歐盟終止羥乙基淀粉注射液上市許可

1、The European Medicines Agencys Main navigation PRAC recommends suspending marketing authorisations for infusion solutions containing hydroxyethyl-starch歐洲藥監(jiān)局主導(dǎo)的藥物安全風(fēng)險評估委員會建議含有羥乙基淀粉輸液暫停上市許可。The European Medicines Agencys Pharmacovigilance Risk Assessment Committee (PRAC) has concluded following a rev

2、iew of the available evidence that the benefits of infusion solutions containing hydroxyethyl-starch (HES) no longer outweigh their risks and therefore recommended that the marketing authorisations for these medicines be suspended. 歐洲藥監(jiān)局藥物安全風(fēng)險評估委員會（PRAC）通過對有效證據(jù)評估，得出如下結(jié)論：含有羥乙基淀粉（HES）的注射液風(fēng)險大于利益，因此建議將暫

3、停這些藥品營銷授權(quán)。The review of infusion solutions containing HES was triggered by the German medicines agency, the Federal Institute for Drugs and Medical Devices (BfArM), following three recent studies 1, 2, 3 that compared HES with other products used for volume replacement called crystalloids in critica

4、lly ill patients. The studies showed that patients with severe sepsis treated with HES were at a greater risk of kidney injury requiring dialysis. Two of the studies1,2 also showed that in patients treated with HES there was a greater risk of mortality. The PRAC was therefore requested to assess the

5、 available evidence and how it impacts on the risk-benefit balance of HES infusion solutions in the management of hypovolaemia and hypovolaemic shock. 對羥乙基淀粉（HES）注射液的審查起于德國藥品管理局。美國聯(lián)邦藥品和醫(yī)療器械研究所（BfArM）在危重病人中使用羥乙基淀粉（HES）注射液與使用其他結(jié)晶體注射液做了三個方面最新的對比研究(1,2,3)。研究表明，對羥乙基淀粉（HES）注射液治療嚴(yán)重敗血癥患者時，對需要透析治療的腎損傷者的風(fēng)險更大。

6、兩個研究1，2還表明，使用羥乙基淀粉（HES）注射液的患者中，有更大的死亡風(fēng)險。因此，要求歐洲藥監(jiān)局藥物安全風(fēng)險評估委員會評估現(xiàn)有的證據(jù)，以及它是如何影響在治療低血容量癥和低血容量性休克的HES輸液治療方案上的風(fēng)險和收益平衡。The PRAC assessed data from the scientific literature and the data submitted by the companies, and took advice from a group of external experts. The PRAC was of the opinion that, when com

7、pared with crystalloids, patients treated with HES were at a greater risk of kidney injury requiring dialysis and had a greater risk of mortality. The PRAC also considered that the available data only showed a limited benefit of HES in hypovolaemia, which did not justify its use considering the know

8、n risks. The PRAC therefore concluded that the marketing authorisations for these medicines be suspended.歐洲藥監(jiān)局藥物安全風(fēng)險評估委員會(PRAC)依據(jù)科技文獻(xiàn)和公司所提交的數(shù)據(jù)，結(jié)合征詢外部專家的意見認(rèn)為，與其他結(jié)晶體注射液相比， 羥乙基淀粉（HES）注射液對需要透析治療的腎損傷者的患者風(fēng)險更大，有更大的死亡危險。 PRAC還認(rèn)為，現(xiàn)有的數(shù)據(jù)統(tǒng)計調(diào)查僅顯示出羥乙基淀粉（HES）注射液使有限的低血容量患者受益，這些數(shù)據(jù)沒有證明其使用時考慮到的已知風(fēng)險。 PRAC因此得出結(jié)論，暫停這些藥品的

9、市場營銷授權(quán)。The suspension should remain in place unless the marketing authorisation holder can provide convincing data to identify a group of patients in whom the benefits of the medicines outweigh their risks.暫停上市許證可持有者應(yīng)該留在原地，除非其能提供有說服力的數(shù)據(jù)，能確定大量使用羥乙基淀粉（HES）注射液的患者的利益大于風(fēng)險。The PRAC recommendation will be

10、considered by the Coordination Group for Mutual Recognition and Decentralised Procedures Human (CMDh). PRAC的建議將提交人類用藥品相互承認(rèn)和分散評審程序協(xié)調(diào)組(CMDh)More about the medicineInfusion solutions containing HES are frequently used for volume replacement and belong to the class known as colloids. There are two main

11、types of medicines used for volume replacement: crystalloids and colloids. Colloids contain large molecules such as starch, whereas crystalloids, such as saline (salt) solutions or Ringer acetate, contain smaller molecules. In the European Union (EU), HES-containing solutions for infusion have been

12、approved via national procedures and are available in all Member States under various trade names.藥物簡介含有羥乙基淀粉（HES）的注射液是作為大容量替代輸液被頻繁的使用，被歸類為膠體。目前大容量替代輸液主要有兩種類型：結(jié)晶體液和膠體液。含有大分子量的膠體液如淀粉；而晶體溶液，如鹽水（鹽）溶液或醋酸林格氏液，含有更小的分子量。在歐洲聯(lián)盟，含有羥乙基淀粉的輸注溶液已通過國家程序批準(zhǔn)，可以在所有成員國以各種商標(biāo)使用。More about the procedureThe review of HES s

13、olutions for infusion was initiated on 29 November 2012 at the request of the German medicines agency, under Article 31 of Directive 2001/83/EC.The review has been carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for

14、 human medicines, which has made a set of recommendations. The marketing authorisation holders may request a re-examination within 15 days of being notified of the PRAC recommendation.As these medicines are all authorised nationally, the PRAC recommendation will now be forwarded to the Co-ordination

15、 Group for Mutual Recognition and Decentralised Procedures Human (CMDh), which will adopt a final position. The CMDh is a medicines regulatory body representing the EU Member States.If the CMDh position is agreed by consensus, the agreement will be directly implemented by the Member States where the

16、 medicines are authorised. Should the CMDh position be adopted by majority vote, the CMDh position will be sent to the European Commission, for the adoption of an EU-wide legally binding decision. 有關(guān)程序?qū)u乙基淀粉注射液的審查始于2012年11月29日，由德國藥監(jiān)管理局根據(jù)指令2001/83/EC第31條進(jìn)行。該審查由歐洲藥監(jiān)局藥物安全風(fēng)險評估委員會(PRAC)執(zhí)行，該委員會負(fù)責(zé)對人類的藥品安全

17、問題進(jìn)行評估，目前已提出了一系列建議。并要求市場準(zhǔn)入審查部門根據(jù)PRAC建議在15日內(nèi)重新審查。由于這些藥物使用都是國家授權(quán)，因此PRAC建議將被轉(zhuǎn)發(fā)到歐盟成員國的藥品監(jiān)管機(jī)構(gòu)人類用藥品相互承認(rèn)和分散評審程序協(xié)調(diào)組(CMDh)最終確定。如果人類用藥品相互承認(rèn)和分散評審程序協(xié)調(diào)組一致同意，該協(xié)議將直接由成員國授權(quán)藥物實施。采取投票方式通過后，意見將被發(fā)送到歐盟委員會，在歐盟范圍內(nèi)實施具有法律約束力的決定。1 Perner, A. et al. Hydroxyethyl Starch 130/0.42 versus Ringers acetate in severe sepsis. N Engl J Med 2012; 367(2):124-134.2 Brunkhorst, F.M. et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis