Dear Healthcare Professionals Letter about a restriction of use of hydroxyethyl-starch (HES): Tetraspan, Voluven and Volulyte

14.11.2013

B. Braun Adria d.o.o. and Fresenius Kabi d.o.o., the marketing authorisation holders for hydroxyethyl-starch-containing medicinal products (Tetraspan 60 and 100 mg/ml solution for infusion, Voluven 6% solution for infusion, Volulyte 6% solution for infusion) have in collaboration with the Agency for Medicinal Products and Medical Devices (HALMED) sent out a letter to healthcare professionals about new restrictions of use of hydroxyethyl-starch-containing medicinal products (HES) based on the benefits/risks ratio assessment carried out recently in the EU

Summary

HES-containing medicinal products may be used solely for treatment of hypovolaemia due to acute bleeding when the use of only crystalloids is not considered sufficient.
HES-containing medicinal products should be used in the lowest effective possible dose and in the shortest duration. The treatment should be accompanied by a permanent monitoring of haemodynamics so that the infusion may be stopped when the appropriate haemodynamic effects have been achieved.
HES-containing medicinal products are now contra-indicated in:
- sepsis
- scorches
- renal impairment or renal replacement therapy
- intracranial or cerebral bleeding
- critical patients (in intensive care)
- hyperhydrated patients, including patients with lung oedema
- dehydrated patients
- severe coagulopathy
- heavy impairment of liver function
Clear data about long term safety of use in patients undergone surgery and in patients with injuries are missing. The expected treatment benefit should be carefully weighed regarding the uncertainty of long term use and alternative treatments should be also considered.
Many randomised clinical studies indicate an increased risk of renal impairment in critical patients, including patients with sepsis. The use of HES should be stopped at first appearance of renal impairment and it is strongly advised to monitor the renal function in patients receiving HES. Therefore, HES should not be used anymore in these patients.

Detailed information on safe use

Infusion solutions containing HES belong to class of colloids. In EU Member States these products are authorised nationally.

The results of two clinical trials in critical patients, mainly with sepsis have been recently published. The studies compared the HES treatment with colloids treatment. The studies demonstrate an increased risk of renal adverse reactions in HES treated patients. The investigation patients with sepsis also demonstrates an increased mortality risk in HES treated patients.

Based on the results of these randomised controlled studies, the European Medicines Agency (EMA) initiated in November 2012 a review of safe use of all HES-containing medicinal products in the EU. HALMED was regularly published the information on its webpages during this procedure.

Based on the available data, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) that HES-containing medicinal products should be used only in the aforementioned restricted patient population. Therefore new contra-indications and warnings are being introduced, and marketing authorisation holders are obliged to carry out further studies. The Summary of Product Characteristics and Package Leaflet will be updated with new information.

Here you may see the Dear Healthcare Professional Letter (in Croatian).

HALMED has not received any report to adverse reaction or adverse reaction with lethal outcome associated with use of HES-containing medicines. HALMED will continue monitoring the safe use of HES-containing medicinal products and will inform the public promptly about any new information.

We remind healthcare professionals that they should report any adverse reaction to HALMED, as well as quality defect. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED via form or on-line application, with recommendation regarding any adverse reaction they discover to consult with their doctor or pharmacist about the continuation of their therapy.

The previously published information about safety reviews of use of HES-containing medicinal products are available under the folowing links: