PRAC: Hep B Reactivation Risk With Direct-Acting Antivirals

Megan Brooks


December 02, 2016

The European Medicines Agency's (EMA's) Pharmacovigilance Risk Assessment Committee (PRAC) has confirmed the risk for hepatitis B virus (HBV) reactivation when direct-acting antiviral drugs are used for treatment of hepatitis C virus (HCV) infection.

The PRAC recommends that, before starting treatment, all patients should be screened for HBV; patients found to be coinfected with HCV and HBV should be monitored and managed according to current clinical guidelines.

The EMA launched a review of direct-acting antivirals in March 2016 following reports of cases of HBV reactivation in patients who had been infected with HBV and HCV and who were treated with direct-acting antivirals for HCV.

"This is thought to be the consequence of the rapid treatment-induced reduction in hepatitis C virus, which is known to suppress the hepatitis B virus, and the lack of activity against hepatitis B virus of direct-acting antivirals," the EMA said on December 2 in announcing the PRAC's conclusions.

Although the frequency of HBV reactivation appears low, the PRAC recommends that a warning be included in the prescribing information for these medicines, the committee said.

The PRAC review covered six direct-acting antivirals marketed in Europe for treatment of chronic HCV infection: daclatasvir (Daklinza, Bristol-Myers Squibb), dasabuvir (Exviera, AbbVie), the combination of sofosbuvir and ledipasvir (Harvoni, Gilead Sciences), simeprevir (Olysio, Janssen), sofosbuvir (Sovaldi, Gilead Sciences), and the combination ombitasvir/paritaprevir/ritonavir (Viekirax, AbbVie).

Since the start of this review, two other direct-acting antivirals, the combination sofosbuvir and velpatasvir (Epclusa, Gilead) and the combination elbasvir and grazoprevir (Zepatier Merck), have been authorized in the European Union.

The US Food and Drug Administration has warned of the possibility of HBV reactivation with direct-acting antiviral drugs used for HCV infection.

Jury Out on Liver Cancer

The PRAC also reviewed the available data on hepatocellular carcinoma in patients treated with direct-acting antivirals and concluded that further studies are needed before firm conclusions can be drawn. The committee will review new data on liver cancer risk with direct-acting antivirals as they become available.

The PRAC recommendation will be forwarded to the Committee for Medicinal Products for Human Use for the agency's final opinion.

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