Sofosbuvir - 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.

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 VOSEVI in patients who develop evidence of hepatic decompensation/failure.

Bradycardia with Amiodarone Coadministration: Serious symptomatic bradycardia may occur in patients taking amiodarone with VOSEVI, a sofosbuvir-containing regimen, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease.

Coadministration of amiodarone with VOSEVI is not recommended.

In patients without alternative viable treatment options, cardiac monitoring is recommended. ( 5.3 , 7.3 ) 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 VOSEVI.

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

Initiate appropriate patient management for HBV infection as clinically indicated.

5.2 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including treatment with VOSEVI.

Reported cases occurred in patients with baseline cirrhosis with and without moderate or severe liver impairment (Child-Pugh B or C).

Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In patients with compensated cirrhosis (Child-Pugh A) or evidence of advanced liver disease such as portal hypertension, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage.

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

VOSEVI is not recommended in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation [see Dosage and Administration , Adverse Reactions , Use in Specific Populations , and Clinical Pharmacology ] .

5.3 Serious Symptomatic Bradycardia When Coadministered with Amiodarone Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention have been reported when amiodarone is coadministered with a sofosbuvir-containing regimen.