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The United States: Serious liver injury being observed in patients without cirrhosis taking Ocaliva (obeticholic acid) to treat primary biliary cholangitis (English only)
 
The United States Food and Drug Administration (FDA) identified cases of serious liver injury among patients being treated for primary biliary cholangitis (PBC) with Ocaliva (obeticholic acid) who did not have cirrhosis of the liver, based on its review of postmarket clinical trial data. FDA previously identified that PBC patients with advanced cirrhosis were at risk of serious liver injury when taking Ocaliva and updated the prescribing information to restrict its use in these patients. FDA’s review of this required clinical trial found that some cases of liver injury in patients without cirrhosis resulted in liver transplant. This risk was notably higher for patients taking Ocaliva compared with a placebo, a pill without any active medicine.

FDA restricted the use of Ocaliva in patients who have PBC with advanced cirrhosis of the liver in 2021 because it can cause serious harm in those patients, adding a new Contraindication to the Ocaliva prescribing information and patient Medication Guide. However, recent review of case reports submitted to FDA found that some patients with PBC and advanced cirrhosis were still taking the medicine despite these restrictions.

Ocaliva is a prescription medicine approved in May 2016 that has been shown to improve a certain liver test called alkaline phosphatase (ALP) in patients with PBC who have not responded well enough to another medicine called ursodeoxycholic acid (UDCA). The original clinical trial showed a decrease in ALP that supported FDA accelerated approval. FDA required the additional postmarket clinical trial to verify the clinical benefit of Ocaliva.

FDA evaluated liver safety in the postmarket clinical trial in patients who were appropriate for Ocaliva treatment based on the approved indication in the prescribing information. Among these patients, the risk of both liver transplant and death were higher in patients receiving Ocaliva compared with those receiving placebo. Specifically, among patients for whom Ocaliva was indicated, which were those with a lower risk of progression to liver transplant or death, 7 of 81 who received Ocaliva needed a liver transplant compared to 1 of 68 patients who received placebo. An additional four patients receiving Ocaliva died, compared to one receiving placebo. Analyses evaluating the risk of liver transplant and death resulted in a hazard ratio of 4.77 (95% confidence interval: 1.03, 22.09) for patients without advanced cirrhosis and not contraindicated from receiving the drug.

Following the addition of the contraindication for PBC patients with advanced cirrhosis in May 2021, FDA identified 20 cases (domestic, n=13; foreign, n=7) received between May 26, 2021, and September 18, 2024, reporting one or more of the following events in patients treated with Ocaliva: liver transplant (n=7), evaluation or listing for liver transplant (n=8), or liver-related death (n=6). Although FDA was not able to assess the appropriateness of Ocaliva use for most of these cases because of limited information, it identified three U.S. cases of liver-related events that occurred in patients for whom Ocaliva should have been discontinued based on progression of their liver disease as indicated in the 2021 safety labeling changes. This shows the importance of ongoing monitoring of liver tests and prompt action to withdraw Ocaliva if there is evidence of progression towards cirrhosis.

FDA previously communicated about the risk of serious liver injury associated with Ocaliva in May 2021 (restriction of Ocaliva use in PBC patients with advanced cirrhosis). Additional communications about related safety issues for Ocaliva occurred in February 2018 (addition of Boxed Warning to highlight correct dosing of Ocaliva) and September 2017 (warning about serious liver injury with incorrect dosing).

Healthcare professionals should monitor liver tests frequently in patients being treated with Ocaliva to detect and address worsening liver function early. Based on the current data, it is not clear if this monitoring will be sufficient to address the risk of serious liver injury. Discontinue Ocaliva treatment with any evidence of liver disease progression or if efficacy is not established. Explain the signs and symptoms of worsening liver injury to patients receiving Ocaliva and direct them to contact healthcare professionals immediately if they develop any signs or symptoms of worsening liver injury.

Please refer to the following website in FDA for details: http://www.fda.gov/drugs/drug-safety-and-availability/serious-liver-injury-being-observed-patients-without-cirrhosis-taking-ocaliva-obeticholic-acid-treat

In Hong Kong, the above product is not a registered pharmaceutical product. Related news was previously issued by FDA, Medicines and Healthcare products Regulatory Agency, Health Canada and European Medicines Agency, and was posted on the Drug Office website since 22 Sep 2017, with the latest update posted on 29 Jun 2024.

Ends/Friday, Dec 13, 2024
Issued at HKT 15:00
 
Related Information:
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Canada: OCALIVA (obeticholic acid): New contraindication for the treatment of pr... 上載於 2022-12-06
The United States: FDA restricts use of Ocaliva in primary biliary cholangitis (... 上載於 2021-05-27
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美國:Ocaliva (奧貝膽酸):藥物安全通訊:增加黑框警告以突出正確劑量 上載於 2018-02-02
美國:食物及藥物管理局藥物安全通訊:食物及藥物管理局警告罕見慢性肝病藥物Ocaliva (奧貝膽酸)與嚴重肝臟損害 上載於 2017-09-22
 
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