European Regulators Confirm Hep B Reactivation Risk With Direct Acting Antiviral Hepatitis C Medications

Published on March 7, 2017 by Sandy Liebhard

Regulators in Europe have recommended Hepatitis B screening for all patients being considered for treatment with direct acting antiviral Hepatitis C medications.  According to the European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC), a review has confirmed that these medications may cause Hepatitis B reactivation in co-infected patients.

Direct acting antivirals are a relatively new class of medications approved to treat chronic Hepatitis C. These drugs prevent the replication of the Hep C virus, and in most cases cure the disease. Direct acting antivirals currently approved for use in the U.S. include:

• Daklinza (daclatasvir)
• Epclusa (sofosbuvir and velpatasvir)
• Harvoni (ledipasvir and sofosbuvir)
• Olysio (simeprevir)
• Sovaldi (sofosbuvir)
• Technivie (ombitasvir and paritaprevir and ritonavir)
• Viekira Pak (dasabuvir and ombitasvir and paritaprevir and ritonavir)
• Viekira Pak XR (dasabuvir and ombitasvir and paritaprevir and ritonavir)
• Zepatier (elbasvir and grazoprevir)

PRAC began reviewing direct acting antivirals last March, following reports that co-infected patients treated with the drugs had experienced reactivation of the Hepatitis B virus. The regulator is now recommending that a warning be included in the prescribing information for these medicines.

PRAC also reviewed available data on liver cancer (hepatocellular carcinoma) in patients treated with direct-acting antivirals and concluded that further studies should be carried out before firm conclusions can be drawn.

FDA Orders Black Box Warning for Hepatitis C Drugs

In October, the U.S. Food & Drug Administration (FDA)  mandated that the labels for all direct acting antivirals be modified to include a Black Box Warning regarding the risk of Hep B reactivation in co-infected patients. At the time, the agency said that two dozen cases of Hepatitis B reactivation had been reported among patients taking the medications from November 22, 2013 to July 18, 2016. Two patients died and one required a liver transplant.  The FDA has advised co-infected patients undergoing direct-acting antiviral treatment to contact their doctor immediately if they develop any of the following symptoms:

• Fatigue
• Weakness
• Loss of appetite
• Nausea and vomiting
• Yellow eyes or skin

Direct Acting Antivirals and Liver Failure

In January, the Institute for Safe Medicine Practices (ISMP) reported that its analysis of the FDA’s adverse event database had identified 524 cases of liver failure among patients treated with direct-acting antivirals for the year ending June 30, 2016, including 165 fatalities. An additional 1,058 patients developed severe liver injury.  These cases appeared to be separate from the liver problems associated with Hepatitis B reactivation.

“While it was challenging to separate cases to which complications of Hepatitis C might have contributed, 90% of the cases were submitted by health care professionals, who would be likely to understand the natural progression of the disease,” the ISMP report stated. “Our data show the need for further investigation into the negative consequences of these expensive and important new drugs.”