Effient pills 10mg, 28pcs

Composition

Each film-coated tablet contains:

Active ingredient:  prasugrel hydrochloride 10.98 mg, corresponds to prasugrel (base) 10.00 mg;

excipients:  mannitol 67.21 mg, hypromellose 5.285 mg, croscarmellose sodium 11.00 mg, microcrystalline cellulose 78.75 mg, magnesium stearate 1.58 mg; shell:  opadray II beige (lactose monohydrate 2.10 mg, hypromellose 3.85 mg, titanium dioxide 1.58 mg, triacetin 0.70 mg, iron oxide yellow dye 0.46 mg, iron oxide red dye 0.06 mg) 8.75 mg, talc up to 0.001 mg

Pharmacological action

Pharmacotherapy group

Antiplatelet agent

KodATH:  B 01 AC 22

Pharmacological properties

Pharmacodynamics

Mechanism of action

The antiplatelet agent prasugrel is an antagonist of the P2Y12 class of adenosine diphosphate (ADP) receptors and inhibits platelet activation and aggregation. Since platelets are involved in the development of atherosclerotic complications, inhibiting 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 is 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 per day (after the previous loading dose of the drug), that is, in an average equilibrium state, the suppression of platelet aggregation is about 70%.

Platelet aggregation after the end of prasugrel therapy gradually returns to the baseline values: within 7-9 days after a single dose of prasugrel 60 mg and within 5 days after discontinuation of 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 in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (4KB), 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 during 4KB resulted in a similar increase in platelet aggregation inhibition over 72 hours.

Efficiency and safety

In a clinical trial involving ACS patients at risk of developing unstable angina (NS)/ non-ST-segment elevation myocardial infarction (ST-PD MI) and patients with ST-segment elevation myocardial infarction (ST-SP MI) who underwent 4KB, prasugrel and clopidogrel, taken with acetylsalicylic acid (ASA) and other medications, were compared according to treatment standards.

At the same time, patients taking prasugrel (60 mg loading dose, followed by a daily dose of 10 mg) or clopidogrel (300 mg loading dose, followed by a daily dose of 75 mg) were treated for an average of 14.5 months with follow-up for at least 6 months. Patients received ASA (75 to 325 mg once daily). The effectiveness criterion is the time until the first case 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 NS/MI of ST PD and ST SP MI) was based on the demonstration of statistical superiority of prasugrel in comparison with clopidogrel in the group of patients with NS/MI of ST PD (p Effient® is more effective than clopidogrel in reducing the incidence of the primary combined endpoint as well as the incidence of secondary endpoints, including stent thrombosis. The benefit of prasugrel is observed during the first 3 days and persists until the end of the study. Superior efficacy is accompanied by an increase in the frequency of “large” bleeding (see sections “With caution” and “Side effects”). The effectiveness of prasugrel does not depend on age, gender, body weight, geographical region, concomitant therapy, including heparin, bivalirudin, intravenous GPIIb/IIIa inhibitors, lipid-lowering drugs, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, ASA dosage (from 75 to 325 mg once a day).

The benefits are mainly manifested in a significant reduction in the frequency of non-fatal myocardial infarction. Patients with diabetes also have a significant reduction in the incidence of primary and all secondary combined endpoints (non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes). The observed benefits of prasugrel are less pronounced in patients 75 years and older than in patients younger than 75 years (see sections “Pharmacokinetics”, “Dosage and use”, ” With caution “and”Side effects”). For patients with diabetes, STEMI, an increased risk of stent thrombosis, or relapses of the disease included in the group of patients 75 years and older, the advantage of prasugrel is more pronounced. In the entire population of patients with ACS, analysis for each secondary endpoint showed a significant advantage of prasugrel over clopidogrel in terms of the frequency of events such as detected or possible stent thrombosis at the end of the study, death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, emergency revascularization of the target vessel within 30 days or repeated hospitalization due to coronary-ischemic events before the end of the study.

Analysis of the incidence of all-cause deaths did not show any significant difference between prasugrel and clopidogrel in the population of all ACS patients. Prasugrel was associated with a 50% reduction in stent thrombosis during the 15-month follow-up period for both uncoated metal stents and drug-coated stents.

Despite the increase in the number of hemorrhages associated with prasugrel therapy, analysis of the combined endpoint of death from any cause, non-fatal myocardial infarction, non-fatal stroke, and non-coronary artery bypass grafting (CABG) “large” bleeding according to the TIMI classification shows the advantage of Effient® in comparison with clopidogrel.

Pharmacokinetics

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

Absorption rate

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 use. The AUC of the active metabolite increases in direct proportion to the therapeutic dose of the drug.

In healthy volunteers, fatty and high-calorie foods do not affect the AUC of the active metabolite, but the maximum concentration (CW) decreases by 49%, and the time to reach Cmax (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 the section “Dosage and use”).

Distribution

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

Metabolism

Prasugrel is not detected in plasma after oral use. Prasugrel is rapidly hydrolyzed in the gut to thiolactone, which is then converted to the active metabolite mainly by cytochrome P450 isoenzymes such as CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19 isoenzymes. 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 atherosclerosis, and patients who underwent 4KB who took Effient®, there was no effect of genetic variations of the CYP2B6, CYP2C9, CYP2C19, or CYP3A5 isoenzymes on the pharmacokinetic parameters of prasugrel or inhibition of platelet aggregation.

Deduction

Approximately 68% of prasugrel is excreted in the urine and about 27% in the faeces as inactive metabolites. The half-life of the active metabolite is about 7.4 hours (2 to 15 hours interval).

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 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 and older due to the potential risk of bleeding in this population (see sections “Dosage and use” and “With caution”). In a study involving patients with a stable course of atherosclerotic process, the AUC of the active metabolite in a population of patients 75 years and older taking 5 mg of prasugrel is approximately half as low as in patients younger than 65 years taking 10 mg of prasugrel, while only in patients taking 5 mg the antiplatelet effect of prasugrel decreases.

Body weight.

The AUC of the active metabolite of prasugrel is approximately 30 to 40%o higher in healthy volunteers and patients with a body weight of less than 60 kg compared to those with a body weight of 60 kg or more.

Gender.

In healthy volunteers and patients, the pharmacokinetics of prasugrel did not differ in men and women.

Ethnicity.

In clinical pharmacological studies, the AUC of the active metabolite (taking into account body weight) is approximately 19% higher in people of Chinese, Japanese and Korean nationality compared to representatives of the Caucasian race. There were no differences between people of Chinese, Japanese, and Korean nationality. Representatives of the Black race and people of Latin American origin have a comparable exposure to those of the Caucasian race. No dose adjustment based on ethnicity is required.

Kidney failure.

For patients with renal insufficiency, 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 insufficiency (glomerular filtration rate 30-49 ml / min/1.73 m2 of body surface area) and in healthy volunteers. The inhibition of platelet aggregation caused by prasugrel was also comparable in ESRD patients requiring hemodialysis and in healthy volunteers, despite the fact that in ESRD patients, the Ctax and AUC of the active metabolite decreased by 51% and 42%, respectively.

Liver failure.

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

Children and adolescents under the age of 18.

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

Indications

• Prasugrel is prescribed 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.

• Prasugrel is prescribed to prevent stent thrombosis in acute coronary syndrome.

Contraindications

• Established hypersensitivity to prasugrel or to any component that is part of the drug.
• Conditions with an increased risk of bleeding (pathological bleeding in the active phase, for example, with a peptic ulcer).
• A history of transient ischemic attack (TIA) or stroke.
• Severe hepatic insufficiency (Child-Pugh class C).
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
• Under 18 years of age.
• Breast-feeding period (see the section “Use during pregnancy and lactation”).
• Planned urgent CABG due to the fact that it is associated with a higher risk
• of postoperative bleeding. When performing planned CABG
• , it is recommended to cancel prasugrel before (7 days before the planned operation)
• .

Be careful

about the risk of bleeding:

• Prasugrel should be administered with caution to patients:
• at the age of 75 years and older
• with body weight less than 60 kg;
• with a predisposition to bleeding (e. g., recent trauma, recent surgery, recent or recurrent gastrointestinal bleeding, stomach ulcers or duodenal ulcers in phase of exacerbation);
• with moderate hepatic impairment or renal failure (including ESRD);
• at the same time taking drugs that may increase the risk of bleeding, including indirect anticoagulants and antiplatelet agents, nonsteroidal anti-inflammatory drugs (NSAIDs) and fibrinolytic;
• if the patient is assigned to elective surgery and antiplatelet effect is undesirable, it is necessary to stop reception prasugrel not less than 7 days before the operation.

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 the use of thienopyridines. Prasugrel should be used with caution during pregnancy due to the lack of clinical data (see section “Use during pregnancy and lactation”).

Side effects

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

Non-CABG bleeding

Rate of complications and non-CABG bleedingia (% of patients):

Adverse reactions	Prasugrel+ASCb(N=6741)	Clopidogrelb+ ASA (N=6716)
“Large” bleeding according to the TIMIb classification	2.2	1.7
Life-threatening threats, all of them:	1.3	0.8
Including:
– Fatal	0.3	0.1
-ICCd with clinical manifestations	0.3	0.3
-Requiring inotropic drugs	0.3	0.1
-Requiring surgery	0.3	0.3
-Requiring blood transfusion (≥4 units)	0.7	0.5
-” Small ” bleeding according to	TIMIe 2.4	1.9

a Recorded cases determined by the TIMI classification criteria.

b If necessary, another standard therapy was used. In phase 3 clinical trials, all patients also received ASA in accordance with

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

g Life-threatening – a subgroup of major bleeding events according to the TIMI classification, which also includes the types of bleeding presented below. Patients can be assigned to more than one group.

d Intracranial hemorrhage (ICH).

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

Clinical studies show 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 PCI, patients with a body weight of less than 60 kg have a greater risk of bleeding than patients with a body weight of 60 kg or more.

Body weight	Prasugrel	Clopidogrel
<60 kg	10.1% (fatal 0%)	6.5% (fatal 0.3%)
≥60 kg	4.2% (fatal 0.3%)	3.3% (fatal 0.1%)

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 frequency of” large “and” small ” TIMI bleeding not associated with CABG in the two age groups was as follows:

Age group	Prasugrel 10 mg	Clopidogrel 75 mg
≥75 years*	9.0% (fatal 1.0%)	6.9% (fatal 0.1%)
<75 years*	3.8% (fatal 0.2%)	2.9% (fatal 0.1%)
<75 years* *	2.0% (fatal 0.1%)and	1.3% (fatal 0.1%)
	Prasugrel 5 mg	Clopidogrel 75 mg
≥75 years* *	2.6% (fatal 0.3%)	3.0% (fatal 0.5%)

* Patients with ACS who underwent PCI.

* * Patients with ACS who did not undergo PCI.

a 10 mg prasugrel; 5 mg prasugrel at weight <60 kg.

In patients with BP ST THEM, taking the load dose was 30 mg prasugrel on average for 4 h before coronary angiography and 30 mg during the subsequent PCI, during the procedure had a high risk of bleeding not related to CABG, and no additional benefits compared with patients taking a load dose of 60 mg during PCI.

The frequency of major and minor bleeding according to the classification TIMI non-CABG patients during the 7 days following:

Adverse reactions	Prasugrel before coronary angiographia (%)	Prasugrel during percutaneous coronary intervention (%)
“Large” bleeding according to the TIMIb classification	1.3	0.5
Life-threatening, vsev	0.8	0.2
Including:
– Fatal	0.1	0.0
-HSCc with clinical manifestations	0.0	0.0
-Requiring inotropic drugs	0.3	0.2
-Requiring surgery	0.4	0.1
-Requiring blood transfusion (≥ 4 units)	0.3	0.1
-” Small ” bleeding according to TIMId	1.7	0.6

a If necessary, another standard therapy was used. In clinical trials, all patients also received ASA. b in accordance with the protocol.

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

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

g of the Cheka.

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

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

In patients over 75 years of age with a body weight of 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 frequency of large and small bleeding according to the TIMI classification, not associated with CABG in the two weight categories was as follows:

Body weight	Prasugrel	Clopidogrel
<60 kg	1.4% (fatal 0.1%)a	2.2% (fatal 0.3%)
c≥60 kg	2.2% (fatal 0.2%) b	1.6% (fatal 0.2%)

c a Maintenance dose 5 mg

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

. in The maintenance dose was 75 mg

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

Age group	Prasugrel	Clopidogrel
≥75 years	2.6% (fatal 0.3%) a	3.0% (fatal 0.5%)
c<75 years	2.0% (fatal 0.1%) b	1.3% (fatal 0.1%)

c a Maintenance dose 5 mg

. b Maintenance dose of 10 mg; in patients with a body weight of less than 60 kg, maintenance dose of 5 mg

. in The maintenance dose is 75 mg.

CABG-related bleeding

In clinical trials, the incidence of major or minor CABG-related bleeding according to the TIMI classification was 14.1% in patients taking prasugrel and 4.5% in patients taking clopidogrel. A high risk of bleeding in patients taking prasugrel persisted up to 7 days after the last dose of the study drug was taken.

Number of CABG-related complications and bleedingsa (% of patients):

	Prasugrel	Clopidogrel
” Large “or” small “bleeding according to TIMI classification	14.1	4.5
” Large ” bleeding according to TIMI classification	11.3	3.6
Fatal	0.9	0
Repeated operation	3.8	0.5
Transfusion ≥ 5 units of blood	6.6	2.2
Brain hemorrhage	0	0
” Minor ” bleeding according to the TIMI classification	2.8	0.9

a Confirmed cases identified by the TIMI classification criteria.

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

Adverse reactions of a hemorrhagic nature

From the side of the visual organ: infrequently (≥0.1% and

From the side of blood vessels: frequently (≥1% and

Respiratory, thoracic and mediastinal disorders: frequent (≥1% and <10%) nosebleeds; infrequent (≥0.1% and < 10%) nosebleeds.

From the gastrointestinal tract: common (≥1% and <10%): gastrointestinal bleeding; infrequent (≥0.1% and < 10%).

Skin and subcutaneous tissue disorders: frequently (≥1% and

From the side of the kidneys and urinary tract: frequently (≥1% and

General disorders and disorders at the injection site: frequently (≥1% and

Injuries, intoxications, and manipulation complications: often (≥1% and <10%) – bruise; infrequently (≥0.1% and < 10%) – bruise.

Non-hemorrhagic adverse reactions

Blood and lymphatic system disorders: often (≥1% and <10%) – anemia; rarely (≥0.01% and < 10%) – anemia.

Skin and subcutaneous tissue disorders: frequently (≥1% and

Clinical studies have shown that when using standard prasugrel dosage regimens, patients who have previously had a stroke or TIA have a greater risk of developing a stroke or TIA than patients without a history of these diseases:

History of TIA or stroke	Prasugrel	Clopidogrel
Yes	6.5% (2.3% CHEKA)	1.2% (0% CHEKA)
No	0.9% (0.2% CHEKA)	1.0% (0.3% CHEKA)

Adverse reactions detected by the spontaneous message collection method

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

Interaction

Warfarin

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

NSAIDs

Prasugrel has not been studied in combination with continuous NSAID therapy. Due to the possibility of an increased risk of bleeding, prasugrel should be used with extreme caution in combination with non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors).

Drugs that are metabolized by the CYP2B6 isoenzyme

Prasugrel is a weak inhibitor of the CYP2B6 isoenzyme. In healthy subjects, prasugrel reduced exposure to hydroxybupropion, a metabolite of bupropion formed by the CYP2B6 isoenzyme, by 23%. This effect can be clinically pronounced only when prasugrel is used in combination 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 drug use

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 the pH of gastric juice, including proton pump inhibitors, and histamine_H2receptor blockers.

Acetylsalicylic Acid

Effient® should be taken together with acetylsalicylic acid. Although the pharmacodynamic interaction with ASA may increase the risk of bleeding, the efficacy and safety of prasugrel has been demonstrated in patients taking prasugrel together with ASA.

Heparin

A single intravenous bolus dose of unfractionated heparin (100 U / kg) did 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 the simultaneous use of the drug Effient® with heparin.

How to take, course of use and dosage

It 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 daily maintenance dose of 10 mg.

Patients with NS / MI of ST PD who undergo coronary angiography within 48 hours of hospitalization should take the loading dose only during percutaneous coronary intervention. Patients taking prasugrel should also take ASA daily (75-325 mg per day).

In patients with ACS who have undergone percutaneous coronary intervention, premature discontinuation of 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 Effient®.

Patients with a body weight of less than 60 kg: Prasugrel is started with a single loading dose of 60 mg. Next, take a daily maintenance dose of 5 mg. A maintenance dose of 10 mg is not recommended. This is due to increased exposure of the active metabolite of prasugrel in the blood and an increased risk of bleeding in patients with a body weight of less than 60 kg compared to patients with a body weight of 60 kg or more.

Patients aged 75 years or older: The use of the drug Effient® in patients aged 75 years and older is generally not recommended. If, after careful individual assessment by the attending physician of the benefit-risk ratio, 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, then a daily maintenance dose of 5 mg is prescribed. Patients aged 75 and older have a greater tendency to bleed and a higher exposure to the active metabolite of prasugrel (see sections “Special instructions”, “Side effects”, “Pharmacodynamics”, “Pharmacokinetics”).

Patients with renal insufficiency: No dose adjustment is required for patients with renal insufficiency, including ESRD patients. Experience with prasugrel in patients with renal insufficiency is limited.

Patients with hepatic insufficiency: No dose adjustment is required for patients with mild to moderate hepatic insufficiency (Child-Pugh class A and B). There is limited experience with prasugrel in patients with mild to moderate hepatic impairment (see section “With caution”). Effient® is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) (see section “Contraindications”).

Children and adolescents under 18 years of age: The use of prasugrel is not recommended for children and adolescents, as data on the effectiveness and safety of use in this group of patients are insufficient (see the section “Contraindications”).

Overdose

Symptoms: it is possible to increase the bleeding time and related complications.

Treatment: There is no information on the reversibility of the pharmacological effect of prasugrel, however, if an urgent reduction in bleeding time is required, a transfusion of platelet mass and/or other blood products can be performed.

Functional features

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 in the individual patient (19%). The pharmacokinetic parameters of prasugrel are similar in healthy volunteers, patients with a stable course of atherosclerotic process, 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 use. 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 did not affect the AUC of the active metabolite, but with_max decreases by 49%, and tmax increases from 0.5 h to 1.5 h. Taking a loading dose of the drug Effient® fasting can provide a faster onset of action (see the section “Dosage regimen”).

Distribution

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

Metabolism

Prasugrel is not detected in plasma after oral use. Prasugrel is rapidly hydrolyzed in the gut to thiolactone, which is then converted to the active metabolite mainly by cytochrome P450 isoenzymes such as CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19 isoenzymes. 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 atherosclerosis, and patients undergoing PCI treated with Effient®, there was no effect of genetic variations of the CYP2B6, CYP2C9, CYP2C19, or CYP3A5 isoenzymes on the pharmacokinetic parameters of prasugrel or inhibition of platelet aggregation.

Deduction

Approximately 68% of prasugrel is excreted in the urine and about 27% in the faeces as inactive metabolites. T_1/2 The duration 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 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 and older due to the potential risk of bleeding in this population (see sections “Dosage regimen” and “With caution”). In a study involving patients with a stable course of atherosclerotic process, the AUC of the active metabolite in a population of patients 75 years and older taking 5 mg of prasugrel is approximately half as low as in patients younger than 65 years of age taking 10 mg of prasugrel, while only in patients taking 5 mg, the antiplatelet effect of prasugrel decreases.

Body weight. The AUC of the active metabolite of prasugrel is approximately 30-40% higher in healthy volunteers and patients with a body weight of less than 60 kg compared to those with a body weight of 60 kg or more.

Gender. In healthy volunteers and patients, the pharmacokinetics of prasugrel did not differ in men and women.

Ethnicity. In clinical pharmacological studies, the AUC of the active metabolite (taking into account body weight) is approximately 19% higher in people of Chinese, Japanese and Korean nationality compared to representatives of the Caucasian race. There were no differences between people of Chinese, Japanese, and Korean nationality. Representatives of the Black race and people of Latin American origin have a comparable exposure to those of the Caucasian race. No dose adjustment based on ethnicity is required.

Kidney failure. For patients with renal insufficiency, 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 insufficiency (GFR 30-49 ml / min/1.73 m2 of body surface area) and in healthy volunteers. The inhibition of platelet aggregation induced by prasugrel was also comparable in ESRD patients requiring hemodialysis and in healthy volunteers, despite the fact that ESRD patients with_max and AUC of the active metabolite decreased by 51% and 42%, respectively.

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

Children and adolescents under the age of 18. The pharmacokinetics and pharmacodynamics of prasugrel in children and adolescents have not been studied.

Special instructions

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) may occur less than 2 weeks after starting the drug. TTP is a serious disease that can lead to death and requires urgent treatment, including plasmapheresis. TTP is characterized by thrombocytopenia with hemorrhagic syndrome, neurological disorders, impaired renal function, and fever.

Surgical interventions

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

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

The benefits and risks of using prasugrel should be carefully evaluated for patients who have not had their coronary anatomy determined and may need emergency CABG.

Risk of bleeding

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

For risk factors for bleeding, see the section “Contraindications” and “With caution”.

Hypersensitivity, including angioedema

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

Lactose

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

Influence on the ability to drive motor vehicles and manage mechanisms

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

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

Shelf

life is 2 years. Do not use after the expiration date.

Active ingredient

Prasugrel

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Thrombosis prevention