Elbasvir and grazoprevir - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment.

Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up.

Initiate appropriate patient management for HBV infection as clinically indicated.

ALT Elevations: Perform hepatic laboratory testing prior to therapy, at treatment week 8, and as clinically indicated.

For patients receiving 16 weeks of therapy, perform additional hepatic laboratory testing at treatment week 12.

For ALT elevations on ZEPATIER, follow recommendations in full prescribing information.

Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease: Hepatic decompensation/failure, including fatal outcomes, have been reported mostly in patients with cirrhosis and baseline moderate or severe liver impairment (Child-Pugh B or C) treated with HCV NS3/4A protease inhibitor-containing regimens.

Monitor for clinical and laboratory evidence of hepatic decompensation.

Discontinue ZEPATIER in patients who develop evidence of hepatic decompensation/failure.

Risk Associated with Ribavirin Combination Treatment: If ZEPATIER is administered with ribavirin, the warnings and precautions for ribavirin also apply.

5.1 Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals, and who were not receiving HBV antiviral therapy.

Some cases have resulted in fulminant hepatitis, hepatic failure and death.

Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive).

HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients.

HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level.

In patients with resolved HBV infection reappearance of HBsAg can occur.

Reactivation of HBV replication may be accompanied by hepatitis, i.e., increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur.

Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with ZEPATIER.

In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with ZEPATIER and during post-treatment follow-up.

Initiate appropriate patient management for HBV infection as clinically indicated.

5.2 Increased Risk of ALT Elevations During clinical trials with ZEPATIER with or without ribavirin, 1% of subjects experienced elevations of ALT from normal levels to greater than 5 times the upper limit of normal (ULN), generally at or after treatment week 8.

ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy.

Higher rates of late ALT elevations occurred in the following subpopulations: female sex (2% [10/608]), Asian race (2% [4/164]), and age 65 years or older (2% [3/177]) [see Adverse Reactions ] .

Hepatic laboratory testing should be performed prior to therapy, at treatment week 8, and as clinically indicated.

For patients receiving 16 weeks of therapy, additional hepatic laboratory testing should be performed at treatment week 12.