Sofosbuvir

DEA Class; Rx

Common Brand Names; Sovaldi

• Hepatitis B/Hepatitis C Agents; 
• HCV Polymerase Inhibitors

Hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor
For chronic hepatitis C infection, genotypes 1, 2, 3, and 4, in adult patients and genotypes 2 and 3 in pediatric patients 3 years and older, including those with hepatocellular carcinoma awaiting liver transplant, and HCV/HIV coinfection
Black Box Warning regarding reactivation of hepatitis B virus (HBV) infection in HCV/HBV coinfected patients; screen all patients for HBV before initiating treatment.

Contraindications applicable to combination therapy

Combination with ribavirin

• Hypersensitivity
• Pregnancy or planning pregnancy, including men whose female partners are pregnant/planning to get pregnant
• CrCl <50 mL/min
• Pancreatitis
• Hemoglobinopathies (eg, thalassemia major, sickle cell anemia)
• Coadministration with didanosine
• Autoimmune hepatitis, decompensated liver disease (Child-Pugh class B, C)
• Use in neonates, infants (contains benzyl alcohol)

Combination with peg-interferon alfa

• Autoimmune hepatitis, decompensated liver disease (Child-Pugh class B, C)
• Use in neonates, infants (contains benzyl alcohol)

Sofosbuvir plus ribavarin (12 weeks)

• Fatigue (38%)

• Headache (24%)

• Nausea (22%)

• Insomnia (15%)

• Pruritus (11%)

Sofosbuvir plus ribavarin (24 weeks)

• Fatigue (30%)

• Headache (30%)

• Nausea (13%)

• Insomnia (16%)

• Pruritus (27%)

• Asthenia (21%)

• Diarrhea (12%)

Sofosbuvir plus ribavarin plus peg-interferon (12 weeks)

• Fatigue (59%)

• Headache (36%)

• Nausea (34%)

• Insomnia (25%)

• Pruritus (17%)

• Anemia (21%)

• Rash (18%)

• Decreased appetite (18%)

• Chills (17%)

• Influenza-like illness (16%)

• Pyrexia (18%)

• Diarrhea (12%)

• Neutropenia (17%)

• Myalgia (14%)

• Irritability (13%)

Sofosbuvir plus ribavarin plus peg-interferon (24 weeks)

• Fatigue (55%)

• Headache (44%)

• Nausea (29%)

• Insomnia (29%)

• Pruritus (17%)

• Anemia (12%)

• Rash (18%)

• Decreased appetite (18%)

• Chills (18%)

• Influenza-like illness (18%)

• Pyrexia (14%)

• Diarrhea (17%)

• Neutropenia (12%)

• Myalgia (16%)

• Irritability (16%)

Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs, and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)

Drugs that are potent P-gp inducers in the intestine (eg, rifampin, St. John’s wort) may significantly decrease sofosbuvir plasma concentrations

Serious symptomatic bradycardia may occur in coadministration with amiodarone in combination with another direct acting antiviral (DAA), particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease; coadministration is not recommended, if no alternative exists, inpatient cardiac monitoring is recommended for the first 48 hr and then daily home monitoring for at least the first 2 weeks

Must NOT be used as monotherapy

Use with other drugs containing sofosbuvir not recommended

If therapy administered with ribavirin or peginterferon alfa and ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partners are pregnant;

Not known whether sofosbuvir or metabolites are present in human breast milk, affect human milk production or have effects on breastfed infant; the predominant circulating metabolite of sofosbuvir (GS-331007) was the primary component observed in the milk of lactating rats, without effect on nursing pups