October 2016 FDA Drug Safety Communication Warns About These Relatively New Drugs Which Are Increasingly Popular For Treating Chronic Hepatitis C
In April 2016 we posted this article, "European Drug Regulators Consider Whether Harvoni, Sovaldi, And Other New "Hep-C" Drugs May Cause Liver Cancer Return, Hepatitis B Reactivation".
Today, about six months later, the FDA indicated their concern for these relatively new chronic hepatitis C treatment drugs -- including Harvoni, Sovaldi, and Viekira Pak -- by issuing a Drug Safety Communication which started with this statement:
The FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death. HBV reactivation usually occurred within 4-8 weeks.
As a result, FDA is requiring a Boxed Warning, our most prominent warning, about the risk of HBV reactivation to be added to the drug labels of these DAAs directing health care professionals to screen and monitor for HBV in all patients receiving DAA treatment. This warning will also be included in the patient information leaflet or Medication Guides for these medicines.
As background, direct-acting antivirals (DAAs) are a class of prescription medicines that are FDA-approved to treat adults with hepatitis C virus (HCV) infection. These medicines are available as single-ingredient products and also in combination with other HCV medicines.
Here is a list of direct-acting antivirals currently available in the US:
Daklinza (daclatasvir) -- Bristol-Myers Squibb
Epclusa (sofosbuvir and velpatasvir) -- Gilead Sciences
Harvoni (ledipasvir and sofosbuvir) -- Gilead Sciences
Olysio (simeprevir) -- Janssen
Sovaldi (sofosbuvir) -- Gilead Sciences
Technivie (ombitasvir and paritaprevir and ritonavir) -- Abbvie
Viekira Pak (dasabuvir and ombitasvir and paritaprevir and ritonavir) -- Abbvie
Viekira Pak XR (dasabuvir and ombitasvir and paritaprevir and ritonavir) -- Abbvie
Zepatier (elbasvir and grazoprevir) -- Merck Sharp Dohme
Strictly Confidential, No Obligation.
Returning to the "FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C", which was issued on October 4, 2016:
FDA identified 24 cases of HBV reactivation reported to FDA and from the published literature in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22, 2013 to July 18, 2016. This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware. Of the cases reported, two patients died and one required a liver transplant. HBV reactivation was not reported as an adverse event in the clinical trials submitted for the DAA approvals because patients with HBV co-infection were excluded from the trials.
And from that same FDA Drug Safety Communication about Harvoni, Sovaldi, and Viekira Pak, as well as other direct-acting antiviral (DAA) medicines for the hepatitis C virus, we get this more precise medical information:
- Hepatitis B virus (HBV) reactivation has occurred in patients co-infected with hepatitis C virus (HCV) while undergoing treatment with DAAs for HCV infection. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. This risk has been observed with DAAs used without interferon to treat HCV infection.
- HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of hepatitis B surface antigen (HBsAg) in a person who was previously HBsAg negative and hepatitis B core antibody (anti-HBc) positive. Reactivation of HBV replication is often followed by hepatitis, i.e., an increase in transaminase levels and, in severe cases, an increase in bilirubin levels, hepatic failure, and death.
- The mechanism through which HBV reactivation occurs is currently unknown.
- Cases of HBV reactivation have been reported in HCV patients treated with DAAs who are hepatitis B surface antigen (HBsAg) positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive), and were not receiving HBV antiviral treatment.
Finally, the FDA has advised patients using any of these DAA medicines for treat chronic hepatitis C virus (HCV) infection to contact their health care professional immediately if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of serious liver problems.
Of course, we will continue to monitor the safety profiles of Harvoni, Sovaldi, and Viekira Pak, as well as the several other direct-acting antiviral (DAA) medicines, and report further significant developments.
DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects (All website content by attorney Tom Lamb)
Drug Injury Case Evaluation - Free. Confidential. No Obligation. (Case review done by attorney Tom Lamb)