Earlier this week, the U.S. Food and Drug Administration (FDA) warned about serious risks for patients infected with the hepatitis B virus (HBV) and who are being treated with certain direct-acting antiviral (DAA) drugs for the hepatitis C virus (HCV). DAA medications prevent hepatitis C from multiplying, and in most cases, they cure HCV (a list of DAAs is available through this FDA link).
The FDA’s warning was triggered by reports of hepatitis B reactivation in patients who have been infected with both hepatitis B and C viruses and were under treatment with DAA drugs. Hepatitis B reactivation refers to a return of active infection in a patient whose hepatitis B infection had been inactive.
Twenty-four cases of HBV reactivation in HCV/HBV co-infected patients treated with DAA drugs were reported to the FDA and published in medical articles over 31 months, from Nov. 22, 2013 to July 18, 2016.
Of the cases reported, HBV reactivation usually occurred within four to eight weeks of treatment and caused two deaths. One patient needed a liver transplant. The FDA, however, warns that these are the cases they are aware of, but additional cases are likely to have occurred.
As a result, the FDA is now requiring a boxed warning to be added to nine DAA drugs. These include Harvoni and Sovaldi (Gilead), Viekra Pak (Abbvie), and Daklinza (Bristol-Myers Squibb). This warning will also be included in the patient information leaflet or medication guides for these drugs.
The FDA noted that HBV reactivation was not reported as an adverse reaction in the DAA’s clinical studies that led to approval of these drugs. This was mainly due to the fact that HBV co-infection was an exclusion criteria in these trials.
Now, the FDA is asking healthcare professionals and patients to report any adverse events related to DAA medications to its MedWatch Safety Information and Adverse Event Reporting Program.
The FDA recommends that all patients should be screened for prior or current HBV infection before initiating DAA therapy, and also advises health professionals to monitor patients using blood tests for HBV flare-ups or reactivation during treatment, as well as at post-treatment follow-up.
In March, the European Medicines Agency (EMA) started a review of DAA medications. Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) also said that a review of these medications in underway in the country.
Patients should tell their doctors about a history of hepatitis B infection or other liver problems before being treated for hepatitis C, and should not stop taking their DAA treatment without talking to their doctors first.