Trade name Sovaldi.

A direct acting nucleotide polymerase inhibitor that is an oral agent or the treatment of chronic HCV infection.

Sofosbuvir in combination with ribavirin for treatment of patients with genotype 2 and 3 HCV, and in combination with pegylated interferon and ribavirin, for patients with genotype 1 and 4 infection.

Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor.

Not recommended as monotherapy.

Data for genotypes 2 and 3, the combination of sofosbuvir and ribavirin was both efficacious and safe and would is the first all-oral, interferon-free treatment for HCV.

Sofosbuvir appears to offer better efficacy in patients with genotype 2 than in those with genotype 3.

Among those with HCV genotypes 1 and 4, sofosbuvir plus pegylated interferon and ribavirin would offer increased efficacy and shorter treatment than currently approved regimens.

Nucleotide analogues are phosphorylated within hosts hepatocytes to active nucleoside triphosphate, which competes with the natural nucleotides, terminating RNA replication in the nascent viral genome.

Virologic breakthrough not observed with this drug.

Inhibits all HCV genotypes.

Active triphosphate nucleotide analogs target the active site of the HCV-specific NS5B polymerase, acting as a non-obligate chain terminator, an effect independent of the viral genotype.

Monotherapy at 400 mg for seven days results in a profound reduction in the level of HCV RNA in patients with HCV genotype 1 infection (Lawitz E et al).

12 weeks of treatment with this agent in combination with pegylated interferon and ribavirin results in decreases in the level of HCV RNA leading to sustain viral response at 24 weeks in 92% of patients with HCV genotype two or three infection(Lalezari J et al).

The same regimen used as above, followed by 12 weeks of peg interferon and ribavirin resulted in a sustained viral response 24 weeks after treatment in 89% of patients with HCV genotype 1 infection (Lawitz E et al).

In a randomized study of patients with hepatitis C receiving Sofosbuvir plus ribavirin a sustained virologic response was seen in all previously untreated patients with HCV genotype 2 or 3 infection and in the majority of previously untreated patients with HCV genotype 1 infection (Gane EJ et al).

Patients with genotype 4 or 6 have high rates of sustained virologic response with a 24 week regimen of sofosbuvir plus PEG interferon- ribavirin.

Sofosbuvir combined with Peginterferon-riboflavin in predominately 1 or 4 HCV infection hadbsustained virologic response of 90% at 12 weeks (Lawitz E et al).

In a non-inferiority trial patients with genotype two or three HCV infection randomly assigned to receive sofosbuvir-ribavirin for 12 weeks or peginterferon plus ribavirin for 24 weeks: They had nearly identical rates of response at 67% with less frequent adverse event in the sofosbuvir group (Lawitz E ey al).

Recommended treatment for genotypes 1 and 4 is 12 weeks of pegylated interferon , ribavirin and Sofosbuvir.

Recommended treatment for Genotype 2 is 12 weeks of ribavirin and Sofosbuvir.

Recommended treatment for Genotype 3 is 24 weeks of ribavirin plus Sofosbuvir.

In patients with chronic hepatitis C with genotype 1 infection ineligible to receive interferon regimen may be treated with a combination of ribavirin plus Sofosbuvir for 24 weeks.

Almost all patients with untreated hepatitis C and all patients with genotype one infection who previously failed treatment with Telaprevir or boceprevir were cured with oral combination of Daclatasvir plus sofosbuvir in 211 patients (Sulkowski MS et al).

Should not be used with rifampin or St. John’s wort as they may significantly decrease plasma concentrations of sofosbuvir and reduce its therapeutic effect.

Concomitant therapy is not recommended with Carbamazine, oxcarbamzine, phenobarbital, phenytoin, Tipranavir/ritonavir as the combination will decrease the concentration of the agent.

Most common adverse reactions for sofosbuvir and peginterferon alpha combinations are fatigue, headache, nausea, insomnia, and anemia.

In combination with ribavirin the most common side effects are fatigue and headache.

Recommended for patients with hepatocellular awaiting transplantation; in combination with ribavirin for up to 48 weeks or up to time of transplantation, to prevent post transplant HCV reinfection.

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