XII. 参考資料
1. 主な外国での発売状況
プラスグレルは
2009
年2
月にEU
で「第一次又は遅延型経皮的冠動脈形成術（PCI）が適用される、急性冠症 候群（即ち、不安定狭心症［UA
］、非ST
上昇心筋梗塞［NSTEMI
］、ST
上昇心筋梗塞［STEMI
］）患者に おける動脈閉塞性イベントの抑制」の適応で最初に承認を取得した。本剤はこれまでに
EU
加盟国、米国、カナダ、オーストラリア、スイスを含む世界80
ヵ国以上で承認を取得し ている。（2018年
2
月現在）主な外国での効能・効果、用法・用量は以下のとおりである。
出 典 記載内容
米国の添付文書
（EFFIENT- prasugrel hydrochloride tablet, film coated Eli Lilly and Company, 2018年3月）
1 INDICATIONS AND USAGE 1.1 Acute Coronary Syndrome
Effient® is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows:
・ Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
・ Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.
Effient has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel. The difference between treatments was driven predominantly by MI, with no difference on strokes and little difference on CV death [see Clinical Studies (14)].
2 DOSAGE AND ADMINISTRATION
Initiate Effient treatment as a single 60-mg oral loading dose and then continue at 10-mg orally once daily. Patients taking Effient should also take aspirin (75-mg to 325-mg) daily [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)]. Effient may be administered with or without food [see Clinical Pharmacology (12.3) and Clinical Studies (14)].
Timing of Loading Dose
In the clinical trial that established the efficacy and safety of Effient, the loading dose of Effient was not administered until coronary anatomy was established in UA/NSTEMI patients and in STEMI patients presenting more than 12 hours after symptom onset. In STEMI patients presenting within 12 hours of symptom onset, the loading dose of Effient was administered at the time of diagnosis, although most received Effient at the time of PCI [see Clinical Studies (14)]. For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial.
Although it is generally recommended that antiplatelet therapy be administered promptly in the management of ACS because many cardiovascular events occur within hours of initial presentation, in a trial of 4033 NSTEMI patients, no clear benefit was observed when Effient loading dose was administered prior to diagnostic coronary angiography compared to at the time of PCI; however, risk of bleeding was increased with early administration in patients undergoing PCI or early CABG.
Dosing in Low Weight Patients
Compared to patients weighing ≥60 kg, patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10-mg once daily maintenance dose. Consider lowering the maintenance dose to 5-mg in patients
<60 kg. The effectiveness and safety of the 5-mg dose have not been prospectively studied [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Clinical Pharmacology (12.3)].
英国のSPC
（Efient 10mg film-coated tablets, Efient 5mg film-coated tablets, Daiichi Sankyo UK Limited,
2017年3月）
4. Clinical particulars
4.1 Therapeutic indications
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).
For further information please refer to section 5.1.
4.2 Posology and method of administration 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).
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 evaluation 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).
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 (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). Efient is contraindicated in patients with severe hepatic impairment (Child Pugh class C).
Paediatric population
The safety and efficacy of Efient in children below age 18 has not been established. Limited data are available in children with sickle cell anaemia (see section 5.1).
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.
本邦における効能・効果、用法・用量は以下のとおりである。
【効能・効果】
経皮的冠動脈形成術（PCI）が適用される下記の虚血性心疾患
急性冠症候群（不安定狭心症、非
ST
上昇心筋梗塞、ST上昇心筋梗塞）安定狭心症、陳旧性心筋梗塞
〈効能・効果に関連する使用上の注意〉
PCI
が適用予定の虚血性心疾患患者への投与は可能である。冠動脈造影により、保存的治療あるいは冠動脈バイパス術が選択され、
PCI
を適用しない場合には、以後の投与 を控えること。【用法・用量】
通常、成人には、投与開始日にプラスグレルとして
20mg
を1
日1
回経口投与し、その後、維持用量として1
日1
回3.75mg
を経口投与する。〈用法・用量に関連する使用上の注意〉
1.
アスピリン（81～100mg/日、なお初回負荷投与では324mg
まで）と併用すること。2.
ステント留置患者への本剤投与時には該当医療機器の添付文書を必ず参照すること。3. PCI
施行前に本剤3.75mg
を5
日間程度投与されている場合、初回負荷投与（投与開始日に20mg
を投与すること）は必須ではない。（本剤による血小板凝集抑制作用は
5
日間で定常状態に達することが想定される。）4.
空腹時の投与は避けることが望ましい（初回負荷投与を除く）。（「薬物動態」、「臨床成績」の項参照）5. OD
錠は口腔内で速やかに崩壊するが、口腔粘膜からの吸収により効果発現を期待する薬剤ではないため、崩壊後は唾液又は水で飲み込むこと。