Efient* 5 mg film-coated tablets. Efient 10mg film-coated t(六)
rises 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).
Table 2: Haemorrhagic and Non-haemorrhagic adverse reactions
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):
* ICH=intracranial haemorrhage.
4.9 Overdose
Overdose of Efient may lead to prolonged bleeding time and subsequent bleeding complications. No data are available on the reversal of the pharmacological effect of prasugrel; however, if prompt correction of prolonged bleeding time is required, platelet transfusion and/or other blood products may be considered.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Platelet aggregation inhibitors excluding heparin. ATC code: B01AC22.
Pharmacodynamics
Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function can result in the reduction of the rate of cardiovascular events such as death, myocardial infarction, or stroke.
Following a 60 mg loading dose of prasugrel, inhibition of ADP-induced platelet aggregation occurs at 15 minutes with 5 μM ADP and 30 minutes with 20 μM ADP. The maximum inhibition by prasugrel of ADP-induced platelet aggregation is 83% with 5 μM ADP and 79% with 20 μM ADP, in both cases with 89% of healthy subjects and patients with stable atherosclerosis achieving at least 50% inhibition of platelet aggregation by 1 hour. Prasugrel-mediated inhibition of platelet aggregation exhibits low between-subject (9%) and within-subject (12%) variability with both 5 μM and 20 μM ADP. Mean steady-state inhibition of platelet aggregation was 74% and 69% respectively for 5 μM ADP and 20 μM ADP, and was achieved following 3 to 5 days of administration of the 10 mg prasugrel maintenance dose preceded by a 60 mg loading dose. More than 98% of subjects had 20% inhibition of platelet aggregation during maintenance dosing.
Platelet aggregation gradually returned to baseline values after treatment in 7 to 9 days after administration of a single 60 mg loading dose of prasugrel, and in 5 days following discontinuation of maintenance dosing at steady-state.
Clopidogrel: 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 prasugre |
