FDA Issues Warning, AbbVie Explains Label Changes for HCV Drugs

The FDA released a statement warning of serious liver injury caused by the hepatitis C virus treatments ombitasvir/paritaprevir/ritonavir plus dasabuvir and ombitasvir/paritaprevir/ritonavir in patients with pre-existing advanced liver disease. In response, AbbVie spoke to HCV Next about the changes they have implemented to the drug labels to reflect this risk.

“Our review of adverse events reported to the FDA Adverse Event Reporting System (FAERS) database and to the manufacturer of these medicines … identified cases of hepatic decompensation and liver failure in patients with underlying liver cirrhosis who were taking these medicines,” the agency wrote in the statement. “These serious outcomes were reported mostly in patients taking Viekira Pak who had evidence of advanced cirrhosis even before starting treatment.”

In communication with HCV Next, an FDA spokesperson said: “Of the 26 assessable cases in which causality to components of Viekira Pak or Technivie was attributed to be possible or probable, 10 patients experienced hepatic failure resulting in transplantation or death, and 16 patients experienced various degrees of liver dysfunction.”

However, some of these cases occurred in patients for whom the drugs were contraindicated or not recommended. Viekira Pak is indicated for genotype 1 HCV infection while Technivie was more recently indicated for genotype 4.

“The FDA emphasizes that Viekira Pak and Technivie are contraindicated in moderate and severe hepatic impairment,” the FDA spokesperson told HCV Next. “Technivie is not indicated for use in patients with cirrhosis. Some of the postmarketing cases of hepatic failure occurred in patients for whom Viekira Pak and Technivie are contraindicated or not recommended. Some cases provided insufficient data to definitively assess baseline liver status.”

The FDA required AbbVie, the manufacturer of the treatments, to add information about these safety risk to the drug labels.

“Patients taking these medicines should 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 liver injury,” the FDA wrote in the statement. “Health care professionals should closely monitor for signs and symptoms of worsening liver disease, such as ascites, hepatic encephalopathy, variceal hemorrhage, and/or increases in direct bilirubin in the blood.”

AbbVie Addresses Changes

“The label update contraindicates the use of Viekira Pak and Technivie in patients with Child-Pugh B cirrhosis, also known as decompensated cirrhosis,” Barry Bernstein, MD, vice president, infectious disease development, AbbVie, told HCV Next. “The label updates … were based on postmarketing reports we have received this year on patients mostly with advanced cirrhosis who had decompensation which was complicated by the need for a liver transplant and in some patients, resulted in a fatal outcome.

“We have been monitoring these reports and analyzing with the FDA and agreed to update our label to reflect these reports.”

Bernstein explained that the reports are postmarketing reports that are spontaneously received and not from a clinical trial.

“[This makes it] difficult to estimate or establish a causal relationship to the drugs,” Bernstein said. “However, safety is certainly a primary concern for patients receiving any of our medications including Viekira Pak and in consultation and discussion with the FDA, we decided to update the labels to reflect reports.”

The FDA also told HCV Next that these types of cases can be difficult to evaluate. “The postmarketing cases of hepatic decompensation and liver failure are difficult to interpret because they occurred mostly in patients with underlying advanced chronic liver disease,” the spokesperson said. “However, temporal association from starting Viekira Pak or Technivie and resolution of symptoms in some patients after the medicine was stopped suggest a potential causal association.”

According to Bernstein, the original label for Viekira Pak indicated that its use was not recommended for patients with Child-Pugh B cirrhosis, but the update includes the contraindication for this subset of patients, which represents about 3% to 5% of all patients with HCV in the U.S. The indication for use in patients who have Child-Pugh A cirrhosis, or compensated cirrhosis, and those without cirrhosis remains unchanged, according to Bernstein:

“We do monitor all reports received of adverse events and will continue to monitor additional reports of similar adverse events in the future,” Bernstein said.

AbbVie has reached out to clinicians and health care providers to indicate the changes in the label, according to Bernstein.

“We take patient safety and responsibility very seriously and have communicated through multiple different channels.”

The new updates are reflected on both the Viekira Pak and Technivie labels and are exactly the same. However, Technivie was never indicated for use in patients with any level of cirrhosis, according to Bernstein.

“The labels were slightly different in that regard, but both reflect label changes now,” Bernstein said.

Despite some amount of patients experiencing injury or fatal outcomes, Bernstein said AbbVie is “very confident” with the drugs and their treatment for HCV.

“We remain very confident in the safety profile and we feel Viekira Pak and Technivie are very important therapeutic options for patients with hepatitis C and will remain so,” he said.

The updated labels for Viekira Pak and Technivie can be viewed on the FDA website. – by Melinda Stevens

Disclosure: Bernstein is employed by AbbVie.