Restriction of use of hydroxyethyl starch instead of a withdrawal from the market - niche indication with insufficient supporting data: After a complicated procedure, in October the Pharmacovigilance Risk Assessment Committee (PRAC) revoked its recommendation of June 2013 to remove solutions for infusion with hydroxyethyl starch (HES; e.g. HAES-STERIL) from the market across the European Union (a-t 2013; 44: 63) (1):* According to the new PRAC recommendation (2), HES will stay on the market but can be used only in very limited circumstances. In future the solutions will be contraindicated in critically ill patients and in patients with sepsis or burns because of an increased risk of kidney damage and mortality as well as in patients with renal insufficiency. The only remaining indication is hypovolaemia caused by acute blood loss if crystalloid solutions alone are not considered to be sufficient (1). However, the PRAC acknowledged that the evidence for this niche indication, which can affect surgical or trauma patients, is very limited: The available data are from small studies with short follow-up periods, according to which HES is thought to be more beneficial than crystalloid solutions especially with regard to haemodynamic surrogate parameters. The PRAC did not cite any convincing evidence of clinically relevant benefits of the starch solution in this patient population in its assessment report (3) published in November. No reliable statements regarding the safety of HES for the remaining niche indication can be made either on the basis of the available data. The PRAC is therefore requesting that suppliers conduct large randomized studies in surgical and/or trauma patients which are designed to assess mortality and renal toxicity after 90 days. The study protocols are to be completed within six months of the European Commission's decision about the marketing authorisation status of HES, which is still pending, and the results are to be available by the end of 2016 (3). In an open letter written in early November to the EMA, 75 international intensive care physicians protested against the revision of the original PRAC recommendation. The authors rightly ask about clinical data which ensure that the risks of HES observed in critically ill patients, especially renal toxicity, risk of bleeding and higher mortality, do not affect patients with hypovolaemia alone. The intensive care physicians even dispute the ethical acceptability of further studies with HES considering what is currently known (4). We continue to support the removal of starch solutions from the market, but if they stay on the market, in our opinion they should be used for the outcomes studies requested by the PRAC only. -Ed.

1

EMA: press release, as at 25 Oct. 2013; http://www.ema.europa.eu/docs/en_GB/document_library/ Referrals_document/Hydroxyethyl_starch-containing_medicines_107/Position_provided_by_CMDh/WC500153118.pdf

2

EMA: Assessment report for solutions for infusion containing hydroxyethyl starch (Article 31), as at 11 Nov. 2013; http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/ Solutions_for_infusion_containing_hydroxyethyl_starch/Recommendation_provided_by_ Pharmacovigilance_Risk_Assessment_Committee/WC500154414.pdf

3

EMA: Assessment report for solutions for infusion containing hydroxyethyl starch (Article 107i), as at 11 Nov. 2013; http://www.ema.europa.eu/docs/en_GB/document_library/ Referrals_document/Hydroxyethyl_starch-containing_medicines_107/ Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee/WC500154254.pdf

4

BELLOMO, R. et al.: Open Letter to the Executive Director of the European Medicines Agency concerning the licensing of hydroxyethyl starch solutions for fluid resuscitation, 4 Nov. 2013

*

Due to the manufacturers' objections on the one hand and the British medicines agency's withdrawal from the market of HES on the basis of the PRAC recommendation on the other hand, the PRAC recommendation had to be reviewed in two parallel procedures in accordance with the legal provisions (1). In the first procedure the PRAC confirmed its original recommendation to remove it from the market (2), in the second, after consulting additional literature and a holding a new hearing with experts, it voided it.