Effient, 10 mg 28 pcs

Pharmacotherapeutic group

Antiaggregant drug

CodeATH: B01AC22

Pharmacological properties

Pharmacodynamics

Mechanism of action

The antiplatelet agent prasugrel is a P2Y12 class receptor antagonist to adenosine diphosphate (ADP) and inhibits platelet activation and aggregation. Because platelets are involved in the development of atherosclerotic complications, inhibiting their function helps to 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 arterial lesions, 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 preceding loading dose of the drug), that is, in the average equilibrium state, inhibition of platelet aggregation is about 70%.

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

Transfer data

Transfer to prasugrel after treatment with clopidogrel at a daily dose of 75 mg for 10 days showed similar or greater inhibition of platelet aggregation. In a study in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (4KB), switching from an initial loading dose of 600 mg of clopidogrel or placebo taken before coronarography to a 60 mg loading dose of prasugrel taken during 4KB resulted in a similar increase in platelet aggregation inhibition within 72 hours.

Efficacy and safety

. In a clinical trial involving ACS patients at risk for unstable angina (UA)/myocardial infarction without ST-segment elevation (STEMI) and patients with ST-segment elevation myocardial infarction (STEMI) treated with 4KB, prasugrel and clopidogrel taken with acetylsalicylic acid (ASA) and other medications were compared according to treatment standards.

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 and followed up for at least 6 months. Patients received ASA (75 to 325 mg once daily). The criterion for efficacy was time to first nonfatal heart attack, nonfatal stroke, or death from a cardiovascular cause.

The analysis of the combined endpoint in the entire population of patients with ACS (combined population with NS/IM BP ST and SP ST MI) was based on demonstrating the statistical superiority of prasugrel versus clopidogrel in the group of patients with NS/IM BP ST (p < 0.05). Effient® shows higher efficacy compared to clopidogrel in reducing the incidence of primary combined endpoints as well as the incidence of secondary endpoints, including stent thrombosis. The advantage of prasugrel is observed within the first 3 days and persists until the end of the study. Superior efficacy is accompanied by an increased incidence of “major” bleeding (see sections “Caution” and “Side effects”). Efficacy of prasugrel is independent of age, sex, body weight, geographic region, concomitant therapy, including heparin, bivalirudin, intravenous GPIIb/IIIa inhibitors, hypolipidemic drugs, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, ASA dosage (75 to 325 mg once daily).

The benefits are mainly manifested by a significant reduction in the incidence of nonfatal myocardial infarction. In diabetic patients, there is also a significant reduction in the incidence of primary and all secondary combined end points (nonfatal myocardial infarction, nonfatal stroke or death from a cardiovascular cause). The observed benefits of prasugrel are less pronounced in patients 75 years of age or older than in patients younger than 75 years of age (see sections “Pharmacokinetics,” “Dosage and administration,” “Caution,” and “Side effects”). For patients with diabetes, STEMI, increased risk of stent thrombosis or recurrent disease, included in the group of patients 75 years and older, the benefit 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 the incidence of events such as detected or possible stent thrombosis at the end of the study, death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, emergency target vessel revascularization within 30 days or repeated hospitalization due to coronary-ischemic events before the study end.

An analysis of all-cause mortality rates showed no significant difference between prasugrel and clopidogrel in the population of all patients with ACS. Prasugrel use was associated with a 50% reduction in stent thrombosis over a 15-month follow-up period for both uncoated metal stents and drug-eluting stents.

Despite an increase in bleeding on prasugrel therapy, analysis of the combined endpoint of death from any cause, nonfatal myocardial infarction, nonfatal stroke and nonaortocoronary bypass (ACB) “major” TIMI bleeding shows a benefit of Effient® compared to clopidogrel.

Pharmacokinetics

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

Absorption

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

In healthy volunteers, fatty and high-calorie food has no effect on AUC of active metabolite, but maximum concentration (CW) is decreased by 49%, and time to reach Cmax (Tmax) is increased from 0.5 hours to 1.5 hours. Loading doses of Effient® on an empty stomach may provide a faster onset of action (see section “Dosage and administration”).

Distribution

The binding of the active metabolite 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 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 cysteine conjugation.

In healthy volunteers, patients with stable atherosclerotic disease, and 4KB patients taking Effient®, no effect of genetic variations in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 isoenzymes on prasugrel pharmacokinetic parameters or platelet aggregation suppression was observed.

Elimation

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

Particular 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 is independent of patient age. 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 because of the potential risk of bleeding in this population (see sections “Dosage and administration” and “Caution”). In a study involving patients with stable atherosclerotic disease, the AUC of the active metabolite in a population of patients 75 years and older taking 5 mg prasugrel was approximately half that of patients younger than 65 years taking 10 mg prasugrel, with only the antiaggregant effect of prasugrel reduced in patients taking 5 mg.

Body weight.

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

Performance.

In healthy volunteers and patients, prasugrel pharmacokinetic parameters do not differ between males and females.

Ethnicity.

In clinical pharmacology studies, the AUC of the active metabolite (adjusted for body weight) was approximately 19%) higher in individuals of Chinese, Japanese, and Korean ethnicity compared to individuals of Caucasian race. No differences were found between Chinese, Japanese, and Korean individuals. Exposure was comparable to that of Caucasians in the Negro race and Hispanics. There is no need to adjust the dose taking into account ethnicity.

Renal insufficiency.

Dose adjustment is not required for patients with renal impairment, including patients with terminal renal failure (TKF). The pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation are similar in patients with moderate renal failure (glomerular filtration rate 30 – 49 ml/min/1.73m2 body surface area) and in healthy volunteers. Prasugrel-induced inhibition of platelet aggregation was also comparable in patients with TPAI requiring hemodialysis and in healthy volunteers, although in patients with TPAI the Stakh and AUC of the active metabolite were reduced by 51% and 42%, respectively.

Hepatic failure.

Dose adjustment is not required in patients with mild to moderate hepatic impairment (Child-Pugh grades A and B). Pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation in patients with mild to moderate hepatic impairment and healthy volunteers are comparable. Pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic impairment (Child-Pugh class C) have not been studied. Prasugrel is contraindicated in these patients (see section “Contraindications”).

Children and adolescents under 18 years of age.

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

Indications

– Prasugrel is indicated to prevent thrombotic complications in patients with acute coronary syndrome undergoing percutaneous coronary intervention:

– Patients with unstable angina or myocardial infarction without ST-segment elevation who are undergoing percutaneous coronary intervention;

– Patients with ST-segment elevation myocardial infarction who are undergoing primary or delayed percutaneous coronary intervention.

– Prasugrel is indicated to prevent stent thrombosis in acute coronary syndrome.

Active ingredient

Composition

Each film-coated tablet contains:

The active ingredient: prasugrel hydrochloride 10.98 mg, corresponding to prasugrel (base) 10.00 mg;

Auxiliary substances: Mannitol 67.21 mg, hypromellose 5.285 mg, croscarmellose sodium 11.00 mg, microcrystalline cellulose 78.75 mg, magnesium stearate 1.58 mg; coating: 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 to 0.001 mg.

How to take, the dosage

It is taken orally, regardless of meals. It is not allowed to break the tablet before taking it.

The intake of Prasugrel starts with a single loading dose of 60 mg. Then take a daily maintenance dose of 10 mg.

Patients with ST-elevation coronary angiography within 48 hours of hospitalization should take a loading dose only at the time of percutaneous coronary intervention. Patients taking prasugrel should also take daily ASA (75 to 325 mg daily).

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

Patients weighing less than 60 kg: Prasugrel is started 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 of the active metabolite prasugrel in the blood and an increased risk of bleeding in patients with a body weight 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 Effient® in patients aged 75 years or older is generally not recommended. If after careful individual evaluation by the attending physician of the benefit-risk ratio the treatment is considered necessary, in patients aged 75 years and older, prasugrel is started with a single loading dose of 60 mg and then a daily maintenance dose of 5 mg is prescribed. Patients aged 75 years and older have a greater propensity to bleed and a higher exposure to the active metabolite prasugrel (see sections “Special Precautions”, “Side effects”, “Pharmacodynamics”, “Pharmacokinetics”).

Patients with renal impairment: No dose adjustment is required for patients with renal impairment, including patients with TPA. There is limited experience with prasugrel in patients with renal impairment.

Patients with hepatic impairment: No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh grades A and B). There is limited experience with Prasugrel in patients with mild to moderate hepatic impairment (see section “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: Prasugrel® is not recommended for use in children and adolescents because there is insufficient data on efficacy and safety in this group of patients (see section on Contraindications).

Interaction

Warfarin

Because of the possibility of increased risk of bleeding, concomitant use of warfarin and prasugrel should be used with extreme caution.

NSAIDs

The use of Prasugrel on continuous NSAID therapy has not been studied. Because of the possibility of increased risk of bleeding, the use of prasugrel with ongoing therapy with NSAIDs (including COX-2 inhibitors) should be used with extreme caution.

Drugs metabolized by CYP2B6 isoenzyme

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

Other drug combinations

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 H2 receptor blockers.

Acetylsalicylic acid

Effient® should be taken together with acetylsalicylic acid. Although an increased risk of bleeding is possible with pharmacodynamic interaction with ASA, 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 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 concomitant use of the drug Effient® with heparin.

Special Instructions

Thrombotic thrombocytopenic purpura

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

Surgical interventions

Patients should inform their physicians, including dentists, about the use of prasugrel when planning surgical interventions or prescribing new medications.

If a patient needs a planned surgical intervention and the antiaggregant effect is undesirable, the use of Effient® should be stopped 7 days before the surgical intervention. In patients undergoing CABG there may be an increase in the frequency (3-fold) and severity of bleeding within 7 days after discontinuation of prasugrel.

The benefits and risks of prasugrel should be carefully evaluated in patients in whom coronary anatomy has not been determined and emergency ACS may be performed.

The risk of bleeding

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

For risk factors for bleeding, see Contraindications and Caution.

Hypersensitivity, including angioedema

Hypersensitivity, including angioedema, has been reported in patients taking 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®.

The effect on the ability to drive and operate machinery

There is no established effect of prasugrel on the ability to drive vehicles and operate machinery.

Features

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

Intestation

In oral administration, prasugrel is rapidly absorbed and metabolized. The time of reaching the maximum concentration (Tmax) of the active metabolite in blood serum is reached approximately 0.5 h after administration. AUC of active metabolite increases in direct proportion to the therapeutic dose of the drug.

In healthy volunteers, fatty and high-calorie foods have no effect on the AUC of the active metabolite, but Cmax is decreased by 49%, and Tmax is increased from 0.5 h to 1.5 h. Taking a loading dose of Effient® on an empty stomach may provide a faster onset of action (see section “Dosing regimen”).

Distribution

The binding of the active metabolite 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 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 cysteine conjugation.

In healthy volunteers, patients with stable atherosclerotic process and PCI patients taking Effient® , no genetic variations in the CYP2B6, CYP2C9, CYP2C19, or CYP3A5 isoenzymes were found to affect the pharmacokinetic parameters of prasugrel or suppression of platelet aggregation.

Elimination

Approximately 68% of prasugrel is excreted in the urine and approximately 27% in the feces as inactive metabolites. The t1/2 of the active metabolite is about 7.4 h (interval 2 to 15 h).

Particular patient groups

Patients in the elderly. This study shows that in healthy volunteers aged 20 to 80 years, the pharmacokinetics of prasugrel or inhibition of platelet aggregation is independent of patient age. 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 because of the potential risk of bleeding in this population (see sections “Dosing regimen” and “Caution”). In a study involving patients with stable atherosclerotic disease, the AUC of the active metabolite in a population of patients 75 years and older taking 5 mg prasugrel was approximately half that of patients younger than 65 years taking 10 mg prasugrel, with only patients taking 5 mg having reduced antiaggregant effects of prasugrel.

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

Performance. In healthy volunteers and patients, prasugrel pharmacokinetic parameters do not differ between males and females.

Ethnicity. In clinical pharmacology studies, the AUC of active metabolite (adjusted for body weight) was approximately 19% higher in individuals of Chinese, Japanese and Korean ethnicity compared to individuals of Caucasian race. No differences were found between Chinese, Japanese, and Korean individuals. Exposure was comparable to that of Caucasians in the Negro race and Hispanics. There is no need to adjust the dose according to ethnicity.

Renal insufficiency. No dose adjustment is required for patients with renal impairment, including patients with terminal renal failure (TKF). Pharmacokinetics of prasugrel and its inhibitory effect on platelet aggregation are similar in patients with moderate renal impairment (FFR 30-49 ml/min/1.73 m2 body surface area) and in healthy volunteers. Prasugrel-induced inhibition of platelet aggregation was also comparable in patients with TPN requiring hemodialysis and in healthy volunteers, although in TPN patients Cmax and AUC of the active metabolite were reduced by 51% and 42%, respectively.

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

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

Contraindications

With caution

Risk of bleeding:

Prasugrel should be used with caution in patients with a history of thrombotic thrombocytopenic purpura (see section “Special Precautions”). Prasugrel should be used with special caution and only under medical supervision in patients with a history of angioedema or other hypersensitivity reactions associated with thienopyridines. Prasugrel should be used with caution during pregnancy due to lack of clinical data (see section “Use during pregnancy and breastfeeding”).

Side effects

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

Bleeding not related to ACS

Frequency of complications and bleedinga not related to ACS (% of patients):

a Recorded cases defined by TIMI classification criteria.

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

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

g Life-threatening is a subgroup of major bleeding in the TIMI classification, which includes the types of bleeding shown 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 of ≥3 g/dL but < 5 g/dL.

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

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

*CCS patients who underwent PCI.

** ACS patients who did not undergo PCI.

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

In patients with STEMI who received a loading dose of prasugrel 30 mg on average 4 hours before coronary angiography and 30 mg during subsequent PCI, there was a higher risk of nonACS-related bleeding during the procedure and no additional benefit compared with patients who received a loading dose of 60 mg during PCI.

The incidence of major and minor TIMI-associated non-CABG bleeding in patients at 7 days was as follows:

a Another standard therapy was used if necessary. In clinical trials, all patients also took ASA according to the protocol.

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

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

g EC.

d Bleeding with clinical manifestations accompanied by a decrease in hemoglobin of ≥3 g/dL but < 5 g/dL.

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

In patients over 75 years of age with a body weight less than 60 kg taking prasugrel at a maintenance dose of 5 mg/day for an average of 15 months (maximum 30 months), the incidence of major and minor TIMI non-CABG bleeding in the two weight categories was as follows:

a Supporting dose of 5 mg.

b The maintenance dose is 10 mg; in patients older than 75 years, the maintenance dose is 5 mg.

c A maintenance dose of 75 mg.

The incidence of major and minor bleeding by TIMI classification not associated with ACS in the two age groups was as follows:

a Supporting dose of 5 mg.

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

c Maintaining dose of 75 mg.

Bleeding associated with ACS

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

The number of complications and bleedinga associated with ACS (% 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 reported during clinical trials.

Hemorrhagic adverse reactions

Eye: infrequent (≥0.1% and < 1%) – intraocular hemorrhage.

Vascular disorders: frequently (≥1% and < 10%) – hematoma.

Respiratory system, thorax and mediastinum: frequently (≥1% and < 10%) – nasal bleeding; infrequently (≥0.1% and < 1%) – hemoptysis.

Gastrointestinal disorders: frequently (≥1% and < 10%): gastrointestinal bleeding; infrequently (≥0.1% and < 1%): rectal bleeding, gum bleeding, bloody stool (hematochezia), retroperitoneal bleeding.

Skin and subcutaneous tissue: often (≥1% and < 10%) – ecchymosis.

Renal and urinary tract disorders: often (≥1% < 10%) – hematuria.

General disorders and disorders at the site of administration: frequently (≥1% and < 10%): hematoma at the site of puncture of the vessel, bleeding at the site of puncture.

Injuries, intoxications, and complications of manipulation: frequently (≥1% and < 10%): bruising; infrequently (≥0.1% and < 1%): subcutaneous hematoma, bleeding after procedure.

Nonhemorrhagic adverse reactions

Blood and lymphatic system: frequent (≥1% < 10%) – anemia; infrequent (≥001% and < 0.1%) – thrombocytopenia (platelet count ≤50×109/l).

Skin and subcutaneous tissue: often (≥1% < 10%) – rash.

In clinical trials it has been demonstrated that with standard dosing regimens of prasugrel, patients who have had a previous stroke or TIA have a greater risk of stroke or TIA than patients without a history of these diseases:

Adverse reactions identified by spontaneous message collection

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

Overdose

Symptoms: increased bleeding time and related complications are possible.

Treatment: There is no information about the reversible pharmacological effect of prasugrel; however, if an urgent decrease in bleeding time is required, a transfusion of platelet mass and/or other blood products may be given.