Sofosbuvir is a hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.

Sofosbuvir efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection.

The following points should be considered when initiating treatment with Sofosbuvir:

• Monotherapy of Sofosbuvir is not recommended for treatment of CHC.
• Treatment regimen and duration are dependent on both viral genotype and patient population.
• Treatment response varies based on baseline host and viral factor.

Hepatic viral infections (Hepatitis C)

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase’s GDD active site motif and preventing further replication of HCV genetic material

One 400 mg tablet taken once daily with or without food. Should be used in combination with Ribavirin or in combination with Pegylated Interferon and Ribavirin for the treatment of CHC.

Recommended combination therapy: (HCV Mono-infected and HCV/HIV-1 Co-infected)-

• Genotype 1 or 4: Sofosbuvir + Peginterferon alfa + Ribavirin for 12 weeks
• Genotype 2: Sofosbuvir + Ribavirin for 12 weeks
• Genotype 3: Sofosbuvir + Ribavirin for 24 weeks

Sofosbuvir in combination with Ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are Interferon ineligible

Should be used in combination with Ribavirin for treatment of CHC in patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation whichever occurs first

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease

Reduced therapeutic effect with drugs that are potent P-gp inducers in the intestine (eg rifampicin, St. John’s wort, carbamazepine & phenytoin), modafinil, phenobarb/ oxcarbazepine, rifabutin/ rifapentine. P-gp &/or BCRP inhibitors. May result in serious symptomatic bradycardia when co-administered with amiodarone in combination with another direct acting antiviral.

When Sofosbivur is used in combination with Ribavirin or Peginterferon alfa/ Ribavirin, the contraindications applicable to those agents are applicable to combination therapies. Sofosbuvir combination treatment with Ribavirin or Peginterferon alfa/Ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant, because of the risks for birth defects and fetal death associated with Ribavirin.

The most common adverse events (incidence greater than or equal to 20%, all grades) observed with Sofosbuvir in combination with Ribavirin were fatigue and headache. The most common adverse events observed with Sofosbuvir in combination with Peginterferon alfa and Ribavirin were fatigue, headache, nausea, insomnia, anemia, pruritus, asthenia, rash, decreased appetite, chills, influenza like illness, pyrexia, diarrhea, neutropenia, myalgia, irritability.

Pregnancy Category B: Sofosbuvir There are no adequate and well-controlled studies with Sofosbuvir in pregnant women.

Nursing Mothers: It is not known whether Sofosbuvir and its metabolites are present in human breast milk.

Bradycardia with amiodarone co-administration: Serious symptomatic bradycardia may occur in patients taking amiodarone and Sofosbuvir 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. Co-administration of amiodarone with Sofosbuvir in combination with another DAA is not recommended. In patients without alternative, viable treatment options, cardiac monitoring is recommended.

Pediatric Use: Safety and effectiveness of Sofosbuvir in children less than 18 years of age have not been established.

Geriatric Use: Sofosbuvir was administered to 90 subjects aged 65 and over. The response rates observed for subjects over 65 years of age were similar to that of younger subjects across treatment groups. No dose adjustment of Sofosbuvir is warranted in geriatric patients.

The highest dose of Sofosbuvir is a single dose of Sofosbuvir 1200 mg. No specific antidote is available for overdose treatment. Treatment of overdose with Sofosbuvir consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.