On 29 September 2022, EMA’s safety committee (PRAC) recommended new measures to reduce the risk of respiratory failure (severe breathing difficulties that may be life-threatening) and sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage) when using terlipressin-containing medicines in people with type 1 hepatorenal syndrome (type 1 HRS) (serious kidney problems in people with advanced liver disease).

The new measures include adding to the product information a warning to avoid using terlipressin-containing medicines in patients with advanced acute-on-chronic liver disease (liver disease that suddenly worsens) or advanced kidney failure. Patients with breathing problems should receive treatment to manage their condition before starting terlipressin-containing medicines. During and after treatment, patients should be monitored for signs and symptoms of respiratory failure and infection.

In addition, healthcare professionals can consider giving terlipressin-containing medicines as a continuous infusion (drip) into the vein as an alternative to giving it by bolus injection (full dose injected in one go) as this may reduce the risk of severe side effects.

The recommendations follow the PRAC’s review of available data, including results from a clinical trial  involving patients with type 1 HRS which suggested that patients who were treated with terlipressin-containing medicines were more likely to experience and die from respiratory disorders within 90 days after the first dose than those who were given placebo (a dummy treatment).

Although respiratory failure is a known side effect of terlipressin-containing medicines, the frequency of respiratory failure seen in the study was higher (11%) than previously reported in the product information. In addition, the study reported sepsis in 7% of patients in the terlipressin arm compared with none in the placebo group.

There were limitations to the data, such as differences in how terlipressin was used in the clinical trials compared to clinical practice. After considering these limitations together with other available data and consulting an expert group composed of healthcare professionals with expertise in the field of hepatorenal syndrome, PRAC concluded that new measures were needed to ensure that the benefits of terlipressin-containing medicines continue to outweigh the risks.

The PRAC recommendations were sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) which endorsed them and adopted its position on 10 November 2022.