Other safety alerts
|
| |
| The United Kingdom: Ivacaftor, tezacaftor, elexacaftor (Kaftrio▼) in combination with ivacaftor (Kalydeco): risk of serious liver injury; updated advice on liver function testing |
| |
Medicines and Healthcare products Regulatory Agency (MHRA) announces that cases of serious liver injury with elevated transaminases and bilirubin have been reported during treatment with Kaftrio–Kalydeco combination therapy.
A recent European review of safety data identified a case of liver failure leading to liver transplantation in a patient taking Kaftrio–Kalydeco combination. This case was reported post-marketing in an adult patient with pre-existing cirrhosis and portal hypertension. The review also identified 2 other cases of serious liver injury in adult patients with no prior history of liver disease. These patients had elevations in transaminases and total bilirubin, and the patients were hospitalised with jaundice. It is not possible to estimate the frequency of reports of serious liver injury or bilirubin elevations. The mechanism underlying liver injury following treatment is also unknown.
In the United Kingdom, from Oct 2020 and up to 12 Dec 2021, the Yellow Card scheme has received 22 reports of serious liver disorders and 54 reports of abnormal liver test results (6 with concomitant bilirubin elevations) associated with Kaftrio–Kalydeco combination therapy.
Following the findings of the European review, existing warnings on hepatotoxicity in the product information for Kaftrio and Kalydeco have been strengthened to include the risk of clinically relevant drug-induced liver injury with Kaftrio–Kalydeco combination therapy. The recommendations for liver function monitoring before and during treatment, which already included regular assessment of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), have been strengthened to include advice to measure total bilirubin concomitantly. The advice that more frequent monitoring should be considered in patients with a history of transaminase elevations has been extended to include also patents with pre-existing liver disease. In patients with pre-existing advanced liver disease (for example, cirrhosis, portal hypertension) Kaftrio–Kalydeco combination therapy should be used with caution and only if the benefits are expected to outweigh the risks. If these patients receive combination therapy, they should be closely monitored after the initiation of treatment.
Advice for healthcare professionals:
- Cases of serious liver injury characterised by concomitant elevations in ALT, AST, and total bilirubin have been reported with ivacaftor/tezacaftor/elexacaftor (Kaftrio) in combination with ivacaftor (Kalydeco).
- One case of serious liver injury in a patient with pre-existing cirrhosis and portal hypertension resulted in liver failure requiring liver transplantation.
- Measure total bilirubin levels in addition to ALT and AST levels before initiating treatment, every 3 months during the first year of treatment, and annually thereafter; consider more frequent monitoring for patients with a history of liver disease or a history of transaminase elevations.
- Use with caution in patients with advanced pre-existing liver disease (for example, cirrhosis or portal hypertension) and only if the benefits are expected to outweigh the risks; if used, these patients should be closely monitored.
- perform prompt clinical evaluation and measure liver function in patients who report symptoms that may indicate liver injury.
- Discontinue treatment in the event of significant elevation of liver enzymes or clinical signs and symptoms of liver injury; following resolution of liver abnormalities, consider the benefits and risks before resuming treatment.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/ivacaftor-tezacaftor-elexacaftor-kaftriov-in-combination-with-ivacaftor-kalydeco-risk-of-serious-liver-injury-updated-advice-on-liver-function-testing
In Hong Kong, there is no registered pharmaceutical product containing ivacaftor, tezacaftor or elexacaftor.
Ends/Wednesday, Feb 16, 2022
Issued at HKT 14:30
|
| |
