Summary Safety Review - Direct-Acting Antivirals - Assessing the Potential Risk of Liver Cancer Recurrence

April 27, 2017

Product

Direct-acting antivirals (DAAs)

Potential Safety Issue

Liver cancer recurrence

Key Messages

  • Direct-acting antivirals (DAAs) are prescription drugs authorized for sale in Canada to treat chronic hepatitis C virus (HCV) infection in adult patients, which is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) or liver cancer.
  • Health Canada reviewed the potential risk of liver cancer coming back (recurrence) with the use of DAAs, following the publication of a studyFootnote 1 suggesting this potential risk.
  • Health Canada’s review concluded that there was not enough information to establish a link between DAAs and liver cancer recurrence. Health Canada has requested additional safety information from some manufacturers of DAAs.

Overview

Health Canada reviewed the potential risk of liver cancer recurrence with the use of DAAs, following the publication of a studyFootnote 1 suggesting this potential risk.

Use in Canada

  • DAAs are prescription drugs authorized for sale in Canada to treat chronic HCV infection in adult patients, which is a serious condition that can result in decreased liver function, serious scarring of the liver (cirrhosis) or liver cancer.
  • The review included the following products available in Canada which 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 received 3 unique Canadian reports of liver cancer recurrence related to DAAs use (2 with Sovaldi and 1 with Holkira Pak). All 3 reports were considered to be related to the use of DAAs. However, other factors present in the cases may have played a role in the liver cancer recurrence, such as serious scarring of the liver (cirrhosis), previous history of liver cancer and other treatments known to be associated with a higher risk of liver cancer recurrence, including surgery and a cancer treatment using radio waves (radiofrequency ablation).
  • This safety review also looked at information from 14 international reports of liver cancer recurrence related to DAAs use: 9 reports involved Sovaldi, 4 reports involved Harvoni and 1 report involved Holkira Pak. All 14 reports were considered to be related to DAAs use. However, factors known to be associated with a higher risk of liver cancer recurrence may have played a role.
  • A search of the scientific literature identified 7 relevant studies describing the recurrence of liver cancer related to DAA use. The safety review could not conclude whether the use of DAAs played a role because the lengths of time the patients were monitored were different between the studies. The patients also had a variety of risk factors for liver cancer, including HCV infection, cirrhosis, previous history of liver cancer and advanced age.
  • Some studies have found that liver cancer recurrence was more likely to happen in patients who underwent surgery or radiofrequency ablation compared to those patients that received a liver transplantFootnote2.

Conclusions and Actions

  • Health Canada’s review concluded that there was not enough information to establish a link between DAAs and liver cancer recurrence. Health Canada has also requested additional safety information from manufacturers of DAAs regarding this risk as it becomes available.
  • 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.

Additional Information

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 these health products both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

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