On 11 February 2022, the EMA Safety Committee, PRAC, recommended the suspension of marketing authorisations for hydroxyethyl starch (HES) infusion solutions in the European Union. These products were licensed as an add-on therapy for plasma volume replacement following acute (sudden) blood loss.
The safety of HES infusion solutions was evaluated in two separate procedures in the year 2013, and a number of restrictions and measures were implemented to minimize the risk of kidney injury and death in certain patients (those in critical condition, with burns, or with sepsis, a bacterial infection in the blood).
As a result of a third review conducted in the year 2018, the use of HES infusion solutions was further restricted to accredited nursing homes and healthcare professionals prescribing or administering the drugs had to be trained in their appropriate use. In addition, further warnings were introduced in the product information to remind healthcare professionals that these medicines should not be used in patients with sepsis or renal impairment or in other vulnerable patients, such as the critically ill. These measures were implemented to ensure that HES infusion solutions were not used in patients at increased risk of harm. Companies marketing HES solutions for infusion were also asked to conduct a drug utilisation study to check whether these restrictions were observed in clinical practice, and to submit the results of this study to the EMA.
The PRAC evaluated the results of this study, which show that HES solutions for infusion continue to be used outside the recommendations included in the product information. The PRAC concluded that the further restrictions introduced in 2018 did not adequately ensure the safe use of the medicines and that HES solutions continue to be used in some patient groups in whom serious harm has been demonstrated.
Given that adherence to the package of measures agreed in 2018 was a prerequisite for the safe use of HES infusion solutions, and the study showed that this was not the case, the benefits of these medicines are no longer considered to outweigh their risks. The PRAC explored the possibility of introducing additional measures to ensure that HES infusion solutions are used in accordance with the product information, but concluded that there were no other measures or combination of measures that would be feasible and sufficient to protect patients.
Due to the serious risks to which certain patient populations continue to be exposed, the PRAC recommended the suspension of marketing authorisations for HES infusion solutions in the EU.
PRAC's recommendation was sent to the Mutual Recognition and Decentralised Procedures Coordination Group (CMDh), which adopted its recommendation on 23 February 2022.
Patient information
- HES infusion solutions are replacement fluids administered to patients with blood loss following injury or surgery.
- The EMA recommends removing these medicines from the EU market because of the serious risks (kidney damage and death) in certain patients (for example, those who are severely ill or have blood poisoning).
- Other treatment options are available.
Information for healthcare professionals
- It is recommended that the marketing authorization for HES solutions for infusion be suspended due to the risk of renal impairment and death in certain patient populations, including critically ill patients and patients with sepsis.
- Despite the introduction of contraindications and warnings in 2013 and further measures in 2018, the most recent drug utilisation study shows that HES infusion solutions continue to be used outside the recommendations included in the product information, which continues to expose certain patient populations to serious risks.
- As no other feasible and effective measures to minimise the risks can be identified, the EMA recommends suspending the marketing authorisation of HES infusion solutions from the EU market to protect patient health.
- Alternative therapies are available and should be selected in accordance with relevant clinical guidelines.
A direct communication to healthcare professionals (DHPC) will be sent to the healthcare professionals involved in due course. The DHPC will also be published on a dedicated page on the EMA website.
More about the drug
HES infusion solutions were licensed for the treatment of hypovolemia (low blood volume) caused by acute blood loss, where treatment with alternative infusion solutions known as "crystalloids" alone is not considered sufficient.
HES solutions belong to a class of drugs known as colloids. In addition to blood products, there are two types of drugs used to replace plasma volume: crystalloids and colloids. Colloids contain large molecules such as starch, whereas crystalloids are solutions of low molecular weight substances and include saline and Ringer's solutions.
In the EU, HES solutions for injection are licensed through national procedures and are available in several Member States under various trade names.
More about the process
The EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which is responsible for evaluating safety issues for medicinal products for human use, issued its recommendation following its assessment of the results of the drug utilisation study requested as part of the additional risk minimisation measures resulting from the completion of the Article 107i referral process in 2018.
PRAC's recommendation was sent to the Mutual Recognition and Decentralised Procedures Coordination Group (CMDh). The CMDh, also taking into account additional information on HES infusion solutions from marketing authorisation holders and external parties, endorsed the PRAC recommendation and adopted its position. As the CMDh position was adopted by a majority, it will now be sent to the European Commission, which will take a legally binding decision for the whole EU in due course.
The CMDh is a body representing the EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised through national procedures across the EU.
(AΦ)
Contents of this article including associated images are owned by PIO
Views & opinions expressed are those of the author and/or PIO
Source
