Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 6

HOS-120778 · Präparat HOS-095209

Effects of Efient on other medicinal products Digoxin: Prasugrel has no clinically significant effect on the pharmacokinetics of digoxin.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): digoxin (HOS-086172)

Wechselwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 6

HOS-120779 · Präparat HOS-095209

Medicinal products metabolised by CYP2C9: Prasugrel did not inhibit CYP2C9, as it did not affect the pharmacokinetics of S-warfarin. Because of the potential for increased risk of bleeding, warfarin and Efient should be co-administered with caution (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): warfarin (HOS-085950)

Wechselwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 6

HOS-120780 · Präparat HOS-095209

Medicinal products metabolised by CYP2B6: Prasugrel is a weak inhibitor of CYP2B6. In healthy subjects, prasugrel decreased exposure to hydroxybupropion, a CYP2B6-mediated metabolite of bupropion, by 23%. This effect is likely to be of clinical concern only when prasugrel is co-administered with medicinal products for which CYP2B6 is the only metabolic pathway and have a narrow therapeutic window (e.g. cyclophosphamide, efavirenz).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): bupropion (HOS-086329) cyclophosphamide (HOS-084539) efavirenz (HOS-087947)

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 7

HOS-120781 · Präparat HOS-095209

Summary of the safety profile Safety in patients with acute coronary syndrome undergoing PCI was evaluated in one clopidogrel- controlled study (TRITON) in which 6741 patients were treated with prasugrel (60 mg loading dose and 10 mg once daily maintenance dose) for a median of 14.5 months (5802 patients were treated for over 6 months, 4136 patients were treated for more than 1 year). The rate of study drug discontinuation due to adverse events was 7.2% for prasugrel and 6.3% for clopidogrel. Of these, bleeding was the most common adverse reaction for both drugs leading to study drug discontinuation (2.5% for prasugrel and 1.4% for clopidogrel).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 7

HOS-120782 · Präparat HOS-095209

Bleeding Non-Coronary Artery Bypass Graft (CABG) related bleeding In TRITON, the frequency of patients experiencing a non-CABG related bleeding event is shown in Table 1. The incidence of Non-CABG-related TIMI major bleeding, including life-threatening and fatal, as well as TIMI minor bleeding, was statistically significantly higher in subjects treated with prasugrel compared to clopidogrel in the UA/NSTEMI and All ACS populations. No significant difference was seen in the STEMI population. The most common site of spontaneous bleeding was the gastrointestinal tract (1.7% rate with prasugrel and 1.3% rate with clopidogrel); the most frequent site of provoked bleeding was the arterial puncture site (1.3% rate with prasugrel and 1.2% with clopidogrel).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 7–8

HOS-120783 · Präparat HOS-095209

7 Table 1: Incidence of Non-CABG related bleedinga (% Patients) Event All ACS UA/NSTEMI STEMI Prasugrelb Clopidogrelb Prasugrelb Clopidogrelb Prasugrelb Clopidogrelb +ASA +ASA +ASA +ASA +ASA +ASA (N=6741) (N=6716) (N=5001) (N=4980) (N=1740) (N=1736) TIMI major 2.2 1.7 2.2 1.6 2.2 2.0 bleedingc Life-threateningd 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 Symptomatic 0.3 0.3 0.3 0.3 0.2 0.2 ICHe Requiring 0.3 0.1 0.3 0.1 0.3 0.2 inotropes Requiring 0.3 0.3 0.3 0.3 0.1 0.2 surgical intervention Requiring 0.7 0.5 0.6 0.3 0.8 0.8 transfusion (≥ 4 units) TIMI minor 2.4 1.9 2.3 1.6 2.7 2.6 bleeding f a Centrally adjudicated events defined by the Thrombolysis in Myocardial Infarction (TIMI) Study Group criteria. b Other standard therapies were used as appropriate. c Any intracranial haemorrhage or any clinically overt bleeding associated with a fall in haemoglobin ≥ 5 g/dL. d Life-threatening bleeding is a subset of TIMI major bleeding and includes the types indented below. Patients may be counted in more than one row. e ICH=intracranial haemorrhage. f Clinically overt bleeding associated with a fall in haemoglobin of ≥ 3 g/dL but < 5 g/dL.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-120784 · Präparat HOS-095209

Patients ≥ 75 years old Non-CABG-related TIMI major or minor bleeding rates:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-120785 · Präparat HOS-095209

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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-120786 · Präparat HOS-095209

Patients < 60 kg Non-CABG-related TIMI major or minor bleeding rates:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-120787 · Präparat HOS-095209

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 < 60 kg (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

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-120788 · Präparat HOS-095209

Patients ≥ 60 kg and age < 75 years In patients ≥ 60 kg and age < 75 years, non-CABG-related TIMI major or minor bleeding rates were 3.6% for prasugrel and 2.8% for clopidogrel; rates for fatal bleeding were 0.2% for prasugrel and 0.1% for clopidogrel.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8–9

HOS-120789 · Präparat HOS-095209

8 CABG-related bleeding In the phase 3 clinical trial, 437 patients underwent CABG during the course of the study. Of those patients, the rate of CABG-related TIMI major or minor bleeding was 14.1% for the prasugrel group and 4.5% in the clopidogrel group. The higher risk for bleeding events in subjects treated with prasugrel persisted up to 7 days from the most recent dose of study drug. For patients who received their thienopyridine within 3 days prior to CABG, the frequencies of TIMI major or minor bleeding were 26.7% (12 of 45 patients) in the prasugrel group, compared with 5.0% (3 of 60 patients) in the clopidogrel group. 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 3.4% (3 of 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).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-120790 · Präparat HOS-095209

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:

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-120791 · Präparat HOS-095209

Prasugrel Prior to Prasugrel At Adverse Reaction Coronary time of PCIa Angiographya (N=2037) (N=1996) % %

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-120792 · Präparat HOS-095209

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 a Other 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. c Life-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. e Clinically overt bleeding associated with a fall in haemoglobin of ≥ 3 g/dL but < 5 g/dL.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9–10

HOS-120793 · Präparat HOS-095209

9 Tabulated summary of adverse reactions 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: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 10

HOS-120794 · Präparat HOS-095209

Table 2: Haemorrhagic and Non-haemorrhagic adverse reactions System Organ Common Uncommon Rare Not Known Class Blood and Anaemia Thrombocytopaenia Thrombotic Lymphatic System thrombocytopaenic disorders purpura (TTP) -see section 4.4 Immune system Hypersensitivity disorders including angioedema Eye disorders Eye haemorrhage Vascular Disorders Haematoma Respiratory, Epistaxis Haemoptysis thoracic and mediastinal disorders Gastrointestinal Gastrointestinal Retroperitoneal disorders haemorrhage haemorrhage Rectal haemorrhage Haematochezia Gingival bleeding Skin and Rash subcutaneous tissue Ecchymosis disorders Renal and urinary Haematuria disorders General disorders Vessel puncture site and administration haematoma site conditions Puncture site haemorrhage Injury, poisoning Contusion Post-procedural Subcutaneous and procedural haemorrhage haematoma complications

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 10

HOS-120795 · Präparat HOS-095209

In patients with or without a history of TIA or stroke, the incidence of stroke in the phase 3 clinical trial was as follows (see section 4.4):

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 10

HOS-120796 · Präparat HOS-095209

History of TIA or stroke Prasugrel Clopidogrel Yes (N=518) 6.5% (2.3% ICH*) 1.2% (0% ICH*) No (N=13090) 0.9% (0.2% ICH*) 1.0% (0.3% ICH*) * ICH=intracranial haemorrhage.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Efient

Efient 10 mg film-coated tablets. Efient 5 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 10

HOS-120797 · Präparat HOS-095209

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 the national reporting system listed in Appendix V.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.