Efient* 5 mg film-coated tablets.

Efient 10 mg film-coated tablets.

Each tablet contains 5 mg prasugrel (as hydrochloride).

Excipient: Each tablet contains 2.7 mg lactose.

Each tablet contains 10 mg prasugrel (as hydrochloride).

Excipient: Each tablet contains 2.1 mg lactose.

For a full list of excipients, see section 6.1.

Film-coated tablet (tablet).

Yellow and double-arrow-shaped tablets, debossed with “5 MG” on one side and “4760” on the other.

Film-coated tablet (tablet).

Beige and double-arrow-shaped tablets, debossed with “10 MG”on one side and “4759” on the other.

Efient, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in 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).

For further information please refer to section 5.1.

Posology

Adults

Efient should be initiated with a single 60 mg loading dose and then continued at 10 mg once a day. Patients taking Efient should also take ASA daily (75 mg to 325 mg).

In patients with acute coronary syndrome (ACS) who are managed with PCI, premature discontinuation of any antiplatelet agent, including Efient, could result in an increased risk of thrombosis, myocardial infarction or death due to the patient's underlying disease. A treatment of up to 12 months is recommended, unless the discontinuation of Efient is clinically indicated (see sections 4.4 and 5.1).

Patients 75 years old

The use of Efient in patients 75 years of age is generally not recommended. If, after a careful individual benefit/risk eva luation by the prescribing physician (see section 4.4), treatment is deemed necessary in the patients age group 75 years, then following a 60 mg loading dose a reduced maintenance dose of 5 mg should be prescribed. Patients 75 years of age have greater sensitivity to bleeding and higher exposure to the active metabolite of prasugrel (see sections 4.4, 4.8, 5.1 and 5.2). 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

Efient should be given as a single 60 mg loading dose and then continued at a 5 mg once-daily dose. The 10 mg maintenance dose 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 with body weight <60 kg when given a 10 mg once-daily dose, compared with patients 60 kg. Efficacy and safety of the 5 mg dose have not been prospectively assessed (see sections 4.4, 4.8 and 5.2).

Renal impairment

No dose adjustment is necessary for patients with renal impairment, including patients with end-stage renal disease (see section 5.2). There is limited therapeutic experience in patients with renal impairment (see section 4.4).

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).

Children and adolescents

Efient is not recommended for use in children below age 18 due to a lack of data on safety and efficacy.

Method of administration

For oral use. Efient may be administered with or without food. Administration of the 60 mg prasugrel loading dose in the fasted state may provide most rapid onset of action (see section 5.2). Do not crush or break the tablet.

Hypersensitivity to the active substance or to any of the excipients.

Active pathological bleeding.

History of stroke or transient ischaemic attack (TIA).

Severe hepatic impairment (Child-Pugh class C).

Bleeding risk

In the phase 3 clinical trial, key exclusion criteria included an increased risk of bleeding; anaemia; thrombocytopaenia; a history of pathological intracranial findings. Patients with acute coronary syndromes undergoing PCI treated with Efient and ASA showed an increased risk of major and minor bleeding according to the TIMI classification system. Therefore, the use of Efient in patients at increased risk of bleeding should only be considered when the benefits in terms of prevention of ischaemic events are deemed to outweigh the risk of serious bleedings. This concern applies especially to patients:

•75 years of age (see below).

• with a propensity to bleed (e.g., due to recent trauma, recent surgery, recent or recurrent gastrointestinal bleeding, or active peptic ulcer disease).

• with body weight <60 kg (see sections 4.2 and 4.8). In these patients the 10 mg maintenance dose is not recommended. A 5 mg maintenance dose should be used.

• with concomitant administration of medicinal products that may increase the risk of bleeding, including oral anticoagulants, clopidogrel, non-steroidal anti-inflammatory drugs (NSAIDs), and fibrinolytics.

For patients with active bleeding for whom reversal of the pharmacological effects of Efient is required, platelet transfusion may be appropriate.

The use of Efient in patients 75 years of age is generally not recommended, and should only be undertaken with caution after a careful individual benefit/risk eva luation by the prescribing physician indicates that benefits in terms of prevention of ischaemic events outweigh the risk of serious bleedings. In the phase 3 clinical trial these patients were at greater risk of bleeding, including fatal bleeding, compared to patients <75 years of age. If prescribed, a lower maintenance dose of 5 mg should be used; the 10 mg maintenance dose is not recommended (see sections 4.2 and 4.8).

Therapeutic experience with prasugrel is limited in patients with renal impairment (including ESRD) and in patients with moderate hepatic impairment. These patients may have an increased bleeding risk. Therefore, prasugrel should be used with caution in these patients.

Patients should be told that it might take longer than usual to stop bleeding when they take prasugrel (in combination with ASA), and that they should report any unusual bleeding (site or duration) to their physician.

Surgery

Patients should be advised to inform physicians and dentists that they are taking prasugrel before any surgery is scheduled, and before any new medicinal product is taken. If a patient is to undergo elective surgery, and an antiplatelet effect is not desired, Efient should be discontinued at least 7 days prior to surgery. Increased frequency (3-fold) and severity of bleeding may occur in patients undergoing CABG surgery within 7 days of discontinuation of prasugrel (see section 4.8). The benefits and risks of prasugrel should be carefully considered in patients in whom the coronary anatomy has not been defined, and urgent CABG is a possibility.

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 Thrombocytopenic Purpura (TTP)

TTP has been reported with the use of prasugrel. TTP is a serious condition and requires prompt treatment.

Lactose

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Efient.

Warfarin: Concomitant administration of Efient with coumarin derivatives other than warfarin has not been studied. Because of the potential for increased risk of bleeding, warfarin (or other coumarin derivatives) and prasugrel should be co-administered with caution (see section 4.4).

Non-steroidal anti-inflammatory drugs (NSAIDs): Concomitant administration with chronic NSAIDs has not been studied. Because of the potential for increased risk of bleeding, chronic NSAIDs (includi