Information about Boceprevir
Boceprevir is an oral, direct acting hepatitis C virus (HCV) protease inhibitor that is used in combination with other antiviral agents in the treatment of chronic hepatitis C, genotype 1.
Liver safety of Boceprevir
Boceprevir has not been linked to instances of acute liver injury during therapy but, when combined with peginterferon and ribavirin, has been associated with cases of hepatic decompensation in patients with preexisting cirrhosis.
Mechanism of action of Boceprevir
The hepatitis C virus is a small RNA virus that is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in the United States as well as worldwide. Various approaches to antiviral therapy of chronic hepatitis C have been developed, starting in the 1980s with interferon alfa which was replaced in the 1990s by long acting forms of interferon (peginterferon) to which was added the oral nucleoside analogue, ribavirin. Between 2010 and 2015, several potent oral, direct acting anti-HCV agents were developed and combinations of these found to have marked activity against the virus, allowing for highly effective therapy without use of interferon with treatment courses of 12 to 24 weeks only. These direct acting agents included HCV protease (NS3/4) inhibitors, structural replication complex (NS5A) inhibitors and the HCV RNA polymerase (NS5B) inhibitors. The HCV protease inhibitors block the activity of the viral encoded protease that is essential in the posttranslational modification of the viral polypeptide, cleaving it into a series of structural and nonstructural (NS: enzyme) regions. The HCV proteases that have been developed are polypeptide-like molecules, modified amino acids that that resemble the specific amino acid sequence that the protease cleaves and act as competitive inhibitors of the protease enzyme. At least four HCV protease inhibitors (all having the suffix: -previrs) have been approved for use in the United States: boceprevir , telaprevir , simeprevir , and paritaprevir .
Mechanism of action of Boceprevir
Boceprevir (boe se' pre vir) was one of the first direct acting agents developed as therapy of hepatitis C. Like other HCV protease inhibitors, boceprevir blocks the activity of the viral encoded protease (HCV nonstructural [NS] region 3/4) that is essential in the posttranslational modification of the viral polypeptide, that is cleaved into a series of structural and nonstructural (enzyme) regions. When used by itself, it results in rapid inhibition of HCV RNA levels, but resistance develops rapidly in a high proportion of patients. When combined with peginterferon and ribavirin, it was shown to provide a sustained inhibition of HCV RNA with a low rate of antiviral resistance. Triple therapy with boceprevir, peginterferon and ribavirin, when given for 44 to 48 weeks, increased the sustained virological response (SVR) rate from 40% to 50% (peginterferon and ribavirin alone) to 65% to 75% in patients with genotype 1.
FDA approval information for Boceprevir
Boceprevir was approved for use in the United States in 2012 for patients with chronic hepatitis C, genotype 1, in combination with peginterferon and ribavirin. Since that time, boceprevir has been largely replaced by more potent and better tolerated oral antiviral agents that can be given without peginterferon, but it is still available under the brand name Victrelis as capsules of 200 mg. The recommended dose is 800 mg three times daily.
Side effects of Boceprevir
The side effects of boceprevir are difficult to separate from those of the coadministered peginterferon and ribavirin, but the triple therapy is associated with a higher rate of many side effects, including anemia, fatigue, headache, nausea, itching, rash and neutropenia.
The following are drugs for Hepatitis C:
HCV NS5A Inhibitors
HCV NS5B (Polymerase) Inhibitors
HCV Protease Inhibitors
- Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir