Summary Safety Review - Direct-Acting Antivirals - Assessing the Potential Risk of New or Returning Liver Cancer named Hepatocellular Carcinoma
A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.
Direct-acting antivirals (DAAs)
Potential Safety Issue
Potential risk of new or returning liver cancer (Hepatocellular Carcinoma)
Use in Canada
- DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection in adult patients.
- This review included the following products available in Canada, which contain one or many DAAs together: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir), Zepatier (grazoprevir, elbasvir) and Maviret (glecaprevir, pibrentasvir).
- The first DAA was authorized for sale in Canada in 2013.
- About 140,000 prescriptions for DAAs have been given to Canadian patients in 2018.
Safety Review Findings
- Following the review completed in 2017, Health Canada received a total of 125 reports (86 Canadian reports and 39 international published reports of new or returning HCC). Of these 125 reports, 41 cases of new or returning HCC were found to have a possible link with the use of DAAs. However, these reports presented limited information and did not include information on other factors that could contribute to new or returning HCC. Furthermore, based on the information provided, it was difficult to rule out the presence of HCC prior to treatment with DAAs. These limitations prevented Health Canada from establishing a link between new or returning HCC with the use of DAAs.
- A search in Vigibaseb, the World Health Organization's Adverse Drug Reaction Database, found 1669 cases related to new or returning HCC in patients treated with DAAs. There was not enough information in these reports to make a link between the use of DAAs and HCC.
- This safety review also looked at scientific literature published following the review in 2017. Health Canada reviewed a total of 70 studies, of which 59 involved patients. Overall, the reviewed literature did not support a link between the use of DAAs and an increased risk of new or returning HCC in patients who have been treated for HCC.
Conclusions and actions
- Health Canada's 2019 review of the available information did not make a link between the use of DAAs and new or returning HCC.
- Health Canada will continue to monitor safety information involving DAAs, 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 if and when any new health risks are identified.
The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of these medications both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
- Canadian reports can be accessed through the Canada Vigilance Online Database.
- VigiBase is the WHO global database of individual case safety reports. This information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. This information does not represent the opinion of the World Health Organization.