Efient 5mg & 10mg film-coated tablets (Eli Lilly and Company Ltd Daiichi Sankyo UK Ltd)

Medicine Name	Active Ingredients
Medicine Name BENETOR 10mg, 20 mg and 40 mg film-coated tablets	Active Ingredients olmesartan medoxomil
Medicine Name BENETOR PLUS 20mg/12.5mg and 20mg/25mg film-coated tablets	Active Ingredients Hydrochlorothiazide, olmesartan medoxomil
Medicine Name Efient 5mg & 10mg film-coated tablets (Eli Lilly and Company Ltd Daiichi Sankyo UK Ltd)	Active Ingredients prasugrel hydrochloride
Medicine Name Evista	Active Ingredients Raloxifene
Medicine Name Lixiana 15mg, 30mg, 60mg film-coated tablets	Active Ingredients Edoxaban tosilate
Medicine Name Lixiana Film-Coated Tablets	Active Ingredients Edoxaban tosilate

Updated on 12 December 2018 PIL

Reasons for updating

Change to section 2 - interactions with other medicines, food or drink

Updated on 12 December 2018 SmPC

Reasons for updating

Change to section 4.4 - Special warnings and precautions for use
Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 27 May 2016 SmPC

Reasons for updating

New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 27 May 2016 SmPC

Reasons for updating

Change to section 8 - MA number

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Correction to MA numbers

Updated on 23 May 2016 SmPC

Reasons for updating

Change to Section 4.8 – Undesirable effects - how to report a side effect
Change to section 7 - Marketing authorisation holder
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change of MAH from Eli Lily to Daiichi Sankyo Europe

Updated on 17 May 2016 PIL

Reasons for updating

New PIL for new product

Updated on 17 May 2016 PIL

Reasons for updating

Change to date of revision
Change to marketing authorisation holder

Updated on 4 February 2014 SmPC

Reasons for updating

Change to section 4.4 - Special warnings and precautions for use
Change to section 4.8 - Undesirable effects
Change to section 8 - MA number

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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):

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via UK: www.mhra.gov.uk/yellowcard, or Ireland: IMB Phamacovigilance, ~~Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre~~ Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.

8.         MARKETING AUTHORISATION NUMBER(S)

Deleted:

EU/1/08/503/015                   Efient 10mg – 30x1 film-coated tablets

10.          DATE OF REVISION OF THE TEXT

New Date:

18 December 2013

Updated on 2 January 2014 SmPC

Reasons for updating

Change to section 4.2 - Posology and method of administration
Change to section 4.4 - Special warnings and precautions for use
Change to section 4.8 - Undesirable effects
Change to section 5.1 - Pharmacodynamic properties
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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:

Adverse Reaction	Prasugrel Prior to Coronary Angiography^a (N=2037) %	Prasugrel At time of PCI^a (N=1996) %
TIMI Major bleedingb	1.3	0.5
Life-threateningc	0.8	0.2
Fatal	0.1	0.0
Symptomatic ICHd	0.0	0.0
Requiring inotropes	0.3	0.2
Requiring surgical intervention	0.4	0.1
Requiring transfusion (≥4 units)	0.3	0.1
TIMI Minor bleedinge	1.7	0.6

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

Updated on 29 November 2013 SmPC

Reasons for updating

Change to section 2 - Qualitative and quantitative composition
Change to section 4.1 - Therapeutic indications
Change to section 4.2 - Posology and method of administration
Change to section 4.6 - Pregnancy and lactation
Change to section 4.7 - Effects on ability to drive and use machines
Change to Section 4.8 – Undesirable effects - how to report a side effect
Change to section 5.2 - Pharmacokinetic properties
Change to section 9 - Date of renewal of authorisation
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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 population~~Children 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 available~~on safety and efficacy~~.

4.6       Fertility, pregnancy and lactation

Added (bold) deleted (strikethrough):

No clinical study has been conducted in pregnant or breast-feeding ~~lactating~~ women.

Added (subheadings):

Pregnancy

Breast-feeding

Fertility

4.7       Effects on ability to drive and use machines

Deleted (strikethrough):

~~No studies on the effects on ability to drive and use machines have been performed.~~ Prasugrel is expected to have no or negligible influence on the ability to drive and use machines.

4.8           Undesirable effects

Added:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via UK: www.mhra.gov.uk/yellowcard or Ireland: Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, www.imb.ie, imbpharmacovigilance@imb.ie.

5.2       Pharmacokinetic properties

Added (bold) deleted (strikethrough):

Paediatric population:~~Children and adolescents~~:

Pharmacokinetics and pharmacodynamics of prasugrel have not been evaluated in a paediatric population (see section 4.2).

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Added (bold):

Date of first authorisation: 25 February 2009

Date of latest renewal:     13 November 2013

10.          DATE OF REVISION OF THE TEXT

New Date:    Blank

Added:

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

Updated on 26 November 2013 PIL

Reasons for updating

Change to warnings or special precautions for use
Change to side-effects
Change to drug interactions
Change to information about driving or using machinery
Change to date of revision
Change to improve clarity and readability
Addition of information on reporting a side effect.

Updated on 3 July 2013 SmPC

Reasons for updating

Change to section 4.2 - Posology and method of administration
Change to section 4.3 - Contraindications
Change to section 4.8 - Undesirable effects
Change to section 5.1 - Pharmacodynamic properties
Change to section 5.2 - Pharmacokinetic properties
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4. Clinical particulars

4.2 Posology and method of administration

Patients ≥ 75 years old

Deleted:

The evidence for the 5 mg dose is based only on pharmacodynamic/pharmacokinetic analyses and no clinical data currently exist on the safety of this dose in the patients age group ≥ 75 years.

Patients weighing < 60 kg

Deleted:

Efficacy and safety of the 5 mg dose have not been prospectively assessed.

4.3       Contraindications

Added (bold):

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.8          Undesirable effects

Added (bold), deleted (strikethrough):

Patients ≥ 75 years old

~~In the phase 3 clinical trial,~~ Non-CABG‑related TIMI major or minor bleeding rates ~~for patients in two age groups were as follows~~:

Age

Prasugrel 10 mg

Clopidogrel 75 mg

≥75 years (N=1785)*

9.0% (1.0% fatal)

6.9% (0.1% fatal)

<75 years (N=11672)*

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 ACS patients undergoing PCI

**TRILOGY-ACS study in patients not undergoing PCI (see 5.1):

^a 10 mg prasugrel; 5 mg prasugrel if <60 kg

Patients < 60 kg

~~In the phase 3 clinical trial,~~ Non-CABG‑related TIMI major or minor bleeding rates ~~for patients in two age groups were as follows~~:

Weight

Prasugrel 10 mg

Clopidogrel 75 mg

<60 kg (N=664)*

10.1% (0% fatal)

6.5% (0.3% fatal)

≥60 kg (N=12672)*

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 ACS patients undergoing PCI

**TRILOGY-ACS study in patients not undergoing PCI (see 5.1):

^a 10 mg prasugrel; 5 mg prasugrel if ≥75 years of age

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic properties

Added (bold), deleted (strikethrough):

~~Clopidogrel~~Switching data: Following administration of 75 mg clopidogrel once daily for 10 days, 40 healthy subjects were switched to prasugrel 10 mg once daily with or without a loading dose of 60 mg. Similar or higher inhibition of platelet aggregation was observed with prasugrel. Switching directly to prasugrel 60 mg loading dose resulted in the most rapid onset of higher platelet inhibition. Following administration of a 900 mg loading dose of clopidogrel (with ASA), 56 subjects with ACS were treated for 14 days with either prasugrel 10 mg once daily or clopidogrel 150 mg once daily, and then switched to either clopidogrel 150 mg or prasugrel 10 mg for another 14 days. Higher inhibition of platelet aggregation was observed in patients switched to prasugrel 10 mg compared with those treated with clopidogrel 150 mg. ~~No data are available on switching from a clopidogrel loading dose directly to a prasugrel loading dose.~~ In a study of 276 ACS patients managed with PCI, switching from an initial loading dose of 600 mg clopidogrel or placebo administered upon presentation to the hospital prior to coronary angiography to a 60 mg loading dose of prasugrel administered at the time of percutaneous coronary intervention, resulted in a similar increased inhibition of platelet aggregation for the 72 hour duration of the study.

Added:

In a 30 month study (TRILOGY–ACS) in 9326 patients with UA/NSTEMI ACS medically managed without revascularisation (non-licensed indication), prasugrel did not significantly reduce the frequency of the composite endpoint of CV death, MI or stroke compared to clopidogrel. Rates of TIMI major bleeding (including life threatening, fatal and ICH) were similar in prasugrel and clopidogrel treated patients. Patients ≥75 years old or those below 60 kg (N=3022) were randomized to 5 mg prasugrel. As in the < 75 years old and ≥60 kg patients treated with 10 mg prasugrel, there was no difference between 5 mg prasugrel and 75 mg clopidogrel in CV outcomes. Rates of major bleeding were similar in patients treated with 5 mg prasugrel and those treated with 75 mg clopidogrel. Prasugrel 5 mg provided greater antiplatelet effect than clopidogrel 75 mg. Prasugrel should be used with caution in patients ≥ 75 years old and in patients weighing <60 kg (see sections 4.2, 4.4 and 4.8).

5.2       Pharmacokinetic properties

Added (bold):

Special Populations

Elderly: In a study of healthy subjects between the ages of 20 and 80 years, age had no significant effect on pharmacokinetics of prasugrel or its inhibition of platelet aggregation. In the large phase 3 clinical trial, the mean estimated exposure (AUC) of the active metabolite was 19% higher in very elderly patients (≥ 75 years of age) compared to subjects < 75 years of age. Prasugrel should be used with caution in patients ≥ 75 years of age due to the potential risk of bleeding in this population (see sections 4.2 and 4.4). In a study in subjects with stable atherosclerosis, the mean AUC of the active metabolite in patients ≥75 years old taking 5 mg prasugrel was approximately half that in patients < 65 years old taking 10 mg prasugrel, and the antiplatelet effect of 5 mg was reduced but was non-inferior compared to 10 mg.

Added (bold):

Body weight: The mean exposure (AUC) of the active metabolite of prasugrel is approximately 30 to 40% higher in healthy subjects and patients with a body weight of < 60 kg compared to those weighing ≥ 60 kg. Prasugrel should be used with caution in patients with a body weight of < 60 kg due to the potential risk of bleeding in this population (see section 4.4). In a study in subjects with stable atherosclerosis, the mean AUC of the active metabolite in patients <60 kg taking 5 mg prasugrel was 38% lower than in patients ≥60 kg taking 10 mg prasugrel, and the antiplatelet effect of 5 mg was similar to 10 mg.

10.          DATE OF REVISION OF THE TEXT

30 May 2013

Updated on 1 July 2013 PIL

Reasons for updating

Improved electronic presentation

Updated on 7 November 2011 SmPC

Reasons for updating

Change to section 4.4 - Special warnings and precautions for use
Change to section 5.1 - Pharmacodynamic properties
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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

Updated on 31 October 2011 PIL

Reasons for updating

Change to warnings or special precautions for use
Change to further information section
Change to date of revision

Updated on 17 June 2011 PIL

Reasons for updating

Change to warnings or special precautions for use
Change to side-effects
Change to further information section
Change to date of revision

Updated on 6 May 2011 SmPC

Reasons for updating

Change to section 4.4 - Special warnings and precautions for use
Change to section 4.6 - Pregnancy and lactation
Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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)

Added (bold) Deleted (strikethrough):

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

Sub heading updated:

4.6       Fertility, pregnancy and lactation

4.8           Undesirable effects

Added:

a.       Summary of the safety profile

b.       Tabulated summary of adverse reactions

Added (bold):

Table 2 summarises haemorrhagic and non-haemorrhagic adverse reactions in TRITON, or that were spontaneously reported, classified by frequency and system organ class. Frequencies are defined as follows:

Added (bold):

Table 2: Haemorrhagic and Non-haemorrhagic adverse reactions

System Organ Class

Common

Uncommon

Rare

Not Known

Updated on 8 October 2009 SmPC

Reasons for updating

Change to section 4.8 - Undesirable effects
Change to section 5.1 - Pharmacodynamic properties
Change to section 6.5 - Nature and contents of container
Change to section 8 - MA number
Change to section 10 - Date of revision of the text
Introduction of new pack/pack size

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4. Clinical particulars

4.8 Undesirable effects

CABG-related bleeding

Added (bold) Deleted (strikethrough):

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

Added (bold) Deleted (strikethrough):

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

Updated on 30 June 2009 SmPC

Reasons for updating

Change to section 5.1 - Pharmacodynamic properties
Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

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

Updated on 9 June 2009 SmPC

Reasons for updating

Change in co-marketing arrangement

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

First SPC for new product.

10. DATE OF REVISION OF THE TEXT

25 February 2009

Updated on 22 May 2009 PIL

Reasons for updating

Change in co-marketing arrangement

Updated on 5 March 2009 SmPC

Reasons for updating

New SPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 5 March 2009 PIL

Reasons for updating

New PIL for new product

Age	Prasugrel 10 mg	Clopidogrel 75 mg
≥75 years (N=1785)*	9.0% (1.0% fatal)	6.9% (0.1% fatal)
<75 years (N=11672)*	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)

Weight	Prasugrel 10 mg	Clopidogrel 75 mg
<60 kg (N=664)*	10.1% (0% fatal)	6.5% (0.3% fatal)
≥60 kg (N=12672)*	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)

Company Products

Updated on 12 December 2018 PIL

Reasons for updating

Updated on 12 December 2018 SmPC

Reasons for updating

Updated on 27 May 2016 SmPC

Reasons for updating

Updated on 27 May 2016 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 23 May 2016 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 17 May 2016 PIL

Reasons for updating

Updated on 17 May 2016 PIL

Reasons for updating

Updated on 4 February 2014 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 2 January 2014 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 29 November 2013 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 26 November 2013 PIL

Reasons for updating

Updated on 3 July 2013 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 1 July 2013 PIL

Reasons for updating

Updated on 7 November 2011 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 31 October 2011 PIL

Reasons for updating

Updated on 17 June 2011 PIL

Reasons for updating

Updated on 6 May 2011 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 8 October 2009 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 30 June 2009 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 9 June 2009 SmPC

Reasons for updating

Free text change information supplied by the pharmaceutical company

Updated on 22 May 2009 PIL

Reasons for updating

Updated on 5 March 2009 SmPC

Reasons for updating

Updated on 5 March 2009 PIL

Reasons for updating