27 February 2017

How Safe are the Novel Hepatitis C Drugs?

Lisa A. Banks, PharmD, BCGP VP of Clinical Initiatives

Lisa A. Banks, PharmD, BCGP, VP of Clinical Initiatives

The New York Times published an article on January 24, 2017 entitled “Are New Drugs for Hepatitis C Safe? A Report Raises Concerns.”

It is estimated that 2.2 to 3.3 million persons are chronically infected with Hepatitis C Virus (HCV) in the United States. About 50% are unaware that they are infected because of the virus’ asymptomatic nature. Unknown or untreated infection, over a period of 20 to 25 years, can result in 5% to 20% cirrhosis, which may steadily increase in severity. Among the HCV patients who develop cirrhosis, 1% to 3% per year will develop liver cancer. Early treatments were not as effective, required a longer treatment duration and associated with adverse effects that often resulted in incomplete courses of therapy. The more recent approved treatments, known as direct-acting antivirals (DAAs), are considered novel since have been shown to cure patients affected by HCV with a short treatment duration of 12 weeks and are better tolerated.

HCV treatment remains controversial due to the high-cost (250,000 patients treated in 2015 cost an estimated $19 billion or approximately $125,000 per patient) as well as whether considered to be “curable” (sustained virologic response seen in 89% to 100% of selected patients in controlled clinical trials) and the potentially unknown long-term adverse effects since the drug approval process was expedited (duration of clinical testing reduced from 26 to 12 weeks).

In October 2016, the U.S. Food and Drug Administration (FDA) requested black box warnings be added to the DAAs about the risk of Hepatitis B Virus (HBV) re-activation and monitoring requirements, following the identification of 24 known cases.

Most recently, in January 2017, the Institute for Safe Medication Practices (ISMP) reported on the emerging risks of the novel HCV treatments for triggering liver failure. For the 12 months ending June 30, 2016, ISMP identified 524 cases of liver failure associated with all the approved DAAs as either primary or secondary suspect drugs (with the exception of sofosbuvir-velpatasvir since was not approved until the end of 2Q2016), often in combination with each other or with ribavirin, and an additional 1058 cases of severe liver injury. Of the 524 liver failure cases, 165 cases resulted in mortality. Furthermore, 761 cases were identified as antiviral failure.

These findings are inconclusive since a causal relationship has not been proven and should be cautiously interpreted. Patients with underlying HCV infection are at risk for clinical complications, including the progression of advanced liver disease. This analysis is limited since did not include medical histories, including genotype and whether or not cirrhosis was present to what severity classification.

The benefit versus risk of HCV treatment needs to be considered and be individualized for the patient. CareKinesis has developed a HCV Therapy Protocol, as well as accompanying expectations and monitoring forms, with the intention to provide guidance to PACE organizations with HCV infected patients in determining treatment benefit versus risk (candidate), treatment options, monitoring and special considerations. The document is reflective of the American Association for the Study of Liver Diseases – Infectious Diseases Society of America (AASLD-IDSA) Practice Guidelines. An electronic version is available in the Partner Resources section of the EireneRx® platform.


  • Grady, Denise. Are New Drugs for Hepatitis C Safe? A Report Raises Concerns. The New York Times. January 24, 2017. https://nyti.ms/2kpd1pG
  • AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. 2016. www.hcvguidelines.org.
  • FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C. October 4, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm
  • ISMP QuarterWatch: Monitoring FDA MedWatch Reports. January 25, 2017 – new data from 2016 Q2. http://www.ismp.org/QuarterWatch/pdfs/2016Q2.pdf