AktuellerZulassungsstatusvon HAES-Produkten

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Edmund Hofer
vor 8 Jahren
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1 AktuellerZulassungsstatusvon HAES-Produkten Dr. Frank Dalbeck Fresenius Kabi Deutschland Frankfurt, den

2 As the CMDh position has been adopted by majority vote, it will now be sent to the European Commission, which will take a final legally binding decision that will be valid throughout the European Union (EU).

3 CMDhStatement: More about the procedures (I) Review of HES solutions initiated on 29 November 2012 (requested by the German medicines agency, under Article 31 of Directive 2001/83/EC) Pharmacovigilance Risk Assessment Committee (PRAC), concluded on 13 June 2013: 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 Marketing authorisation holders requested a re-examination. Some Member States decided to suspend or limit the marketing or use of HES products in their territories. Consequently, on 27 June 2013, the UK triggered an EU review of HES solutions under Article 107i of Directive 2001/83/EC. This review procedure ran in parallel with the re-examination of the PRAC s June 2013 recommendation Both procedures were finalised on 10 October 2013.

recommended that the marketing authorisations for these medicines be suspended Marketing authorisation holders requested a re-examination.

4 CMDhStatement: More about the procedures (II) For the re-examination procedure the PRAC confirmed its previous position. However, new evidence was considered in the parallel Article 107i procedureand this was the basis for the PRAC sfinal recommendation on the use of HES solutions. PRAC recommendations were forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures Human (CMDh), CMDh adopted a final position. As the CMDh position was adopted by majority vote, the CMDh position wassent to the European Commission, for the adoption of an EU-wide legally binding decision.

5 Response of Stakeholders in the Article 107i Referral Procedure Benefit-risk positive in defined patient populations (> 80% of the stakeholders) The most important notions were: Results of the CRISTAL study are significantly different from the results of the previous trials. The new evaluated trials suggesting favourable benefit-risk balance for treatment of critically ill patients. The negative results of studies in patients with severe sepsis may not be extrapolated to other patients groups and indications. While the clinical practice is in accordance with the guidelines, the trials with negative results do deviate from the recommendations.

The new evaluated trials suggesting favourable benefit-risk balance for treatment of critically ill patients.

6 Meybohm P, Van Aken H, De Gasperi A, De Hert S, Della Rocca G, Girbes AR, Gombotz H, Guidet B, Hasibeder W, Hollmann M, Ince C, Jacob M, Kranke P, Kozek-Langenecker S, Loer SA, Martin CD, Siegemund M, Wunder C, Zacharowski K. Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethylstarch in critically ill patients - a multidisciplinary statement. Crit Care 2013, 17(4):R166.

7 CMDh Statement: Information for healthcare professionals

8 CMDh Statement: Information for healthcare professionals

9 CMDh Statement: Information for healthcare professionals

10 CMDh Statement: Information for healthcare professionals A

11 CMDh Statement: Information for healthcare professionals A

12 CMDh Statement: Information for healthcare professionals A

13 Zusammenfassung Studie VISEP (IIT) Publikation Patientenanzahl Indikation Patienten mit Sepsis Studienmedikation Konzipiert zum Nachweis von Ergebnisse 10% HES 200/0.5 (Hemohaes ) vs. Ringer-Lactat Wirksamkeit & Sicherheit (-) mehr Nierenversagen CRYSTMAS (Firmeninitiert) Patienten mit Sepsis 6% HES 130/0.4 (Voluven ) vs. 0,9% NaCl Wirksamkeit (+) schnellere hämodynamische Stabilisierung weniger Volumen zur hämodynamischen Stabilisierung notwendig kein Unterschied bzgl. Nierenversagen 6S (IIT) Patienten mit Sepsis 6% HES 130/0.42 (Tetraspan ) vs. Sterofundin-ISO Wirksamkeit & Sicherheit (-) erhöhte Letalität mehr Nierenversagen

14 Zusammenfassung Studie CHEST (IIT) BaSES (IIT) Publikation Patientenanzahl Indikation ITS- Patienten, davon 2000 mit Sepsis 2013 erwartet 250 Sepsis Studienmedikation Konzipiert zum Nachweis von Ergebnisse 6% HES 130/0.4 (Voluven ) vs. 0,9% NaCl 6% HES 130/0.4 (Voluven ) vs. Ringer-Lactat Wirksamkeit (+/-), Sicherheit (+) vergleichbare Letalität weniger renal risk und injury gem. RIFLE-Kriterien kein Unterschied bzgl. Nierenversagen gem. RIFLE-Kriterien mehr RRT, aber vergleichbare Dauer Wirksamkeit (+) kürzerer ITS- und KH-Aufenthalt kein Unterschied bzgl. Nierenversagen vergleichbare Letalität

0,9% NaCl 6% HES 130/0.4 (Voluven ) vs. Ringer-Lactat Wirksamkeit (+/-), Sicherheit (+) vergleichbare Letalität weniger renal risk und injury gem.

15 Zusammenfassung Studie CRISTAL (IIT) RaFTinG (IIT) Publikation Patientenanzahl Indikation ITS Kolloide & Kristalloide 2013 erwartet ITS Kolloide & Kristalloide Studienmedikation Konzipiert zum Nachweis von Ergebnisse Wirksamkeit & Sicherheit (+) vergleichbare 28-Tages Letalität, geringere 90-Tages Letalität Trend geringere ITS-Letalität, geringere KH-Letalität kein Unterschied bzgl. Nierenversagen (Tag 7: Trend für weniger RRT) Sicherheit (+) kein Unterschied bzgl. Nierenversagen

000 ITS Kolloide & Kristalloide Studienmedikation Konzipiert zum Nachweis von Ergebnisse Wirksamkeit & Sicherheit (+)

16 Entwicklung von HES-Lösungen Molekulargewicht Substitutionsgrad Substitutionsmuster Molekulargewicht 450/0,7 70/0,5 200/0,5 200/0,62 130/0,

17 HES - mittleres Molekulargewicht z.b. HES Molekulargewicht (Da) Nierenschwelle bei Molekulargewicht von ca Da

18 HES - Enzymatische Spaltung durch α-1,4-amylase O O 1 1,6- Bindung 6 CH 2 -CH 2 OH O O O O O O O O 1 4 CH 2 -CH 2 OH CH 2 -CH 2 OH CH 2 - CH 2 OH 1,4- Bindung CH 2 -CH 2 OH Abbau abhängig von: 1. Substitutionsgrad (hoch: langsamerer Abbau) 2.Substitutionsmuster C 2 /C 6 3.Molekulargewicht (MG) (hoch: langsamerer Abbau) nur wichtig, wenn MG ca Da (Nierenschwelle)

abhängig von: 1. Substitutionsgrad (hoch: langsamerer Abbau) 2.Substitutionsmuster C 2 /C 6 3.

19 A Vielen Dank für Ihre Aufmerksamkeit

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