicylic acid enhances the effect and increases the risk of toxicity of the following drugs

• methotrexate (due to reduced renal clearance and displacement from plasma protein binding);
• valproic acid (due to displacement from plasma protein binding).

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

• narcotic analgesics, other NSAIDs (due to synergy of action);
• oral hypoglycemic agents (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 plasma protein binding);
• thrombolytic agents, heparin, indirect anticoagulants (including ticlopidine, warfarin), antiplatelet agents (including clopidogrel, dipyridamole) due to the synergy of the main therapeutic effects and displacement from plasma protein binding;
• sulfonamides (including co-trimoxazole) due to displacement from plasma protein binding and an increase in plasma concentration;
• carbonic anhydrase inhibitors (acetazolamide). Concomitant use with acetylsalicylic acid may lead to the development of severe acidosis and increased toxic effects on the CNS;
• digoxin and lithium – due to a decrease in the renal excretion of digoxin and lithium with an increase in their plasma concentration;
• selective serotonin reuptake inhibitors (including sertraline, paroxetine) – due to a synergistic effect (with an increased risk of upper gastrointestinal bleeding).
• ethanol (alcohol and ethanol-containing preparations) – 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 regarding the suppression of platelet aggregation);
• systemic corticosteroids (increase 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 inhibition of renal tubular excretion of uric acid.

Acetylsalicylic acid in high doses, like other NSAIDs, may reduce the antihypertensive effect of diuretics (due to a decrease in the glomerular filtration rate resulting from the inhibition of renal prostaglandin synthesis) and antihypertensive agents. In particular, due to competitive blockade of prostacyclin synthesis, the effectiveness of ACE inhibitors may be reduced.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.