Hydroxyethyl starch (Voluven and Volulyte)

Consumers and health professionals are advised that a subsequent review of the safety issue relating to hydroxyethyl starch-containing medicines has resulted in updated information for the below safety advisory.

In addition to the potential risks for patients with sepsis (detailed below), the updated review found that the increased risk of death and kidney injury that may need kidney replacement therapy (such as dialysis) applies to all critically ill patients, such as those typically admitted to the intensive care unit of a hospital.

In response to the new information, the TGA has been working closely with Fresenius Kabi Australia, the sponsor of the two hydroxyethyl starch products, Voluven and Volulyte, to update the Product Information (PI) for these medicines.

The TGA will continue to monitor this issue.

Information for health professionals

Information about this safety issue provided below for health professionals remains largely appropriate. However, please note that the updated PI now includes:

• a new contraindication: ‘Critically ill patients (typically admitted to intensive care unit), including those with sepsis’
• a black boxed warning: ‘The use of [hydroxyethyl starch] in critically ill patients, including those with severe sepsis, is associated with an increased risk of death or the need for renal replacement therapy’

The evaluation of these risks is mainly based on the publication of the VISEP, 6S and Chest studies.^1,2,3

The TGA is continuing to work with Fresenius Kabi Australia regarding this issue.

Information for consumers

Information about this safety issue provided below for consumers remains appropriate. However, please note that the updated PI now contraindicates use in critically ill patients (not just those with sepsis).

If you have any questions or concerns about this issue, talk to your health professional.

References

1. VISEP - Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358:125-139
2. 6S - 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;367:124-134
3. CHEST - Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367:1901-1911

Safety advisory - increased risk of mortality and the need for dialysis in patients with sepsis

4 April 2014

Consumers and health professionals are advised that a recent safety review of hydroxyethyl starch has found an increased risk of mortality and the need for dialysis when this medicine is used to treat patients with sepsis (see ‘Update’ above for new information).

Hydroxyethyl starch is used in clinical situations, including during surgery, to treat and prevent a condition known as hypovolaemia.

In Australia, two products that contain hydroxyethyl starch are registered on the Australian Register of Therapeutic Goods - Voluven and Volulyte.

Prior to undertaking the full safety review, the TGA published a monitoring communication for hydroxyethyl starch as part of its Early Warning System.

Since then, the TGA has worked with the Australian sponsor of Voluven and Volulyte, Fresenius Kabi Australia, to update the Product Information (PI) for these medicines. The updated PI, which included new contraindications for 'patients with sepsis' and 'patients with severe liver disease', as well as updated information in the precautions and dosage and administration sections, was approved on 12 July 2013.

The TGA's safety review, which considered information provided by Fresenius Kabi Australia and open literature regarding the safety of hydroxyethyl starch, found that the updates in the PI regarding patients with sepsis were sufficient to mitigate the identified risks.

For non-septic patients, no evidence of increased risk of mortality or the need for dialysis was identified (see ‘Update’ above for new information).

The TGA will continue to monitor this issue.

Information for health professionals

Health professionals should ensure that they are familiar with the current PI for hydroxyethyl starch. In particular, note that this medicine is now contraindicated for patients with sepsis and patients with severe liver disease (see ‘Update’ above for new information).

Hydroxyethyl starch should be discontinued at the first sign of renal injury or if coagulopathy is detected. Use in critically ill patients should only be considered if other therapies have failed, the lowest possible dose is chosen, and the benefits outweigh the risk (see ‘Update’ above for new information).

If a patient is concerned about this issue, reassure them that the PI update addresses the above risks.

Information for consumers

Hydroxyethyl starch is used in very specific circumstances, most commonly in hospitals during surgery and in other circumstances where there is a sudden drop in blood pressure and intravenous fluid replacement is required.

The PI update, including ruling out use of this medicine for patients with sepsis, addresses the above risks (see ‘Update’ above for new information).

If you have any concerns about this issue, talk to your health professional.

Reporting problems

Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.

The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.