Medicinal Products

EFIENT 10 mg

Generic drug of the therapeutic class: Haemostasis and blood
Active ingredients: Prasugrel
laboratory: Eli Lilly Nederland

Coated tablet
Box of 90 Blister packs of 1
All forms

Indication

Efient, in combination with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (ie, unstable angina, myocardial infarction without segmental elevation). ST [AI / NSTEMI] or ST segment elevation myocardial infarction [STEMI]) treated with primary or delayed percutaneous coronary intervention (PCI).

For more information, see section 5.1 Pharmacodynamic properties .

Dosage EFIENT 10 mg Film-coated tablet Box of 90 Blister packs of 1

Dosage

adults

Efient should be initiated at a single 60 mg loading dose and then continued with a 10 mg once daily dose. Efient patients should also take acetylsalicylic acid daily (75 mg to 325 mg dose).

In patients with acute coronary syndrome (ACS) treated with PCI, premature discontinuation of any platelet antiaggregant, including Efient, may result in an increased risk of thrombosis, myocardial infarction, or death due to underlying disease of the patient. Treatment of up to 12 months is recommended unless an Efient discontinuation is clinically indicated (see sections Warnings and Precautions and Pharmacodynamic Properties ).

Patients ≥75 years

Use of Efient in patients 75 years is generally not recommended. If, after a careful evaluation of the individual benefit / risk ratio by the prescribing physician (see Warnings and Precautions section ), treatment is considered necessary in patients 75 years, then a reduced maintenance dose of 5 mg should be prescribed after a loading dose of 60 mg. Patients 75 years of age have an increased susceptibility to bleeding and increased exposure to the active metabolite of prasugrel (see Warnings and Precautions, Adverse Reactions, Pharmacodynamic Properties and Pharmacokinetic Properties sections).

Patients weighing <60 kg

Efient should be administered as a single 60 mg loading dose and continued at a dose of 5 mg once daily. The maintenance dose of 10 mg is not recommended. This is due to an increase in exposure to the active metabolite of prasugrel and an increased risk of bleeding in patients <60 kg when given a daily dose of 10 mg compared to patients 60 kg (see sections Mises caution and precautions for use, adverse reactions and pharmacokinetic properties ).

Renal failure

No dose adjustment is necessary in patients with renal impairment, including patients with end-stage renal disease (see section 5.2 ). Therapeutic experience is limited in patients with renal impairment (see Warnings and Precautions section ).

Hepatic insufficiency

No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B) (see section 5.2 ). Therapeutic experience is limited in patients with mild to moderate abnormalities of liver function (see Warnings and Precautions ). Efient is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).

Pediatric population

The safety and effectiveness of Efient in children under 18 years have not been established. No data available.

Administration mode

Orally. Efient can be administered during or without meals. Administration of the fasting 60 mg dose of prasugrel may result in a faster onset of action (see section 5.2 ). Do not crush or cut the tablet.

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under Composition .
Pathological bleeding proved.

History of stroke or transient ischemic attack (TIA).
Severe hepatic insufficiency (Child-Pugh class C).

Adverse effects Efient

Summary of the security profile

The safety of prasugrel in patients with acute coronary syndrome treated with PCI was evaluated in a controlled study versus clopidogrel (TRITON) in which 6, 741 patients were treated with prasugrel (60 mg loading dose and 10 mg once daily) for a median duration of 14.5 months (5 802 patients were treated for more than 6 months, 4 136 patients were treated for more than one year). The discontinuation rate of study drug due to adverse events was 7.2% for prasugrel and 6.3% for clopidogrel. Among these events, bleeding was the most common adverse event leading to discontinuation of treatment with both study drugs (2.5% for prasugrel and 1.4% for clopidogrel).

Bleeding

Bleeding unrelated to coronary bypass (PC)

In the TRITON trial, the frequency of patients with unrelated hemorrhagic events is shown in Table 1. The incidence of unrelated major bleeds (TIMI criteria), including life-threatening bleeding or fatal, as well as the incidence of minor bleeds (TIMI criteria) were statistically significantly higher in prasugrel-treated subjects compared to clopidogrel in the AI ​​/ NSTEMI population and the overall SCA population. No significant difference was observed in the STEMI population. The most common spontaneous bleeding site was the gastrointestinal tract (1.7% with prasugrel and 1.3% with clopidogrel); the most frequent site of bleeding was the site of arterial puncture (1.3% with prasugrel and 1.2% with clopidogrel).

Table 1: Incidence of bleeding unrelated to a PC at (% of patients)

Event

All SCA

UA / NSTEMI

STEMI

Prasugrel b

+ ASA

(N = 6, 741)

Clopidogrel b

+ ASA

(N = 6, 716)

Prasugrel b

+ ASA

(N = 5, 001)

Clopidogrel b

+ ASA

(N = 4, 980)

Prasugrel b

+ ASA

(N = 1740)

Clopidogrel b

+ ASA

(N = 1736)

Major bleeding according to criteria

TIMI c

2.2

1.7

2.2

1.6

2.2

2.0

Committing the prognosis

vital d

1.3

0.8

1.3

0.8

1.2

1.0

Fatal

0.3

0.1

0.3

0.1

0.4

0.1

HIC symptomati

-that

0.3

0.3

0.3

0.3

0.2

0.2

requiring

of the

inotropic

0.3

0.1

0.3

0.1

0.3

0.2

requiring

a

interventio

surgical

0.3

0.3

0.3

0.3

0.1

0.2

Requiring a

transfusion

(≥ 4 units)

0.7

0.5

0.6

0.3

0.8

0.8

Minor bleeding according to TIMI criteria f

2.4

1.9

2.3

1.6

2.7

2.6

a Centrally evaluated events defined by the TIMI study group criteria (Thrombolysis in Myocardial Infarction)

b If necessary, other usual treatments have been used.

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

d The life-threatening bleeding of patients is a subset of major bleeding according to the TIMI criteria and includes the types indented in the lines below. Patients can be counted in multiple lines.

HIC = intracranial hemorrhage.

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

Patients ≥75 years

Major or minor bleeding rate according to TIMI criteria, unrelated to a PC:

Age

Prasugrel 10 mg

Clopidogrel 75 mg

75 years (N = 1, 785) *

9.0% (1.0% fatal)

6.9% (0.1% fatal)

<75 years (N = 11, 672) *

3.8% (0.2% fatal)

2.9% (0.1% fatal)

<75 years (N = 7180) **

2.0% (0.1% fatal) a

1.3% (0.1% fatal)

Prasugrel 5 mg

Clopidogrel 75 mg

75 years (N = 2060) **

2.6% (0.3% fatal)

3.0% (0.5% fatal)

* TRITON study in patients with SCA supported by ICP

** TRILOGY-ACS study in patients not supported by ICP (see section on Pharmacodynamic properties ):

prasugrel 10 mg; prasugrel 5 mg if patients <60 kg

Patients <60 kg

Major or minor bleeding rate according to TIMI criteria, unrelated to a PC:

Weight

Prasugrel 10 mg

Clopidogrel 75 mg

<60 kg (N = 664) *

10.1% (0% fatal)

6.5% (0.3% fatal)

60 kg (N = 12, 672) *

4.2% (0.3% fatal)

3.3% (0.1% fatal)

60 kg (N = 7845) **

2.2% (0.2% fatal) a

1.6% (0.2% fatal)

Prasugrel 5 mg

Clopidogrel 75 mg

<60kg (N = 1391) **

1.4% (0.1% fatal)

2.2% (0.3% fatal)

* TRITON study in patients with SCA supported by ICP

** TRILOGY-ACS study in patients not supported by ICP (see section on Pharmacodynamic properties ):

prasugrel 10 mg; prasugrel 5 mg if patients ≥ / 7 5 years

Patients ≥ 60 kg and <75 years old

In patients 60 kg and < 75 years, the major or minor bleeding rates according to TIMI criteria not related to PC were 3.6% for prasugrel and 2.8% for clopidogrel; fatal bleeding rates were 0.2% for prasugrel and 0.1% for clopidogrel.

Bleeding in connection with a PC

In the phase III trial, 437 patients underwent a PC during the study. Among these patients, the major or minor bleeding rates according to TIMI criteria, in relation to a PC, were 14.1% in the prasugrel group and 4.5% in the clopidogrel group. The increased risk of bleeding events in subjects treated with prasugrel persisted for up to 7 days after the last dose of study drug. For patients who received their thienopyridine in the 3 days prior to the PC, the major or minor bleeds according to the TIMI criteria were 26.7% (12 of 45 patients) in the prasugrel group, compared to 5.0% ( 3 of 60 patients) in the clopidogrel group. For patients who received their last dose of thienopyridine in the 4 to 7 days prior to the PC, the frequencies were reduced to 11.3% (9 of 80 patients) in the prasugrel group and to 3.4% (3 of 89 patients). patients) in the clopidogrel group. Beyond 7 days after stopping the drug, the observed rates of bleeding in relation to a PC were similar between the treatment groups (see Warnings and Precautions section ).

Summary table of adverse effects

Table 2 summarizes the hemorrhagic and non-bleeding adverse effects from the TRITON study, or spontaneous notification, classified by frequency and organ system classes. Frequencies are defined as follows:

Very common ( 1/10) frequent ( 1/100 to <1/10); uncommon ( 1/1000 to <1/100);

rare ( 1/10 000 to <1/1000); very rare (<1 / 10, 000); unknown (can not be estimated from the available data).

Table 2 : Hemorrhagic and non-hemorrhagic adverse effects

Class of organ systems

frequent

Uncommon

few

unknown

unrest

hematologic and lymphatic system

Anemia

Thrombocytopenia

purpura

thrombocytopenic

thrombotic (PTT) - see section Warnings and precautions for use

Immune system disorders

hypersensitivity

including

angioedema

Eye disorders

Ocular haemorrhage

Vascular disorders

Hematoma

Respiratory, thoracic and mediastinal disorders

Epistaxis

hemoptysis

Gastrointestinal disorders

Gastrointestinal bleeding

Hemorrhage

retroperitoneal

Hemorrhage

rectal

haematochezia

gingival

Skin and subcutaneous tissue disorders

Rash Bruise

Renal and urinary disorders

hematuria

General Disorders and Administration Site

Hematoma at the site of vascular puncture Hemorrhage at the site of puncture

injury,

poisoning and complications secondary to a procedure

Contusion

Post procedural haemorrhage

Subcutaneous hematoma

In patients with or without a history of TIA or stroke, the incidence of stroke in the Phase III trial was as follows (see Warnings and Precautions ):

History of TIA or stroke

prasugrel

clopidogrel

Yes (N = 518)

6.5% (2.3% HIC *)

1.2% (0% HIC *)

No (N = 13, 090)

0.9% (0.2% HIC *)

1.0% (0.3% HIC *)

* HIC = intracranial hemorrhage.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system

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