Drug Safety Alerts

Hepatitis-C Medicines – Mavyret™, Zepatier™, and Vosevi™ MedWatch

08/28/2019

On August 28, 2019, the United States Food and Drug Administration (FDA) issued a notice alerting patients, caregivers, and healthcare professionals that the use of Mavyret^™, Zepatier^™, and Vosevi^™ to treat chronic hepatitis C in patients with moderate to severe liver impairment has resulted in rare cases of worsening liver function or liver failure. All these medicines contain a hepatitis C virus (HCV) protease inhibitor and are not indicated for use in patients with moderate to severe liver impairment. In most patients, symptoms resolved or new onset worsening of liver function improved after stopping the medicine. These medicines have been widely used and are safe and effective in patients with no or mild liver impairment.

In many of the reported cases, liver failure occurred in patients who had signs and symptoms of moderate to severe liver impairment (Child-Pugh B or C) or other serious liver problems and should not have been treated with these medicines. In some cases, patients were reported to have no cirrhosis or compensated cirrhosis with mild liver impairment (Child-Pugh A) despite having evidence of decreased platelets at baseline or an increase in the pressure within the portal vein that carries blood from the digestive organs to the liver. In addition, some cases had other significant pre-existing risk factors such as liver cancer, alcohol abuse, or serious medical illnesses associated with serious liver problems. These factors may have contributed to clinical worsening of liver function or liver failure during treatment with these hepatitis C medicines. In most cases, liver failure or decompensation typically occurred within the first 4 weeks of starting treatment. We will continue to monitor this safety concern and will communicate any new information to the public if it becomes available.

Health care professionals should continue to prescribe Mavyret, Zepatier, and Vosevi as indicated in the prescribing information for patients without liver impairment or with mild liver impairment (Child-Pugh A). Assess severity of liver disease at baseline and closely monitor for signs and symptoms of worsening liver function such as increases in liver enzymes, jaundice, ascites, encephalopathy, and variceal hemorrhage. Assessment of baseline liver disease and close monitoring are especially important in those with pre-existing significant liver problems or risk factors, such as hepatocellular carcinoma or alcohol abuse, which can also contribute to clinical worsening of liver function or liver failure during treatment. Discontinue these medicines in patients who develop signs and symptoms of liver decompensation or as clinically indicated. Mavyret and Zepatier should not be prescribed in patients with any history of prior hepatic decompensation. Vosevi is indicated for patients who have previously failed certain other HCV treatments and is not recommended in patients with any history of hepatic decompensation unless the benefits outweigh the risk of liver injury, liver failure or death.

Mavyret, Zepatier, and Vosevi are FDA-approved to treat chronic hepatitis C in patients without liver impairment or with mild liver impairment (Child-Pugh A). Clinical trials in patients with compensated cirrhosis or mild liver impairment (Child-Pugh A) have shown that these medicines are well tolerated and highly effective. These medicines reduce the amount of HCV in the body by preventing it from multiplying, which over time leads to clearing the virus from the body, or HCV cure, which can prevent or limit liver damage from HCV. HCV is a contagious disease, and without treatment it can lead to serious liver problems, including cirrhosis, liver cancer, and death. When prescribed as indicated, these medicines continue to be safe and effective.

• The FDA recommends the following for healthcare professionals:

• Perform hepatic laboratory testing as clinically indicated or as specified in product labeling.

• Monitor for clinical signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage.

• Discontinue Mavyret, Zepatier, and Vosevi in patients who develop evidence of hepatic decompensation or as clinically indicated.

Encourage patients to read the prescribing information leaflet they receive with their Mavyret, Zepatier, or Vosevi prescriptions because there may be new or important additional information about the medicine.The FDA asks healthcare professionals, patients, and caregivers to report side effects involving Mavyret, Zepatier, or Vosevi to the FDA.

CVS/Caremark^® Response: There have been no recalls issued on this product by the manufacturer. CVS Caremark is not authorized to accept any returns of this product.

For more information about this notice, health care providers may call the U.S. Food and Drug Administration (FDA) consumer inquiry line at 1-888-INFO-FDA (1-888-463-6332) or visit https://www.fda.gov.