Updated following IB/0028

lactose replaced with lactose monohydrate

Update to align with QRD 10.1

Updated following IB/0028

Update to section 2 lactose to lactose monohydrate

Note: SPC updated to correct errors in formatted version, no other changes have been made.

4.         Clinical particulars

4.4       Special warnings and precautions for use

Moved above Surgery paragraph :

Bleeding Risk Associated with Timing of Loading Dose in NSTEMI

In a clinical trial of NSTEMI patients (the ACCOAST study), where patients were scheduled to undergo coronary angiography within 2 to 48 hours after randomization, a prasugrel loading dose given on average 4 hours prior to coronary angiography increased the risk of major and minor peri-procedural bleeding compared with a prasugrel loading dose at the time of PCI. Therefore, in UA/NSTEMI patients, where coronary angiography is performed within 48 hours after admission, the loading dose should be given at the time of PCI. (see sections 4.2, 4.8 and 5.1).

4.8           Undesirable effects

Reporting of suspected adverse reactions

Added (bold), deleted (strikethrough):

4.         Clinical particulars

4.2           Posology and method of administration

Added (bold):

Posology

Adults

Efient should be initiated with a single 60 mg loading dose and then continued at 10 mg once a day. In UA/NSTEMI patients, where coronary angiography is performed within 48 hours after admission, the loading dose should only be given at the time of PCI (see sections 4.4, 4.8 and 5.1). Patients taking Efient should also take ASA daily (75 mg to 325 mg).

4.4       Special warnings and precautions for use

Added (bold):

Bleeding risk

In the phase 3 clinical trial (TRITON) key exclusion criteria included an increased risk of bleeding; anaemia; thrombocytopaenia; a history of pathological intracranial findings.

Added :

Bleeding Risk Associated with Timing of Loading Dose in NSTEMI

In a clinical trial of NSTEMI patients (the ACCOAST study), where patients were scheduled to undergo coronary angiography within 2 to 48 hours after randomization, a prasugrel loading dose given on average 4 hours prior to coronary angiography increased the risk of major and minor peri-procedural bleeding compared with a prasugrel loading dose at the time of PCI. Therefore, in UA/NSTEMI patients, where coronary angiography is performed within 48 hours after admission, the loading dose should be given at the time of PCI. (see sections 4.2, 4.8 and 5.1).

4.8           Undesirable effects

Added :

Bleeding Risk Associated with Timing of Loading Dose in NSTEMI

In a clinical study of NSTEMI patients (the ACCOAST study), where patients were scheduled to undergo coronary angiography within 2 to 48 hours after randomization, patients given a 30 mg loading dose on average 4 hours prior to coronary angiography followed by a 30 mg loading dose at the time of PCI had an increased risk of non-CABG peri-procedural bleeding and no additional benefit compared to patients receiving a 60 mg loading dose at the time of PCI (see sections 4.2 and 4.4). Non-CABG- related TIMI bleeding rates through 7 days for patients were as follows:

aOther standard therapies were used as appropriate. The clinical study protocol provided for all patients to receive aspirin and a daily maintenance dose of prasugrel.

bAny intracranial haemorrhage or any clinically overt bleeding associated with a fall in haemoglobin ≥5 g/dL.

cLife-threatening is a subset of TIMI Major bleeding and includes the types indented below. Patients may be counted in more than one row.

dICH=intracranial haemorrhage.

eClinically overt bleeding associated with a fall in haemoglobin of ≥3 g/dL but <5 g/dL.

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic properties

In a 30-day study (ACCOAST) in 4033 patients with NSTEMI with elevated troponin who were scheduled for coronary angiography followed by PCI within 2 to 48 hours after randomization, subjects who received prasugrel 30 mg loading dose on average 4 hours prior to coronary angiography followed by a 30 mg loading dose at the time of PCI (n=2037) had an increased risk of non-CABG peri-procedural bleeding and no additional benefit compared to patients receiving a 60 mg loading dose at the time of PCI (n=1996).  Specifically, prasugrel did not significantly reduce the frequency of the composite endpoint of cardiovascular (CV) death, myocardial infarction (MI), stroke, urgent revascularization (UR), or glycoprotein (GP) IIb/IIIa inhibitor bailout through 7 days from randomization in subjects receiving prasugrel prior to coronary angiography compared to patients receiving the full loading dose of prasugrel at the time of PCI, and the rate of the key safety objective for all TIMI major bleeding (CABG and non-CABG events) through 7 days from randomization in all treated subjects was significantly higher in subjects receiving prasugrel prior to coronary angiography versus patients receiving the full loading dose of prasugrel at the time of PCI. Therefore, in UA/NSTEMI patients, where coronary angiography is performed within 48 hours after admission, the loading dose should be given at the time of PCI. (See sections 4.2, 4.4, and 4.8)

10.          DATE OF REVISION OF THE TEXT

New Date:   

18 December 2013

Changes - Minor changes from renewal

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

Added (bold) deleted (strikethrough):

Excipient with known effect: Each tablet contains 2.7 mg lactose.

For a the full list of excipients, see section 6.1.

4.         Clinical particulars

4.1       Therapeutic indications

Added (bold):

Efient, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndrome (i.e. unstable angina, non-ST segment elevation myocardial infarction [UA/NSTEMI] or ST segment elevation myocardial infarction [STEMI]) undergoing primary or delayed percutaneous coronary intervention (PCI).

4.2          Posology and method of administration

Added (bold):

Hepatic impairment

No dose adjustment is necessary in subjects with mild to moderate hepatic impairment (Child-Pugh class A and B) (see section 5.2). There is limited therapeutic experience in patients with mild and moderate hepatic dysfunction (see section 4.4). Efient is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).

Added (bold) deleted (strikethrough):

Paediatric populationChildren and adolescents

The safety and efficacy of Efient is not recommended for use in children below age 18 has not been established. No  due to a lack of data are availableon safety and efficacy.

4.         Clinical particulars

4.2           Posology and method of administration

Patients ≥ 75 years old

Deleted:

4.         Clinical particulars

4.4       Special warnings and precautions for use

Deleted:

Therapeutic experience with prasugrel is limited in Asian patients. Therefore, prasugrel should be used with caution in these patients.

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic properties

Added:

Results of a pharmacodynamic/pharmacogenomic study in 720 Asian ACS PCI patients demonstrated that higher levels of platelet inhibition are achieved with prasugrel compared to clopidogrel, and that prasugrel 60-mg loading dose/10-mg maintenance dose is an appropriate dose regimen in Asian subjects who weigh at least 60 kg and are less than 75 years of age (see section 4.2).

10.          DATE OF REVISION OF THE TEXT

24 October 2011

4.         Clinical particulars

4.4       Special warnings and precautions for use

Added:

Hypersensitivity including angioedema

Hypersensitivity reactions including angioedema have been reported in patients receiving prasugrel, including in patients with a history of hypersensitivity reaction to clopidogrel. Monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is advised (see section 4.8).

Thrombotic Thrombocytopaenic Purpura (TTP)

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TTP has been reported with the use of other thienopyridinesprasugrel. TTP is a serious condition and requires prompt treatment. Efient was not associated with TTP in clinical trials supporting registration.

Sub heading updated:

4.         Clinical particulars

4.8           Undesirable effects

CABG-related bleeding

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For patients who received their last dose of thienopyridine within 4 to 7 days prior to CABG, the frequencies decreased to 11.3% (9 of 80 patients) in the prasugrel group and 3.34% (3 of 90 89 patients) in the clopidogrel group. Beyond 7 days after drug discontinuation, the observed rates of CABG-related bleeding were similar between treatment groups (see section 4.4).

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic properties

Pharmacodynamics

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Prasugrel-mediated inhibition of platelet aggregation exhibits low between-subject (129%) and within-subject (912%) variability with both 5 µM and 20 µM ADP.

6.         PHARMACEUTICAL PARTICULARS

6.5           Nature and contents of container

Added (bold):

Aluminium foil blisters in cartons of 14, 28, 30, 30 (x1), 56, 84, 90 (x1) and 98 tablets.

Not all pack sizes may be marketed.

8.         MARKETING AUTHORISATION NUMBER(S)

Added:

EU/1/08/503/015   Efient 5mg - 30 film-coated tablet

EU/1/08/503/016   Efient 10mg - 30 film-coated tablet

10.          DATE OF REVISION OF THE TEXT

21 September 2009

5.             PHARMACOLOGICAL PROPERTIES

5.1          Pharmacodynamic properties

Added:

Pharmacotherapeutic group: Platelet aggregation inhibitors excluding heparin, ATC code: B01AC22.

10.          DATE OF REVISION OF THE TEXT

18 May 2009

First SPC for new product.

10.          DATE OF REVISION OF THE TEXT

25 February 2009