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 1 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 ^{[FDA 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 168 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 2011 by the FDA, Victrelis is indicated for the treatment of HCV genotype 1 in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b ^{[FDA Label]}. Victrelis is no longer widely used as interferon-free therapies have been developed.

• Acids, Acyclic
• Amino Acids
• Amino Acids, Cyclic
• Amino Acids, Peptides, and Proteins
• Antiinfectives for Systemic Use
• Antivirals for Systemic Use
• Combined Inhibitors of CYP3A4 and P-glycoprotein
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strong)
• Cytochrome P-450 CYP3A4 Substrates
• Direct Acting Antivirals
• Imines
• Imino Acids
• NS3/4A Protease Inhibitors
• P-glycoprotein/ABCB1 Inhibitors
• P-glycoprotein/ABCB1 Substrates
• Protease Inhibitors

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 ^{[FDA Label]}.

• Genotype 1 chronic hepatitis C infection

Boceprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 ^{[FDA Label]}.

Boceprevir reaches peak plasma concentration 2 hours after administration ^{[FDA 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 ^{[FDA Label]}.

Bocepravir is approximately 75% bound to human plasma proteins following a single dose ^{[FDA Label]}.

Boceprevir is mainly eliminated in the feces (79%) with a small amount eliminated in the urine (9%) ^{[FDA 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 ^{[FDA Label]}.

Boceprevir has a mean total body clearance of 161 liters per hour ^{[FDA Label]}.

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 ^{[FDA Label]}.

• Hepatitis C Virus

• Food increases the exposure of boceprevir by up to 65%. However, bioavailability is not affected and thus can be taken without regards to meals.

1. Kiser JJ, Flexner C: Direct-acting antiviral agents for hepatitis C virus infection. Annu Rev Pharmacol Toxicol. 2013;53:427-49. doi: 10.1146/annurev-pharmtox-011112-140254. Epub 2012 Nov 5. [PubMed:23140245 ]
2. Treitel M, Marbury T, Preston RA, Triantafyllou I, Feely W, O'Mara E, Kasserra C, Gupta S, Hughes EA: Single-dose pharmacokinetics of boceprevir in subjects with impaired hepatic or renal function. Clin Pharmacokinet. 2012 Sep 1;51(9):619-28. doi: 10.2165/11633440-000000000-00000. [PubMed:22799589 ]
3. Wilby KJ, Partovi N, Ford JA, Greanya E, Yoshida EM: Review of boceprevir and telaprevir for the treatment of chronic hepatitis C. Can J Gastroenterol. 2012 Apr;26(4):205-10. [PubMed:22506260 ]
4. Malcolm BA, Liu R, Lahser F, Agrawal S, Belanger B, Butkiewicz N, Chase R, Gheyas F, Hart A, Hesk D, Ingravallo P, Jiang C, Kong R, Lu J, Pichardo J, Prongay A, Skelton A, Tong X, Venkatraman S, Xia E, Girijavallabhan V, Njoroge FG: SCH 503034, a mechanism-based inhibitor of hepatitis C virus NS3 protease, suppresses polyprotein maturation and enhances the antiviral activity of alpha interferon in replicon cells. Antimicrob Agents Chemother. 2006 Mar;50(3):1013-20. [PubMed:16495264 ]
5. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432 ]
6. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348 ]
7. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]

• J05AE — Protease inhibitors
• J05A — DIRECT ACTING ANTIVIRALS
• J05 — ANTIVIRALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

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