Boceprevir
Boceprevir Uses, Dosage, Side Effects, Food Interaction and all others data.
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 . 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 . These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B . The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs . 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 . 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 .
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 . Victrelis is no longer widely used as interferon-free therapies have been developed.
| Trade Name | Boceprevir |
| Availability | Discontinued |
| Generic | Boceprevir |
| Boceprevir Other Names | Boceprevir |
| Related Drugs | Epclusa, Mavyret, ribavirin, Harvoni, Sovaldi, Vosevi |
| Type | Oral |
| Formula | C27H45N5O5 |
| Weight | Average: 519.6767 Monoisotopic: 519.342069575 |
| Protein binding | Bocepravir is approximately 75% bound to human plasma proteins following a single dose . |
| Groups | Approved, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Boceprevir is a hepatitis C virus NS3/4A protease inhibitor used in combination with other medications to treat chronic hepatitis C genotype 1 infection. Boceprevir is not indicated as monotherapy.
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 .
Boceprevir is also used to associated treatment for these conditions: Chronic Hepatitis C Genotype 1
How Boceprevir works
Boceprevir is a NS3/4a protease inhibitor used to inhibit viral HCV replication . NS3/4a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NS4A, NS4B, NS5A and NS5B) . Boceprevir covalently but reversibly binds the serine (S139) resiude in the active site via a (α)-ketoamide functional group. This inhibits the proteolytic acitvity of the HCV 1a and 1b encoded enzyme.
Toxicity
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 .
Food Interaction
- Take with or without food. Food decreases drug exposure, but not to a clinically significant extent.
[Moderate] ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir.
When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state.
The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal.
Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.
MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.
Boceprevir Drug Interaction
Major: doxazosin, quetiapine, sildenafilModerate: venlafaxine, nirmatrelvir / ritonavir, orlistatUnknown: amoxicillin / clavulanate, multivitamin, divalproex sodium, interferon alfa-2b, peginterferon alfa-2a, peginterferon alfa-2b, omeprazole, epoetin alfa, finasteride, fluoxetine, montelukast, tiotropium, albuterol, esomeprazole / naproxen
Boceprevir Disease Interaction
Volume of Distribution
The mean apparent volume of distribution for Bocepravir is 772 litres at steady state .
Elimination Route
Boceprevir reaches peak plasma concentration 2 hours after administration . 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.
Half Life
Boceprevir has a mean half-life of elimination of 3.4 hours .
Clearance
Boceprevir has a mean total body clearance of 161 liters per hour .
Elimination Route
Boceprevir is mainly eliminated in the feces (79%) with a small amount eliminated in the urine (9%) . Approximately 8% and 3% is excreted as the parent compound in the feces and urine respectively.
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