Summary Safety Review - Soliris (eculizumab) - Assessing the Potential Risk of Drug-induced Liver Injury

Soliris (eculizumab)

Drug-induced liver injury (DILI), a rare, but potentially life-threatening drug reaction with elevated liver enzymes that may lead to liver failure or a need for liver transplant

• Soliris (eculizumab) is authorized for sale in Canada to treat patients with various disorders, including a type of rare blood disorder (paroxysmal nocturnal hemoglobinuria), and immune conditions affecting small blood vessels (atypical hemolytic uremic syndrome), muscles (generalized myasthenia gravis) and the central nervous system (neuromyelitis optica spectrum disorder).

• Health Canada reviewed the potential risk of DILI with the use of Soliris. The safety review was triggered by Canadian and international case reports published in the scientific literature concerning this risk.

• At the time of the review, the Canadian product monograph (CPM) for Soliris included the risk of elevated liver enzymes, but not specifically DILI.

• Health Canada’s review of the available information did not find sufficient evidence to support a link between the risk of severe DILI and the use of Soliris. The cases reviewed described increases in liver enzymes, and were diagnosed as mild or moderate DILI. It was determined that the existing product safety information in the CPM is appropriate. Therefore, no updates are needed at this time.

• Health Canada will continue to monitor the safety of Soliris.

Health Canada reviewed the potential risk of DILI with the use of Soliris. The safety review was triggered by Canadian and international case reports published in the scientific literature concerning this risk.

Drug-induced liver injury is a rare, but potentially life-threatening drug reaction with elevated liver enzymes that may lead to serious outcomes such as liver failure or a need for liver transplant.

At the time of the review, the CPM for Soliris included the risk of elevated liver enzymes, but not specifically DILI.

• Soliris is a prescription drug authorized for sale in Canada to treat patients with various disorders, including a type of rare blood disorder (paroxysmal nocturnal hemoglobinuria), and immune conditions affecting small blood vessels (atypical hemolytic uremic syndrome), muscles (generalized myasthenia gravis) and the central nervous system (neuromyelitis optica spectrum disorder).

• Soliris has been marketed in Canada since 2009. It is currently available as a solution for infusion into a vein (intravenous).

• The number of prescriptions for Soliris increased from 960 in 2016 to approximately 14,780 in 2021.

• Health Canada reviewed information provided by the manufacturer, and from searches of the Canada Vigilance database^a, the World Health Organization’s adverse drug reaction database^b and the scientific literature.

• Health Canada reviewed 58 cases (6 Canadian and 52 international) of DILI in patients using Soliris. Of those 58 cases, 2 (1 Canadian) were found to be probably linked to the use of Soliris, 5 (3 Canadian) were found to be possibly linked and 51 (2 Canadian) were unlikely to be linked.

• All 7 cases found to be probably or possibly linked to the use of Soliris were considered either mild or moderate in severity, and reported only increased liver enzymes. There were no cases of liver failure or other serious outcomes. All 7 cases resolved during treatment (2 cases) or after discontinuation of the drug (5 cases).

• Health Canada’s review of the scientific literature did not find any published studies that showed an increased risk of DILI with serious outcomes in patients treated with Soliris.

• Health Canada's review of the available information did not find sufficient evidence to support a link between the risk of severe DILI and the use of Soliris. The cases reviewed described increases in liver enzymes, and were diagnosed as mild or moderate DILI. It was determined that the existing product safety information in the CPM is appropriate. Therefore, no updates are needed at this time.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of Soliris and other health products to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving Soliris, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

The analysis that contributed to this safety review included scientific literature, Canadian and international information, and what is known about the use of Soliris both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Canadian reports can be accessed through the Canada Vigilance Online Database.

2. World Health Organization’s adverse drug reaction database