Hydroxyethyl starch solutions for infusion

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
European Commission final decision

Overview

Hydroxyethyl-starch solutions (HES) no longer to be used in patients with sepsis or burn injuries or in critically ill patients

HES will be available in restricted patient populations

On 23 October 2013, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)*, endorsed by majority the recommendations of the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC), which concluded that HES solutions must no longer be used to treat patients with sepsis (bacterial infection in the blood) or burn injuries or critically ill patients because of an increased risk of kidney injury and mortality.

HES solutions may continue to be used in patients to treat hypovolaemia (low blood volume) caused by acute (sudden) blood loss, where treatment with alternative infusions solutions known as 'crystalloids' alone are not considered to be sufficient. In order to minimise potential risks in these patients, HES solutions should not be used for more than 24 hours and patients' kidney function should be monitored after HES administration. In addition to updating the product information, further studies should be carried out on the use of these medicines in elective surgery and trauma patients.

The review of HES solutions was carried out by the PRAC following the publication of studies showing an increased risk of mortality in patients with sepsis1,2 and an increased risk of kidney injury requiring dialysis in critically ill patients1,2,3 following treatment with HES solutions.

As the CMDh position was adopted by majority vote, it was sent to the European Commission, which endorsed it and, on 19 December 2013, adopted a final legally binding decision valid throughout the European Union (EU).


Information for patients

  • Because of the risk of kidney injury and mortality, HES solutions must no longer be used in patients with sepsis (bacterial infection in the blood) or burn injuries or critically ill patients.
  • HES solutions may continue to be used to treat hypovolaemia (low blood volume) caused by acute (sudden) blood loss. However, the doctor should monitor the patient's kidney function after HES administration.
  • Patients who have any questions or concerns should speak to the treating doctor, pharmacist or nurse.

Information for healthcare professionals

  • Because of the risk of kidney injury and mortality, HES solutions must no longer be used in patients with sepsis, burn injuries or critically ill patients.
  • HES solutions should only be used for the treatment of hypovolaemia due to acute blood loss when crystalloids alone are not considered sufficient.
  • There is a lack of robust long-term safety data in patients undergoing surgical procedures and in patients with trauma. The expected benefit of treatment should be carefully weighed against the uncertainties with regard to long-term safety, and other available treatment options should be considered. Additional studies will be performed with HES solutions in patients with trauma and in elective surgery.
  • HES solutions should be used at the lowest effective dose for the shortest period of time. Treatment should be guided by continuous haemodynamic monitoring so that the infusion is stopped as soon as appropriate haemodynamic goals have been achieved.
  • HES solutions are now contraindicated in patients with renal impairment or renal replacement therapy. The use of HES must be discontinued at the first sign of renal injury. An increased need for renal replacement therapy has been reported up to 90 days after HES administration. Patients' kidney function should be monitored after HES administration.
  • HES solutions are contraindicated in severe coagulopathy. HES solutions should be discontinued at the first sign of coagulopathy. Blood coagulation parameters should be monitored carefully in case of repeated administration.
    These recommendations are based on a review of all available safety and efficacy data, including recent data4,5,6, from clinical studies, meta-analyses and post-marketing experience. Healthcare professionals have been informed in writing of the outcome of the review and the changes to the use of HES solutions.

References:

  1. Perner A, Haase N, Guttormsen AB et al. Hydroxyethyl starch 130/0.42 versus ringer's acetate in severe sepsis. N Engl J Med 2012;367(2):124-34
  2. Brunkhorst FM, Engel C, Bloos F et al. Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis. N Engl J Med 2008; 358(2):125-39
  3. Myburgh J, Finder S, Bellomo R et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367:1901-11
  4. Annane D. et al. CRISTAL: Colloids Compared to Crystalloids in Fluid Resuscitation of Critically Ill Patients: A Multinational Randomised Controlled Trial. NCT00318942. Available on: http://clinicaltrials.gov/ct2/show/NCT00318942
  5. Siegemund M. Firstly presented at European Society of Anaesthesiology conference 2012. Basel Study for Evaluation of Starch (130;0.4) Infusion in Septic Patients:BaSES (130;0.4) Trial, listed at http://clinicaltrials.gov/show/NCT00273728
  6. Rational Fluid Therapy in Germany (RaFTinG). Available on ClinicalTrials.gov (NCT01122277) last updated on 07 July 2011: http://clinicaltrials.gov/ct2/show/NCT01122277?term=NCT01122277&rank=1

Key facts

About this medicine
Approved name
Hydroxyethyl starch solutions for infusion
International non-proprietary name (INN) or common name
hydroxyethyl starch
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-107i/1376
Type
Article 107i procedures

This type of procedure is triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue. Situations that fall under this procedure include consideration for suspension or revocation of the marketing authorisation for a medicine, the prohibition of supply of a medicine or major changes to the marketing authorisation such as deletion of indications, reduction of the recommended dose or new contraindications. The procedure is also applicable in case of a safety issue with a class of medicines.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
11/07/2013
PRAC recommendation date
10/10/2013
CHMP opinion/CMDh position date
23/10/2013
EC decision date
19/12/2013
Outcome
Risk minimisation measures

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations and the general public) to submit data relevant to this procedure. This is in accordance with Article 107j(1) of Directive 2001/83/EC.

The following requirements apply for data to be considered:

Submitting data

Send the completed form electronically to the stakeholders' submission inbox (public@ema.europa.eu). Specify the name of the medicine in the subject line of the e-mail.

The size of the submission file should not exceed 25 MB. If your attempt to send your data package to the dedicated e-mail address is unsuccessful, please use alternative submission means.

It is of the utmost importance that data are provided promptly, to avoid undermining the safety review. Due to the urgent nature of the procedure, you are strongly advised to submit your data in English.

Protection of personal data

Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001. They will be treated in accordance with the specific PDF iconprivacy statement for public consultations .

Treatment and publication of data

Data submitted will be received and recorded by the Agency.

The Agency will prepare a list of all submissions received, which will be published as an annex to the PRAC assessment report for transparency purposes and public awareness.

Please note that all data submitted in the context of this procedure may be shared and disclosed in the public domain.

All documents

Procedure started

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Position provided by CMDh

  • List item

    Hydroxyethyl starch Article-107i procedure - Annex I (PDF/704.94 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014

  • List item

    Hydroxyethyl starch Article-107i procedure - Annex II (PDF/65.28 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014

  • List item

    Hydroxyethyl starch Article-107i procedure - CMDh divergent position (PDF/45.52 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014

  • List item

    Hydroxyethyl starch Article-107i procedure - Annex IV (PDF/32.62 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014

  • List item

    Hydroxyethyl starch Article-107i procedure - Annex III (PDF/129.63 KB)


    First published: 25/10/2013
    Last updated: 06/03/2014

  • List item

    Hydroxyethyl-starch solutions (HES) should no longer be used in patients with sepsis or burn injuries or in critically ill patients – CMDh endorses PRAC recommendations (PDF/81.32 KB)


    First published: 25/10/2013
    Last updated: 25/10/2013
    EMA/640658/2013

  • European Commission final decision

  • List item

    Hydroxyethyl-starch solutions (HES) no longer to be used in patients with sepsis or burn injuries or in critically ill patients (PDF/92.16 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014
    EMA/809470/2013

  • List item

    Hydroxyethyl-starch solutions (HES) no longer to be used in patients with sepsis or burn injuries or in critically ill patients (PDF/92.16 KB)


    First published: 06/03/2014
    Last updated: 06/03/2014
    EMA/809470/2013

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

    How useful was this page?

    Add your rating