Summary Safety Review - Direct-acting antivirals - Assessing the Potential Risk of Hepatitis B Virus Reactivation
December 1, 2016
Direct-acting antivirals (DAAs)
Potential Safety Issue
Hepatitis B virus (HBV) reactivation
- Direct-acting antivirals (DAAs) are drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection, a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) and liver cancer.
- Health Canada carried out a review of the potential risk of hepatitis B virus (HBV) reactivation with the use of DAAs. The review was triggered by reports that patients infected with both HBV and HCV may experience a reactivation of their HBV infection if DAAs are used to treat their HCV infection. These reports were identified by the European Medicines Agency (EMA).
- Health Canada's review concluded that there is a potential risk of HBV reactivation in patients co-infected with both HBV and HCV, and the use of DAAs. Health Canada has recommended that the safety information for all DAAs be updated to inform about this potential risk.
Health Canada carried out this safety review after becoming aware of reports of HBV reactivation in patients infected with both HBV and HCV treated with DAAs. Reactivation refers to the return of an active infection and, in the case of HBV, it can lead to serious complications such as liver disease (hepatitis).
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 and they contain either a single DAA or multiple DAAs together: Daklinza (daclatasvir), Sovaldi (sofosbuvir), Harvoni (sofosbuvir, ledipasvir), Epclusa (sofosbuvir, velpatasvir), Holkira Pak (dasabuvir, paritaprevir, ombitasvir, ritonavir), Technivie (paritaprevir, ombitasvir, ritonavir), Galexos (simeprevir), Sunvepra (asunaprevir), and Zepatier (grazoprevir, elbasvir).
- The first DAA available in Canada was Galexos (simeprevir), introduced in 2013.
Safety Review Findings
- At the time of the review, Health Canada had not received any Canadian reports of HBV reactivation related to DAA use in patients infected with both HBV and HCV.
- A total of 13 international reports of HBV reactivation were retrieved from different sources. Of these, 12 reports were considered to be possibly related to the use of these DAAs: 11 reports where sofosbuvir or sofosbuvir with ledipasvir was used and one report where daclatasvir was used. The remaining report (with sofosbuvir use) could not be reviewed further because it did not provide enough information. Of the reports, 3 described symptoms of moderate HBV reactivation. One of the cases reported severe HBV reactivation resulting in liver failure and the patient needed a liver transplant.
- Potential processes have been proposed in the scientific literature to explain how HBV infection could become reactivated in patients that are being treated for their HCV infection.
- Two studies of the use of DAAs in patients infected with both HCV and HBV reported an increase in viral genes (HBV DNA) in some of the patients. This could lead to a reactivation of the HBV infection.
Conclusions and Actions
- Health Canada's review concluded that there may be a link between the risk of HBV reactivation in patients infected with both HBV and HCV that have been treated with certain DAAs.
- Health Canada has recommended that the safety information for all DAAs be updated to inform about this risk, as a precaution. In addition, an Information Update will be published to further inform Canadians and health care professionals.
- 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 adverse reaction reports and what is known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.