VICTRELIS

Boceprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV).

HCV is a single-stranded

RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 7.

Treatment options for chronic Hepatitis

C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Boceprevir.

Boceprevir is an inhibitor of

NS3/4A, a serine protease enzyme, encoded by HCV genotypes and 4 Synthesis.

These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B Label.

The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs 5.

Subtitutions at amino acid positions 155, 156, or are known to confer resistance.

The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself.

Despite this disadvantage Boceprevir is still effective against HCV when paired with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) do not reccomend Boceprevir in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b as first line therapy for Hepatitis C 5.

Boceprevir, Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b are used with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of daily therapy.

SVR and eradication of

HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 6.

Boceprevir is available as a fixed dose product (tradename Victrelis) used for the treatment of chronic Hepatitis C. Approved in May by the FDA, Victrelis is indicated for the treatment of HCV genotype in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b Label.

Victrelis is no longer widely used as interferon-free therapies have been developed.

Boceprevir, when used in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b is indicated for use in the treatment of chronic HCV genotype 1 infection in adults Label.

Boceprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label.

Boceprevir reaches peak plasma concentration 2 hours after administration Label.

Absolute bioavailability has not been determined.

When taken with food exposure increases up to 65%.

In capsule, Boceprevir consists of two diaseromers in a 1:1 ratio.

In plasma this ratio changes to 2:1 favoring the active diastereomer.

The mean apparent volume of distribution for Bocepravir is 772 litres at steady state Label.

Bocepravir is primarily metabolized via the aldo-ketoreductase-mediated pathway producing a diastereomeric mix of metabolites at a 4 fold greater exposure than the parent compound Label.

Boceprevir also undergoes oxidative metabolism via

CYP3A4/5, although to a lesser extent.

Boceprevir is mainly eliminated in the feces (79%) with a small amount eliminated in the urine (9%) Label.

Approximately 8% and 3% is excreted as the parent compound in the feces and urine respectively.

Boceprevir has a mean half-life of elimination of 3.4 hours Label.

Boceprevir has a mean total body clearance of 161 liters per hour Label.

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The most commonly reported adverse reactions in adult subjects were fatigue, anemia, nausea, headache, and dysgeusia when Boceprevir was used in combination with Ribavirin and Peginterferon alfa-2a / Peginterferon alfa-2b Label.