Effient 10 mg, 28 film-coated tablets

Release form, composition and packaging

Film-coated tablets

beige, oblong, with “4759” engraved on one side and “10 MG” on the other.

Excipients: mannitol - 67.21 mg, hypromellose - 5.285 mg, croscarmellose sodium - 11 mg, microcrystalline cellulose - 78.75 mg, magnesium stearate - 1.58 mg.

Shell composition:

opadry II beige (lactose monohydrate - 2.1 mg, hypromellose - 3.85 mg, titanium dioxide - 1.58 mg, triacetin - 0.7 mg, yellow iron oxide dye - 0.46 mg, red iron oxide dye - 0.06 mg) - 8.75 mg, talc - up to 0.001 mg.

pharmachologic effect

Mechanism of action

The antiplatelet drug prasugrel is an antagonist of the P2Y12 adenosine diphosphate (ADP) receptor and inhibits platelet activation and aggregation. Since platelets are involved in the development of atherosclerotic complications, inhibition of their function helps reduce the incidence of cardiovascular complications (such as death from a cardiovascular cause, myocardial infarction or stroke).

In 89% of healthy volunteers and patients with atherosclerotic artery disease, at least 50% inhibition of platelet aggregation was achieved 1 hour after taking a 60 mg loading dose of prasugrel. After 3-5 days of taking prasugrel at a maintenance dose of 10 mg/day (after previous administration of a loading dose of the drug), i.e. at average steady state, platelet aggregation inhibition is about 70%.

Platelet aggregation after cessation of prasugrel therapy gradually returns to baseline values: within 7-9 days after a single loading dose of prasugrel 60 mg and within 5 days after stopping the maintenance dose at steady state.

Data on switching from one drug to another

When switching to prasugrel after treatment with clopidogrel at a daily dose of 75 mg for 10 days, similar or higher inhibition of platelet aggregation is observed. In a study of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), switching from an initial loading dose of 600 mg of clopidogrel or placebo taken before coronary angiography to a 60 mg loading dose of prasugrel taken at the time of PCI resulted in similar increase in inhibition of platelet aggregation within 72 hours.

Efficiency and safety

A clinical trial in patients with ACS at risk for unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) and patients with ST-segment elevation myocardial infarction (NSTEMI) undergoing PCI compared prasugrel and clopidogrel taken with acetylsalicylic acid (ASA) and other drugs, according to treatment standards.

Patients receiving prasugrel (60 mg loading dose, followed by 10 mg daily dose) or clopidogrel (300 mg loading dose, followed by 75 mg daily dose) were treated for an average of 14.5 months with a minimum of 6 months of follow-up. Patients received ASA (from 75 to 325 mg 1 time/day). The criterion for effectiveness is the time to the first incident of non-fatal heart attack, non-fatal stroke or death from a cardiovascular cause.

Analysis of the combined endpoint in the entire population of patients with ACS (combined population with UA/NSTEMI and STMI) was based on demonstrating the statistical superiority of prasugrel compared to clopidogrel in the group of patients with UA/NSTEMI (p ® shows higher efficacy compared with clopidogrel in reducing the incidence of the primary composite endpoint as well as the incidence of secondary endpoints, including stent thrombosis. The advantage of prasugrel is observed during the first 3 days and is maintained until the end of the study. The superior effectiveness is accompanied by an increase in the incidence of major bleeding ( see sections "Precautions" and "Side Effects"). The effectiveness of prasugrel does not depend on age, gender, body weight, geographic region, concomitant therapy, including heparin, bivalirudin, IV GPIIb/IIIa inhibitors, lipid-lowering drugs, beta- adrenergic blockers and ACE inhibitors, ASA dosages (from 75 to 325 mg 1 time/day).

The benefits are manifested mainly in a significant reduction in the incidence of non-fatal myocardial infarction. In patients with diabetes, there was also a significant reduction in the incidence of the primary and all secondary composite endpoints (non-fatal myocardial infarction, non-fatal stroke or death from a cardiovascular cause). The observed benefits of prasugrel are less pronounced in patients 75 years of age and older than in patients younger than 75 years of age (see Pharmacokinetics, Dosage Regimen, Precautions, and Adverse Reactions). For patients with diabetes, STEMI, increased risk of stent thrombosis, or recurrent disease in the group of patients 75 years and older, the benefit of prasugrel is more pronounced. In the entire ACS population, analysis for each secondary endpoint showed a significant advantage of prasugrel compared with clopidogrel in the incidence of events such as detected or possible stent thrombosis at the end of the study, death from a cardiovascular cause, non-fatal myocardial infarction, non-fatal stroke, emergency target vessel revascularization within 30 days or readmission due to coronary ischemic events before the end of the study.

Analysis of the incidence of death from all causes showed no significant difference between prasugrel and clopidogrel in the population of all patients with ACS. Prasugrel was associated with a 50% reduction in stent thrombosis during the 15-month follow-up period for both bare-metal and drug-eluting stents.

Despite the increased incidence of bleeding with prasugrel therapy, analysis of the composite endpoint of death from any cause, nonfatal myocardial infarction, nonfatal stroke, and non-CABG-related TIMI “major” bleeding shows an advantage for Effient® in comparison with clopidogrel.

Pharmacokinetics Effient

Prasugrel is a prodrug and is rapidly metabolized in vivo to active and inactive metabolites. The AUC value is characterized by moderate to low variability within the population (27%) and within an individual patient (19%). The pharmacokinetic parameters of prasugrel are similar in healthy volunteers, patients with stable atherosclerotic disease and patients who have undergone percutaneous coronary intervention.

Suction

When taken orally, prasugrel is rapidly absorbed and metabolized. The time to reach the maximum concentration (Tmax) of the active metabolite in the blood serum is reached approximately 0.5 hours after administration. The AUC of the active metabolite increases in direct proportion to the therapeutic dose of the drug.

In healthy volunteers, high-fat and high-calorie foods do not affect the AUC of the active metabolite, but Cmax decreases by 49%, and Tmax increases from 0.5 hours to 1.5 hours. Taking a loading dose of the drug Effient® on an empty stomach may provide a faster onset of action (see section " Dosage regimen").

Distribution

The binding of the active metabolite of prasugrel to human serum albumin is 98%.

Metabolism

Prasugrel is not detectable in plasma after oral administration. Prasugrel is rapidly hydrolyzed in the intestine to thiolactone, which is then converted to its active metabolite mainly by cytochrome P450 isoenzymes such as CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. The active metabolite is converted to two inactive metabolites by S-methylation or conjugation with cysteine.

In healthy volunteers, patients with a stable course of atherosclerotic process and patients who underwent PCI taking Effient®, there was no effect of genetic variations in the isoenzymes CYP2B6, CYP2C9, CYP2C19 or CYP3A5 on the pharmacokinetic parameters of prasugrel or the suppression of platelet aggregation.

Removal

Approximately 68% of prasugrel is excreted in the urine and about 27% in the feces in the form of inactive metabolites. T1/2 of the active metabolite is about 7.4 hours (interval from 2 to 15 hours).

Special patient groups

Elderly patients

. The study shows that in healthy volunteers aged 20 to 80 years, the pharmacokinetics of prasugrel or inhibition of platelet aggregation does not depend on the age of the patients. The AUC of the active metabolite is 19% higher in very elderly patients (75 years and older) compared to patients younger than 75 years. Prasugrel should be used with caution in patients 75 years of age and older due to the potential risk of bleeding in this population (see Dosage Regimen and Precautions). In a study of patients with stable atherosclerotic disease, the AUC of the active metabolite in a population of patients 75 years of age and older receiving 5 mg of prasugrel was approximately half that of patients younger than 65 years of age receiving 10 mg of prasugrel, and only in patients taking 5 mg, the antiplatelet effect of prasugrel is reduced.

Body mass

. The AUC of the active metabolite prasugrel is approximately 30-40% greater in healthy volunteers and patients weighing less than 60 kg compared to those weighing 60 kg or more.

Floor

. In healthy volunteers and patients, the pharmacokinetic parameters of prasugrel do not differ between men and women.

Ethnicity

. In clinical pharmacological studies, the AUC of the active metabolite (weight-adjusted) was approximately 19% higher in Chinese, Japanese and Korean subjects compared to Caucasians. There were no differences between individuals of Chinese, Japanese, and Korean ethnicity. In blacks and Hispanics, exposure is comparable to that in Caucasians. No dose adjustment is required based on ethnicity.

Kidney failure

. For patients with renal impairment, including patients with end-stage renal failure (ESRD), no dose adjustment is required. The pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation are similar in patients with moderate renal impairment (GFR 30-49 ml/min/1.73 m2 body surface area) and in healthy volunteers. The inhibition of platelet aggregation caused by prasugrel was also comparable in patients with ESRD requiring hemodialysis and healthy volunteers, although in patients with ESRD the Cmax and AUC of the active metabolite were reduced by 51% and 42%, respectively.

Liver failure

. For patients with mild to moderate hepatic impairment (class A and B on the Child-Pugh scale), no dose adjustment is required. The pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation in patients with mild to moderate hepatic impairment and healthy volunteers are comparable. The pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic impairment (Child-Pugh class C) have not been studied. Prasugrel is contraindicated in such patients (see section “Contraindications”).

Children and adolescents under 18 years of age

. The pharmacokinetics and pharmacodynamics of prasugrel have not been studied in children and adolescents.

Effient instructions for use

INSTRUCTIONS for using Effient

Composition Active ingredient: 1 tablet contains 5 mg or 10 mg prasugrel (in the form of hydrochloride) Excipients: Tablet core: microcrystalline cellulose, mannitol (E 421), croscarmellose sodium, hypromellose (E 464), magnesium stearate Tablet shell: lactose, hypromellose (E 464), titanium dioxide (E 171), triacetin (E 1518), red iron oxide (E 172) (for 10 mg tablets), yellow iron oxide (E 172), talc.

Dosage form Film-coated tablets.

Pharmacological group Antithrombotic agents. Antiplatelet agents. ATS code B01A C22.

Indications Effient in combination with acetylsalicylic acid is indicated for the prevention/reduction of atherothrombotic events in patients with acute coronary syndrome (ACS) (eg, unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) when percutaneous coronary intervention (PCI) is performed).

Contraindications Hypersensitivity to the active substance or to any auxiliary component. Active pathological bleeding. History of stroke or transient ischemic attack. Severe liver failure (class C on the Child-Pugh scale).

Method of administration and dosage: Use orally, regardless of food intake. DO NOT crush or break the tablet. Adults. The use of Effient is started with a loading single dose of 60 mg, and then treatment is continued with 10 mg once a day. Patients taking Effient should take acetylsalicylic acid (75 mg to 325 mg) per day. In patients with ACS (acute coronary syndrome) undergoing percutaneous coronary intervention (PCI), premature discontinuation of any antiplatelet drug, including Effient, may result in an increased risk of thrombosis, myocardial infarction, or death depending on the underlying disease. It is recommended to continue treatment for 12 months unless discontinuation of Effient is clinically indicated. Elderly patients (≥75 years). The use of Effient in patients ≥75 years of age is not recommended. If, after a careful individual benefit/risk assessment, the physician decides that treatment is necessary in patients ≥75 years of age, a single 60 mg loading dose of prasugrel should be prescribed and then a 5 mg dose may be considered. Patients weighing <60 kg. Effient should be used in a single loading dose of 60 mg, and then continue to administer a dose of 5 mg once a day. Kidney failure. No dosage adjustment is required for persons with impaired renal function, including persons with end-stage renal disease. Experience in treating patients with renal failure is limited. Liver failure. No dosage adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh classes A and B); treatment experience is limited.

Adverse reactions bleeding Bleeding not associated with coronary artery bypass grafting (CABG) Table 1 Prevalence of bleeding a not associated with CABG (% of patients) Adverse reactions Prasugrel b (N = 6741) Major bleeding according to Thieme classification c 2.2 Life-threatening d 1. 3 lethal 0.3 Severe clinical ICH e 0.3 Require inotropic agents 0.3 Require surgical intervention 0.3 Require blood transfusion (≥4 units) 0.7 Minor bleeding f 2.4 a Cases identified according to classification criteria are recorded TIMI. b Other standard therapy options were used appropriately. c Any intracranial hemorrhage or any clinically present bleeding associated with a decrease in hemoglobin level >5 g/dl. d Life-threatening is a subgroup of major bleeding according to TIMI, which also includes the types of bleeding highlighted below. Patients can be counted in more than one group. e ICH = intracranial hemorrhage. f Clinically significant bleeding associated with a decrease in hemoglobin >3 g/L to <5 g/dL. Bleeding associated with CABG During clinical trials, 437 patients underwent CABG. In these patients, the incidence of major and minor TIMI bleeding associated with CABG was 14.1% in the prasugrel group. The highest risk of bleeding in patients receiving prasugrel persisted until 7 days after the last dose of the drug. Table 2 summarizes hemorrhagic and non-hemorrhagic adverse reactions. Table 2 Common hemorrhagic and non-hemorrhagic adverse reactions Organs and systems very common (≥1/10) Rare (≥1/1000 to ≤1/100) Rare (≥1/10000 to ≤1/1000) frequency unknown From the circulatory system and lymphatic system anemia Thrombocytopenia thrombotic thrombocytopenic purpura (TTP) From the immune system Hypersensitivity, including angioedema From the organ of vision Hemorrhage in the eye From the vascular system hematoma From the respiratory system, chest and mediastinum Epistaxis hemoptysis From the gastrointestinal tract Gastrointestinal bleeding retroperitoneal bleeding rectal bleeding Bloody stool bleeding gums From the skin and subcutaneous tissue rashes ecchymosis From the kidneys and urinary system hematuria General disorders and condition of the injection area Hematoma at the injection site Bleeding at the injection site Trauma, poisoning and procedural complications contusion Bleeding after the procedure subcutaneous hematoma

Overdose Symptoms. An overdose of Effient may result in increased bleeding time and further bleeding complications. Treatment. There is no data on the reverse development of the pharmacological effect of prasugrel; however, if rapid correction of prolonged bleeding time is needed, transfusion of platelets and/or other blood products may be considered.

Use during pregnancy or breastfeeding No clinical studies have been conducted in pregnant or breastfeeding women. Effient should be used during pregnancy only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. It is unknown whether prasugrel is excreted into breast milk. The use of prasugrel during breastfeeding is not recommended.

Children It is not recommended to use prasugrel in children due to insufficient data on safety and effectiveness.

Features of use Risk of bleeding. Treatment with Effient in patients with an increased risk of bleeding should be carried out if the benefits of preventing ischemic complications outweigh the risk of serious bleeding. This is especially true for the following groups of patients: aged ≥75 years (see below); with a tendency to bleed (eg, due to recent trauma or surgery, recent or repeated gastrointestinal bleeding, active peptic ulcer disease); with body weight <60 kg. In this group of patients, a maintenance dose of 10 mg is not recommended. A maintenance dose of 5 mg should be used with concomitant medications that may increase the risk of bleeding, including oral anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), and fibrinolytics. To reverse the pharmacological effect of Effient in patients with active bleeding, platelet transfusions may be prescribed. The use of Effient in patients ≥75 years of age is not recommended and should be done after a careful individual benefit/risk assessment by a physician that demonstrates that the benefit in preventing ischemic complications outweighs the risk of serious bleeding. These patients had a higher risk of bleeding, including fatal bleeding, compared with patients <75 years of age. There is insufficient experience with prasugrel in patients with renal impairment and in patients with moderate hepatic impairment. These patients may have an increased risk of bleeding. Therefore, prasugrel should be used with caution in these patients. Patients should be informed that control of bleeding may take longer than usual if the patient is taking prasugrel (in combination with acetylsalicylic acid), and they should report any bleeding (location or duration of bleeding) to the doctor. Surgery. Patients should be advised to inform physicians, including dentists, that they are taking prasugrel before any planned surgery and before using any new drug. If a patient is scheduled for surgery and antiplatelet effects are not desired, Effient should be discontinued at least 7 days before surgery. An increase in the frequency (3-fold) and severity of bleeding may occur in patients undergoing CABG within 7 days before discontinuation of prasugrel. The benefits and risks of prasugrel should be carefully assessed in patients in whom coronary anatomy is uncertain and urgent CABG is necessary. Hypersensitivity reactions, including angioedema. Hypersensitivity reactions, including angioedema, have been observed in patients treated with prasugrel, including patients with a history of hypersensitivity reactions to clopidogrel. It is recommended to monitor for signs of hypersensitivity in patients with a known allergy to thienopyridines. Thrombocytopenic purpura (TPP). TPP has been reported with prasugrel. TPP is a dangerous condition that requires urgent treatment. Lactose. Patients with rare congenital problems of galactose intolerance, Sami lactose deficiency or glucose-galactose malabsorption should not use Effient.

The ability to influence the speed of reaction when driving vehicles or other mechanisms. No studies have been conducted on the ability to drive a car or operate machines. Prasugrel is expected to have no or negligible effect on the ability to drive a car or use machinery.

Interaction with other drugs and other types of interactions Warfarin. The use of coumarin derivatives other than warfarin has not been studied concomitantly with Effient. Due to the potential to increase the risk of bleeding, warfarin (or other coumarin derivatives) and Effient should be used after a risk/benefit assessment of the combination. NSAIDs. The concomitant use of prasugrel with NSAIDs has not been studied. Due to the ability to increase the risk of bleeding, the use of Effientu against the background of long-term use of NSAIDs is carried out taking into account the risk / benefit. Effient can be used together with drugs that are metabolized by cytochrome P 450 isoenzymes (including statins), or with drugs that are inducers or inhibitors of cytochrome P 450 enzymes. Effient can also be used together with acetylsalicylic acid, heparin, digoxin and drugs that increase gastric pH, including proton pump inhibitors and H2 blockers. In clinical studies, Effient was used with low molecular weight heparin, bivalirudin and glycoprotein IIb/IIIa inhibitors, and there was no evidence of clinically significant adverse drug interactions. The effect of other drugs on Effient Acetylsalicylic acid (ASA). Effient should be used together with ASA. Although the pharmacodynamic interaction with ASA results in an increased risk of bleeding, the efficacy and safety of prasugrel have been observed in patients taking concomitant ASA. Heparin. A single intravenous bolus dose of unfractionated heparin (100 units/kg) does not significantly affect Effient's inhibition of platelet aggregation. Effient also did not significantly change the effect of heparin on coagulation parameters. Thus, both drugs can be used together. There may be an increased risk of bleeding when Effient is used with heparin. Statins. Atorvastatin (80 mg per day) did not change the pharmacokinetics of Effient and its inhibition of platelet aggregation. Therefore, statins, which are substrates for CYP3A, are expected to affect the pharmacokinetics of Effient or its inhibition of platelet aggregation. Medicines that increase gastric pH. Daily co-administration with ranitidine (H2 blocker) or lansoprazole (proton pump inhibitor) did not change the AUC and T max of the active metabolites of prasugrel, but decreased C max by 14% and 29%, respectively, therefore the use of a 60 mg loading dose without concomitant administration of proton pump inhibitors pump may result in faster onset of action. CYP3A inhibitors. Ketoconazole (400 mg daily), a selective and potent inhibitor of cytochrome CYP3A4 and CYP3A5, did not affect Effient's suppression of platelet aggregation or the AUC and Tmax of the active metabolite prasugrel, but reduced Cmax from 34% to 46%. Therefore, CYP3A inhibitors such as azole antifungals, HIV protease inhibitors, clarithromycin, telithromycin, verapamil, diltiazem, indinavir, ciprofloxacin, and grapefruit juice are expected to affect the pharmacokinetics of the active metabolite. Inducers of cytochrome P 450. Rifampicin (600 mg daily), a strong inducer of CYP3A and CYP2B6, and an inducer of CYP2C9, CYP2C19 and CYP2C8, did not alter the pharmacokinetics of prasugrel. In summary, known CYP3A inducers such as rifampicin, carbamazepine and other cytochrome P450 inducers are not expected to significantly affect the pharmacokinetics of the active metabolite. Effect of Effient on other drugs Digoxin. Prasugrel had no significant effect on the pharmacokinetics of digoxin. Medicines that are metabolized by CYP2C9. Prasugrel did not inhibit CYP2C9 as it did not affect the pharmacokinetics of S-warfarin. Due to the potential for an increased risk of bleeding, warfarin and Effient should be used together with caution. Medicines that are metabolized by CYP2B6. Effient is a weak inhibitor of CYP2B6. In healthy volunteers, Effient reduced the effect of hydroxybupropion, a CYP2B6-mediated metabolite of bupropion, by 23%. Effient is not expected to affect the pharmacokinetics of drugs that are metabolized primarily by CYP2B6 (eg, cyclophosphamide, efavirenz).

Pharmacological properties Pharmacological. Prasugrel is an inhibitor of platelet activation and aggregation, acting through the irreversible binding of its active metabolite to P2Y12 adenosine diphosphate (ADP) receptors on platelets. Because platelets are involved in the initiation and/or development of platelet complications of atherosclerotic disease, inhibition of platelet function may result in a decreased incidence of cardiovascular events such as death, myocardial infarction, or stroke. At 1 hour after administration of a 60 mg loading dose of prasugrel, approximately 90% of patients had less than 50% inhibition of platelet aggregation function. The maximum suppression of platelet aggregation was about 80%. On average, after 3 to 5 days of taking 10 mg of prasugrel per day after taking a 60 mg loading dose, the inhibition of platelet aggregation was about 70%. Platelet aggregation gradually recovers after treatment to baseline values ​​within 7 to 9 days when using a loading dose of 60 mg prasugrel and 5 days after discontinuation of the maintenance dose.

Pharmacokinetics of Absorption Absorption and metabolism of prasugrel occur rapidly, reaching peak plasma concentrations (Cmax) in approximately 30 minutes. The release of the active metabolite (AUC) increases proportionally to the dose within the therapeutic dose range. The AUC of the active metabolite was unchanged due to the effect of fats and high-calorie foods, but Cmax was reduced by 49% and Cmax (Tmax) increased from 0.5 to 1.5 hours. In clinical studies, Effient was administered without food. Therefore, Effient can be used regardless of meals; however, administration of a loading dose of prasugrel on an empty stomach may result in a rapid onset of effect. Distribution: The binding of the active metabolite to human albumin is 98%. Metabolism Prasugrel is not detectable in blood plasma after oral administration. In the intestine, it undergoes rapid hydrolysis to thiolactone, which is then converted to its active metabolite in a single step of cytochrome P450 metabolism, mainly by CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. This active metabolite is further metabolized to two inactive compounds by S-methylation or conjugation with cysteine. Conclusion: Approximately 68% of a prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites. The half-life of the active metabolite is about 7.4 hours (range: 2 to 15 hours).

Basic physical and chemical properties of 5 mg yellow oval tablets. On one side of the tablet there is an identification mark, on the other - “5 MG”. 10 mg beige oval tablets. On one side of the tablet there is an identification mark, on the other - “10 MG”.

Shelf life: 2 years.

Storage conditions Store at a temperature not exceeding 30 0 C in the original packaging, out of the reach of children.

Packaging Film-coated tablets, 5 mg, 10 mg No. 14 or 28 in blisters.

Vacation category: Prescription.

Manufacturer Eli Lilly and Company, USA Indianapolis, Indiana 46285, USA

Indications

- to prevent thrombotic complications in patients with acute coronary syndrome undergoing percutaneous coronary intervention:

- patients with unstable angina or non-ST segment elevation myocardial infarction undergoing percutaneous coronary intervention;

- patients with ST-segment elevation myocardial infarction undergoing primary or delayed percutaneous coronary intervention.

- to prevent stent thrombosis in acute coronary syndrome.

Effient (Prasugrel) tab. 10mg No. 28 – Instructions

Compound

In addition to the active functional substance - prasugrel at a dose of 10 mg, the composition includes: microcrystalline cellulose, mannitol (E421), croscarmellose sodium, hypromellose (E464), magnesium stearate, lactose monohydrate, titanium dioxide (E171), triacetin (E1518), yellow oxide iron (E172), red iron oxide (E172), talc.

Release form

The tablets are beige in color and shaped like a double-headed arrow, marked “10 MG” on one side and “4759” on the other.

pharmachologic effect

Prasugrel is a thienopyrine derivative with antiaggregation activity.

It works by inhibiting one of the platelet activation pathways involved in the blood clotting process. On the surface of these structures there are purinergic receptors (P2Y1 and P2Y12), which are activated, including by ADP. The consequence of this process is a change in the shape of the plate, an increase in the concentration of calcium ions inside it and the expression of GPIIb / IIIa receptors that bind fibrinogen.

The prasugrel metabolite stably binds to the P2Y12 receptor, as a result of which one of the mechanisms of platelet activation is suppressed, disrupting the blood coagulation cascade. Decreased platelet function leads to reduced mortality from sudden cardiovascular events due to thrombotic complications in patients with atherosclerotic lesions.

Pharmacokinetics

Bioavailability exceeds 79%. Food does not change the total plasma concentration of the active metabolite. Peak concentrations occur 30 minutes after administration of the compound; this time may be extended if the substance is taken with food.

The main metabolite is 98% bound to plasma albumin.

Prasugrel in the form of inactive metabolites is largely excreted through the kidneys and 27% in feces.

Indications for use

Effient is used in patients who have had a heart attack, unstable angina, or have had surgery to remove blocked arteries in the heart. The medication reduces the risk of death from a heart attack or stroke, or the risk of the events occurring again, in these patients.

Contraindications

A limitation to the use of the compound is the occurrence of hypersensitivity reactions to the drug and severe liver failure or pathological bleeding. Effient should not be prescribed to people who have had a stroke or ischemic episodes.

Side effects

Frequent negative reactions are: anemia, hematoma, nosebleeds, gastrointestinal bleeding, skin rashes, bruises, hematuria, hematoma at the puncture site, bleeding at the injection site, bruise.

Drug interactions

Caution should be used when using Effient together with:

• clopidogrel (antiplatelet drug);
• warfarin (a drug that prevents blood clotting);
• non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, etoricoxib).

It is recommended to avoid excessive consumption of foods with anticoagulant or antiplatelet properties, such as garlic, ginger or blueberries, as these may increase the risk of bleeding.

Taking large amounts of ginkgo biloba or red sage may increase the chance of bleeding.

Application and dosage

The dosage schedule depends on the indications, the age of the patients and their clinical condition.

Effient can be given with or without food. Typically, a high loading dose is used (taking it on an empty stomach can accelerate the onset of clinical effect), and then the amount of drug consumed is reduced. Therapy should be continued for at least 12 months. The drug should be prescribed together with acetylsalicylic acid.

The usual loading dose is 60 mg, and the usual daily dose for adults is 10 mg.

Patients weighing up to 60 kg should also take maintenance doses not exceeding 5 mg per day; bleeding has been observed with the administration of larger amounts of the drug.

Overdose

Taking too high doses of the compound increases bleeding time and may promote bleeding.

special instructions

The use of the drug in people with a tendency to bleed should be carried out after assessing the benefits of treatment compared to the health risks in this group of people.

Users should be informed that in the event of bleeding (eg, due to injury), clotting time may be delayed, and people taking Effient should be cautioned to report any unusual bleeding, including duration, to their doctor.

The compound may cause angioedema. It is recommended to monitor patients for the development of hypersensitivity reactions, especially in those allergic to thienopyridine derivatives.

Use during pregnancy and breastfeeding

Effient is allowed to be used during pregnancy only if there is no safer alternative and the benefits of therapy for the expectant mother outweigh the possible risks to the health of the embryo/fetus.

Due to the underestimation of the impact of drug therapy on the baby's health, taking medication during breastfeeding is not recommended.

Impact on the ability to drive vehicles and operate machinery

There are no studies assessing the effect of Effint on psychomotor skills, however, taking into account the pharmacological mechanism and side effect profile, no harmful effects of this compound on driving or mechanical functioning should be expected.

Terms of sale

As prescribed by a doctor.

Storage conditions

It is important to store the drug in its original packaging and in a dry and cool place, away from children.

Dosage regimen

The drug is taken orally, regardless of food intake. It is unacceptable to break the tablet before taking it.

Prasugrel is started with a single loading dose of 60 mg. Then take a maintenance dose of 10 mg daily.

Patients with UA/NSTEMI who undergo coronary angiography within 48 hours of hospitalization should receive a loading dose only during percutaneous coronary intervention. Patients taking prasugrel should also take ASA (75-325 mg/day) daily.

In patients with ACS who have undergone percutaneous coronary intervention, premature discontinuation of therapy with any antiplatelet agent, including Effient®, may result in an increased risk of thrombosis, myocardial infarction, or death due to the underlying disease. It is recommended to continue treatment for up to 12 months, unless there are indications for discontinuation of the drug Effient®.

Patients weighing less than 60 kg

Start taking prasugrel with a single loading dose of 60 mg. Then take a daily maintenance dose of 5 mg. A maintenance dose of 10 mg is not recommended. This is due to increased exposure to the active metabolite of prasugrel in the blood and an increased risk of bleeding in patients weighing less than 60 kg compared to patients weighing 60 kg or more.

Use of Effient® in patients aged 75 years and older

, as a rule, is not recommended. If, after careful individual assessment by the attending physician of the balance of benefits and risks, treatment is considered necessary, in the age group of patients 75 years and older, prasugrel is started with a single loading dose of 60 mg, followed by a daily maintenance dose of 5 mg. Patients aged 75 years and older have a greater tendency to bleeding and higher exposure to the active metabolite of prasugrel (see sections "Special Instructions", "Side Effects", "Pharmacological Action", "Pharmacokinetics").

For patients with kidney failure, including patients with ESRD

, no dose adjustment is required. Experience with prasugrel in patients with renal failure is limited.

For patients with mild to moderate hepatic impairment (Child-Pugh class A and B)

no dose adjustment is required.
There is limited experience with the use of prasugrel in patients with mild to moderate hepatic impairment (see section "Precautions"). Effient® is contraindicated in patients with severe liver dysfunction (Child-Pugh class C)
(see section “Contraindications”).

The use of prasugrel is not recommended for children and adolescents under 18 years of age

, because Data on the effectiveness and safety of use in this group of patients are insufficient (see section “Contraindications”).

EFFECT TAB. P/P/O 10MG No. 28

Side effects identified in clinical trials (in the treatment of acute coronary syndromes)

Bleeding not associated with coronary artery bypass grafting (CABG)

Number of cases of complications and bleeding not related to CABG (% of patients)

:

aRecorded cases defined by TIMI classification criteria.

bVarious variations of standard therapy were used where appropriate. In the third phase of clinical trials, all patients also took acetylsalicylic acid.

cAny intracranial hemorrhage or any clinically significant bleeding associated with a decrease in hemoglobin? 5 g/dl.

Life-threatening is a subgroup of major bleeding according to TIMI, which also includes the types of bleeding presented below. Patients may be assigned to more than one group.

dIntracranial hemorrhage (ICH).

eClinically significant bleeding associated with a decrease in hemoglobin? 3 g/dl, but < 5 g/dl.

It was determined that when taking prasugrel at a daily maintenance dose of 10 mg or taking clopidogrel at a daily maintenance dose of 75 mg in patients with ACS who underwent percutaneous coronary angioplasty, patients weighing less than 60 kg have a greater risk of bleeding than patients weighing more than 60 kg.

When taking prasugrel at a daily maintenance dose of 10 mg or taking clopidogrel at a daily maintenance dose of 75 mg in patients with ACS who underwent percutaneous coronary angioplasty, the incidence of TIMI major and minor bleeding not associated with CABG in two age groups was as follows:

Other clinical studies

Patients with NSTEMI who received a loading dose of 30 mg at a median of 4 hours before coronary angiography and 30 mg during subsequent percutaneous coronary angioplasty had a higher risk of minor intraprocedural bleeding not related to CABG surgery and no additional benefit compared with patients receiving a loading dose of 60 mg during percutaneous coronary angioplasty.

The incidence of major and minor TIMI bleeding not related to CABG in patients within 7 days was as follows:

:

aVarious variations of standard therapy were used where appropriate. In the third phase of clinical trials, all patients also took acetylsalicylic acid.

bAny intracranial hemorrhage or any clinically significant bleeding associated with a decrease in hemoglobin ≥5 g/dl.

c Life-threatening is a subgroup of major bleeding according to TIMI, which also includes the types of bleeding presented below. Patients may be assigned to more than one group.

dIntracranial hemorrhage (ICH).

dClinically significant bleeding associated with a decrease in hemoglobin? 3 g/dL but < 5 g/dL.

Patients with ACS who did not undergo percutaneous coronary angioplasty took prasugrelil clopidogrel in combination with acetylsalicylic acid.

In patients over 75 years of age weighing less than 60 kg who took prasugrel at a maintenance dose of 5 mg per day for an average of 15 months (maximum 30 months), the incidence of TIMI major and minor bleeding not associated with CABG in two weight categories was as follows:

aMaintenance dose 5 mg.

bMaintenance dose 10 mg; in patients over 75 years of age, the maintenance dose is 5 mg.

cMaintenance dose 75 mg.

The incidence of major and minor TIMI bleeding not associated with CABG in two age groups was as follows:

aMaintenance dose 5 mg.

bMaintenance dose 10 mg; in patients weighing less than 60 kg, the maintenance dose is 5 mg.

cMaintenance dose 75 mg.

Bleeding associated with CABG

The incidence of major or minor bleeding according to the TIMI classification associated with CABG was 14.1% in patients taking prasugrel and 4.5% in patients taking clopidogrel. The high risk of bleeding in participants taking prasugrel continued until 7 days after the last dose of study drug.

Number of cases of complications and bleeding associated with CABG (% of patients):

Reported cases defined according to the TIM classification criteria The following is a summary of hemorrhagic and non-hemorrhagic adverse reactions and their frequency recorded during clinical trials.

Adverse reactions of a hemorrhagic nature

Visual disorders

Uncommon (?0.1% and <1%): hemorrhage into the eye.

Vascular disorders

Common(?>1% and <10%): hematoma.

Respiratory, thoracic and mediastinal disorders

Common (? 1% and <10%): epistaxis.

Uncommon (?0.1% and <1%): hemoptysis.

Gastrointestinal disorders

Common (?1% and <10%): gastrointestinal bleeding.

Uncommon (>0.1% and <1%): rectal bleeding, bleeding from the gums, bloody stools (hematochezia), retroperitoneal bleeding.

Skin and subcutaneous tissue disorders

Common (?1% and <10%): ecchymosis.

Renal and urinary tract disorders

Common (?1% and <10%): hematuria.

General and administration site disorders

Often (?1% and <10%): hematoma at the site of puncture of the vessel, bleeding at the puncture site.

Injuries, intoxications and complications of manipulations

Common (?1% and <10%): bruise.

Uncommon (>0.1% and <1%): subcutaneous hematoma, bleeding after the procedure.

Adverse reactions of a non-hemorrhagic nature

Blood and lymphatic system disorders

Common (?1% and <10%): anemia.

Rarely (?0.01% and <0.1%): thrombocytopenia (platelet count <50 x 109/l).

Skin and subcutaneous tissue disorders

Common (?1% and <10%): rash.

When using standard dosing regimens of prasugrel, patients who have previously had a stroke or transient ischemic attack (TIA) have been determined to have a greater risk of developing a stroke or TIA than patients without a history of these diseases:

*Intracranial hemorrhage (ICH).

Spontaneous adverse reactions

Hypersensitivity reactions, including angioedema, occurred with a frequency of >0.01% and <0.1%. Thrombocytopenic purpura occurred with a frequency of <0.01%.

Side effect

Side effects identified during clinical trials (in the treatment of acute coronary syndrome).

Bleeding not related to CABG

Incidence of complications and bleeding not related to CABG (% of patients):

a Recorded cases defined by TIMI classification criteria.

b Other standard therapy was used if necessary. In phase 3 clinical studies, all patients also took ASA according to the protocol.

c Any intracranial hemorrhage or bleeding with clinical manifestations, accompanied by a decrease in hemoglobin ≥5 g/dl.

d Life-threatening - a subgroup of major bleeding according to the TIMI classification, which, incl. includes the types of bleeding presented below. Patients may be assigned to more than one group.

d Intracranial hemorrhage (ICH).

e Bleeding with clinical manifestations, accompanied by a decrease in hemoglobin by ≥3 g/dl, but

Clinical studies show that when prasugrel is taken at a daily maintenance dose of 10 mg or clopidogrel is taken at a daily maintenance dose of 75 mg in patients with ACS undergoing PCI, patients weighing less than 60 kg have a greater risk of bleeding than patients weighing 60 kg or more.

When taking prasugrel at a daily maintenance dose of 10 mg or taking clopidogrel at a daily maintenance dose of 75 mg in patients with ACS who underwent PCI, the incidence of TIMI “major” and “minor” bleeding not associated with CABG in two age groups was as follows:

*Patients with ACS who underwent PCI.

**Patients with ACS who did not undergo PCI.

a 10 mg prasugrel; 5 mg prasugrel for weight

In patients with NSTEMI who received a loading dose of prasugrel 30 mg at a median of 4 hours before coronary angiography and 30 mg during subsequent PCI, there was a higher risk of non-CABG bleeding during the procedure and no additional benefit compared with patients taking a loading dose of 60 mg during PCI.

The incidence of major and minor bleeding according to the TIMI classification, not related to CABG, in patients within 7 days was as follows:

a Other standard therapy was used if necessary. In clinical studies, all patients also took ASA in accordance with the protocol.

b Any intracranial hemorrhage or bleeding with clinical manifestations, accompanied by a decrease in hemoglobin of ≥5 g/dL.

c Life-threatening - a subgroup of major bleeding according to the TIMI classification, which, incl. includes the types of bleeding presented below. Patients may be assigned to more than one group.

g VChK.

e Bleeding with clinical manifestations, accompanied by a decrease in hemoglobin by ≥3 g/dL, but

Patients with ACS who did not undergo PCI took prasugrel or clopidogrel in combination with ASA.

In patients over 75 years of age weighing less than 60 kg who took prasugrel at a maintenance dose of 5 mg/day for an average of 15 months (maximum 30 months), the incidence of TIMI major and minor bleeding not associated with CABG in two weight categories was the following:

a Maintenance dose 5 mg.

b Maintenance dose 10 mg; in patients over 75 years of age, the maintenance dose is 5 mg.

c Maintenance dose 75 mg.

The incidence of major and minor bleeding according to the TIMI classification, not related to CABG, in two age groups was as follows:

a Maintenance dose 5 mg.

b Maintenance dose 10 mg; in patients weighing less than 60 kg, the maintenance dose is 5 mg.

c Maintenance dose 75 mg.

Bleeding associated with CABG

In clinical studies, the incidence of TIMI major or minor bleeding associated with CABG was 14.1% in patients taking prasugrel and 4.5% in patients taking clopidogrel. The high risk of bleeding in patients taking prasugrel persisted for up to 7 days after the last dose of study drug.

Number of cases of complications and bleeding associated with CABG (% of patients):

a Confirmed cases defined by TIMI classification criteria.

The following is a summary of hemorrhagic and non-hemorrhagic adverse reactions and their frequency recorded during clinical trials.

Adverse reactions of a hemorrhagic nature

From the side of the organ of vision:

uncommon (≥0.1% and

From the side of blood vessels:

often (≥1% and

From the respiratory system, chest and mediastinal organs:

often (≥1% and

From the gastrointestinal tract:

often (≥1% and

For the skin and subcutaneous tissues:

often (≥1% and

From the kidneys and urinary tract:

often (≥1% and

General disorders and disorders at the injection site:

often (≥1% and

Injuries, intoxications and complications of manipulations:

often (≥1% and

Adverse reactions of a non-hemorrhagic nature

From the blood and lymphatic system:

often (≥1% and 9/l).

For the skin and subcutaneous tissues:

often (≥1% and

Clinical studies have demonstrated that, when using standard dosing regimens of prasugrel, patients with a previous history of stroke or TIA have a greater risk of developing stroke or TIA than patients without a history of these diseases:

Adverse reactions identified by spontaneous reporting method

Rarely - hypersensitivity reactions, including angioedema; very rarely - thrombotic thrombocytopenic purpura.

Contraindications for use Effient

- established hypersensitivity to prasugrel or to any component included in the drug;

- conditions with an increased risk of bleeding (pathological bleeding, for example, with peptic ulcer);

- history of transient ischemic attack (TIA) or stroke;

- severe liver failure (class C on the Child-Pugh scale);

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

— age up to 18 years;

- period of breastfeeding (see section “Pregnancy and lactation”);

- planned urgent CABG, due to the fact that this is associated with a higher risk of postoperative bleeding. When performing planned CABG, prior (7 days before the planned operation) withdrawal of prasugrel is recommended.

Carefully

Risk of bleeding:

Prasugrel should be administered with caution to patients:

- aged 75 years or older;

— with body weight less than 60 kg;

- with a predisposition to bleeding (for example, due to recent trauma, recent surgery, recent or repeated gastrointestinal bleeding, gastric or duodenal ulcers in the acute phase);

- with moderate liver failure or renal failure (including ESRD);

- while taking medications that may increase the risk of bleeding, including indirect anticoagulants and antiplatelet agents, nonsteroidal anti-inflammatory drugs (NSAIDs) and fibrinolytics;

- if the patient is scheduled for elective surgery and the antiplatelet effect is undesirable, it is necessary to stop taking prasugrel at least 7 days before surgery.

Prasugrel should be used with caution in patients with a history of thrombotic thrombocytopenic purpura (see section "Special Instructions").

Prasugrel should be taken with extreme caution and only under medical supervision in patients with a history of angioedema or other hypersensitivity reactions associated with taking thienopyridines.

Prasugrel should be used with caution during pregnancy due to the lack of clinical data (see section "Pregnancy and Lactation").

Use during pregnancy and breastfeeding Effient

Clinical studies have not been conducted in pregnant or lactating women.

Animal studies have not revealed any direct negative effects on pregnancy, embryonic development or postnatal development. Prasugrel should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether prasugrel is excreted into breast milk in humans. Animal studies have shown that prasugrel is excreted in breast milk. During breastfeeding, the use of the drug is not recommended.

Fertility

Prasugrel has no effect on fertility in male or female rats when administered orally at doses 240 times the recommended daily maintenance dose for humans (mg/m2).

Use for liver dysfunction Effient

For patients with moderate hepatic impairment, no dose adjustment is required (class A and B on the Child-Pugh scale).

Contraindicated in severe liver failure (class C on the Child-Pugh scale).

Use for impaired renal function Effient

For patients with renal impairment, including patients with end-stage renal failure (ESRD), no dose adjustment is required.

Use in children Effient

The use of the drug is contraindicated in people under 18 years of age.

Use in elderly patients Effient

Prasugrel should be used with caution in patients aged 75 years or older.

Special instructions Effient

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) may occur in less than 2 weeks after starting the drug. TTP is a serious disease that can be fatal and requires urgent treatment, including plasmapheresis. TTP is characterized by thrombocytopenia with hemorrhagic syndrome, neurological impairment, renal dysfunction and fever.

Surgical interventions

When planning surgical interventions or prescribing new medications, patients should inform their doctors, incl. dentists about the use of prasugrel.

If the patient requires elective surgery and the antiplatelet effect is undesirable, you should stop taking Effient® 7 days before surgery. Patients undergoing CABG may experience an increase in the frequency (3 times) and severity of bleeding within 7 days after discontinuation of prasugrel.

The benefits and risks of prasugrel should be carefully assessed in patients in whom coronary anatomy has not been determined and emergency CABG is a possibility.

Risk of bleeding

According to clinical studies, patients with NSTEMI who took a loading dose of prasugrel on average 4 hours before diagnostic coronary angiography increased the risk of major and minor bleeding compared with patients who took a loading dose of prasugrel during PCI. Patients should be warned about the possible increase in bleeding time while taking prasugrel (in combination with ASA) and the need to inform the doctor about any bleeding that occurs.

For risk factors for bleeding, see Contraindications and Precautions.

Hypersensitivity, including angioedema

Cases of hypersensitivity, including angioedema, have been reported in patients taking prasugrel, incl. in patients with a history of hypersensitivity reactions to other thienopyridines.

Lactose

Patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take Effient®.

Impact on the ability to drive vehicles and operate machinery

The effect of prasugrel on the ability to drive vehicles and machines has not been established.

Overdose of Effient

Symptoms:

Possible increase in bleeding time and associated complications.

Treatment:

There is no information on the reversibility of the pharmacological effect of prasugrel, however, if urgent reduction of bleeding time is required, transfusion of platelets and/or other blood products can be performed.

Drug interactions Effient

Warfarin

Due to the possibility of an increased risk of bleeding, the simultaneous use of warfarin and prasugrel should be carried out with extreme caution.

NSAIDs

Prasugrel has not been studied during chronic NSAID therapy. Due to the possibility of an increased risk of bleeding, the use of prasugrel during chronic therapy with NSAIDs (including COX-2 inhibitors) should be carried out with extreme caution.

Medicines metabolized by the CYP2B6 isoenzyme

Prasugrel is a weak inhibitor of the CYP2B6 isoenzyme. In healthy subjects, prasugrel reduced the exposure of hydroxybupropion, a metabolite of bupropion formed by the CYP2B6 isoenzyme, by 23%. This effect may be clinically significant only when prasugrel is used in conjunction with drugs that have a narrow therapeutic window and are metabolized exclusively by the CYP2B6 isoenzyme (for example, cyclophosphamide or efavirenz).

Other types of combined use of drugs

Prasugrel can be used concomitantly with drugs that are metabolized by cytochrome P450 isoenzymes, including statins, or with drugs that are inducers or inhibitors of cytochrome P450 isoenzymes.

Prasugrel can also be used concomitantly with ASA, heparin, digoxin and drugs that increase gastric pH, including proton pump inhibitors, and histamine H2 receptor blockers.

Acetylsalicylic acid

Effient® should be taken together with acetylsalicylic acid. Although there may be an increased risk of bleeding due to pharmacodynamic interactions with ASA, the efficacy and safety of prasugrel have been demonstrated in patients taking prasugrel with ASA.

Heparin

A single intravenous bolus dose of unfractionated heparin (100 units/kg) does not significantly alter prasugrel-mediated inhibition of platelet aggregation. Similarly, prasugrel does not significantly alter the effect of heparin on coagulation. Thus, both drugs can be used together. An increased risk of bleeding is possible with simultaneous use of the drug Effient® with heparin.

Conditions and periods of storage of Effient

The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life: 2 years. Do not use after expiration date.

Effient®

Side effects identified in clinical trials (in the treatment of acute coronary syndromes)

Bleeding not associated with coronary artery bypass grafting (CABG)

Number of cases of complications and bleeding not related to CABG (% of patients):

aRecorded cases defined by TIMI classification criteria.

bVarious variations of standard therapy were used where appropriate. In the third phase of clinical trials, all patients also took acetylsalicylic acid.

c Any intracranial hemorrhage or any clinically significant bleeding associated with a decrease in hemoglobin ≥ 5 g/dL.

d Life-threatening - a subgroup of major bleeding according to TIMI, which also includes the types of bleeding presented below. Patients may be assigned to more than one group.

d Intracranial hemorrhage (ICH).

f Clinically significant bleeding associated with a decrease in hemoglobin ≥ 3 g/dL but < 5 g/dL.

It was determined that when taking prasugrel at a daily maintenance dose of 10 mg or taking clopidogrel at a daily maintenance dose of 75 mg in patients with ACS who underwent percutaneous coronary angioplasty, patients weighing less than 60 kg have a greater risk of bleeding than patients weighing more than 60 kg.

When taking prasugrel at a daily maintenance dose of 10 mg or taking clopidogrel at a daily maintenance dose of 75 mg in patients with ACS who underwent percutaneous coronary angioplasty, the incidence of TIMI major and minor bleeding not associated with CABG in two age groups was as follows:

Other clinical studies

Patients with NSTEMI who received a loading dose of 30 mg at a median of 4 hours before coronary angiography and 30 mg during subsequent percutaneous coronary angioplasty had a higher risk of minor intraprocedural bleeding not related to CABG surgery and no additional benefit compared with patients receiving a loading dose of 60 mg during percutaneous coronary angioplasty.

The TIMI major and minor bleeding rates not related to CABG in patients over 7 days were as follows:

a Variations of standard therapy were used where appropriate. In the third phase of clinical trials, all patients also took acetylsalicylic acid.

b Any intracranial hemorrhage or any clinically significant bleeding associated with a decrease in hemoglobin ≥5 g/dL.

c Life-threatening is a subgroup of major bleeding according to TIMI, which also includes the types of bleeding presented below. Patients may be assigned to more than one group.

d Intracranial hemorrhage (ICH).

d Clinically significant bleeding associated with a decrease in hemoglobin ≥ 3 g/dL but < 5 g/dL.

Patients with ACS who did not undergo percutaneous coronary angioplasty took prasugrel or clopidogrel in combination with acetylsalicylic acid.

In patients over 75 years of age weighing less than 60 kg who took prasugrel at a maintenance dose of 5 mg per day for an average of 15 months (maximum 30 months), the incidence of TIMI major and minor bleeding not related to CABG in two weight categories was next:

a Maintenance dose 5 mg.

b Maintenance dose 10 mg; in patients over 75 years of age, the maintenance dose is 5 mg.

c Maintenance dose 75 mg.

The frequency of major and minor bleeding according to TIMI, not associated with CABG, in two age groups was as follows:

a Maintenance dose 5 mg.

b Maintenance dose 10 mg; in patients weighing less than 60 kg, the maintenance dose is 5 mg.

c Maintenance dose 75 mg.

Bleeding associated with CABG

The incidence of TIMI major or minor bleeding associated with CABG was 14.1% in patients taking prasugrel and 4.5% in patients taking clopidogrel. The high risk of bleeding in participants taking prasugrel continued until 7 days after the last dose of study drug.

Number of cases of complications and bleeding associated with CABG (% of patients):

Reported cases defined by TIMI classification criteria The following is a summary of hemorrhagic and non-haemorrhagic adverse reactions and their frequency recorded during clinical trials.

Adverse reactions of a hemorrhagic nature

Visual disorders

Uncommon (≥0.1% and <1%): hemorrhage into the eye.

Vascular disorders

Common (≥>1% and <10%): hematoma.

Respiratory, thoracic and mediastinal disorders

Common (≥ 1% and <10%): epistaxis.

Uncommon (≥0.1% and <1%): hemoptysis.

Gastrointestinal disorders

Common (≥1% and <10%): gastrointestinal bleeding.

Uncommon (>0.1% and <1%): rectal bleeding, bleeding from the gums, bloody stools (hematochezia), retroperitoneal bleeding.

Skin and subcutaneous tissue disorders

Common (≥1% and <10%): ecchymosis.

Renal and urinary tract disorders

Common (≥1% and <10%): hematuria.

General and administration site disorders

Often (≥1% and <10%): hematoma at the site of vascular puncture, bleeding at the puncture site.

Injuries, intoxications and complications of manipulations

Common (≥1% and <10%): bruise.

Uncommon (>0.1% and <1%): subcutaneous hematoma, bleeding after the procedure.

Adverse reactions of a non-hemorrhagic nature

Blood and lymphatic system disorders

Common (≥1% and <10%): anemia.

Rarely (≥0.01% and <0.1%): thrombocytopenia (platelet count <50 x 109/l).

Skin and subcutaneous tissue disorders

Common (≥1% and <10%): rash.

When using standard dosing regimens of prasugrel, patients who have previously had a stroke or transient ischemic attack (TIA) have been determined to have a greater risk of developing a stroke or TIA than patients without a history of these diseases:

*Intracranial hemorrhage (ICH).

Spontaneous adverse reactions

Hypersensitivity reactions, including angioedema, occurred with a frequency of >0.01% and <0.1%. Thrombocytopenic purpura occurred with a frequency of <0.01%.