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Boceprevir is the first oral protease inhibitor approved for the treatment of chronic infection with hepatitis C virus (HCV) genotype 1.

The life cycle of HCV begins with the entry of HCV into the host hepatocytes via receptor-mediated endocytosis. This is followed by uncoating of the virus with the release of single-stranded HCV RNA in the cytoplasm. The HCV RNA attaches to the endoplasmic reticulum, where it is translated into a single large polyprotein. This polyprotein is then processed by viral and host proteases into several structural and nonstructural proteins. The structural proteins assemble new viral particles, and the nonstructural proteins participate in viral replication. The major enzymes involved in posttranslational processing are the NS2-3 protease and the NS3/4A protease. Once the viral genome has been translated, viral replication starts. Viral replication is mediated largely by the nonstructural protein NS5B RdRp (RNA polymerase). This is followed by assembly of virions and release from the infected cells.

Boceprevir inhibits the hepatitis C virus NS3/4A serine protease, thereby preventing cleavage of the HCV polyprotein chain and halting viral replication.


  • Boceprevir is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy, including prior null responders, partial responders, and relapsers.
  • Boceprevir must not be used as a monotherapy and should only be used in combination with peginterferon alfa and ribavirin.
  • The efficacy of Boceprevir has not been studied in patients who have previously failed therapy with a treatment regimen that includes Boceprevir or other HCV NS3/4A protease inhibitors.

[edit] DOSAGE

  • 800 mg administered orally three times daily (every 7 to 9 hours) with food (a meal or light snack).
  • Boceprevir must be administered in combination with peginterferon alfa and ribavirin. Initiate therapy with peginterferon alfa and ribavirin for 4 weeks, then add Boceprevir to peginterferon alfa and ribavirin regimen. The duration of treatment is based on viral response, prior response status and presence of cirrhosis.
  • Refer to the prescribing information for peginterferon alfa and ribavirin for specific dosing instructions.


Capsules: 200 mg


  • All contraindications to peginterferon alfa and ribavirin also apply since Boceprevir must be administered with peginterferon alfa and ribavirin.
  • Because ribavirin may cause birth defects and fetal death, boceprevir in combination with peginterferon alfa and ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant.
  • Contraindicated in patients with a history of a hypersensitivity reaction to boceprevir.
  • Coadministration with drugs that are highly dependent on CYP3A4/5 for clearance (e.g., cisapride, lovastatin, midazolam, sildenafil), and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated.
  • Coadministration with potent CYP3A4/5 inducers (e.g.,carbamazepine, phenytoin, and rifampin) where significantly reduced boceprevir plasma concentrations may be associated with reduced efficacy is contraindicated.


Use of Boceprevir with Ribavirin and Peginterferon alfa:

  • Embryofetal Toxicity (Use with Ribavirin and Peginterferon Alfa): Ribavirin may cause birth defects and fetal death; avoid pregnancy in female patients and female partners of male patients. Patients must have a negative pregnancy test prior to therapy; use two or more forms of contraception, and have monthly pregnancy tests.
  • Anemia - The addition of Boceprevir to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations compared with peginterferon alfa and ribavirin alone.
  • Neutropenia - The addition of Boceprevir to peginterferon alfa and ribavirin may result in worsening of neutropenia associated with peginterferon alfa and ribavirin therapy alone.
  • Hypersensitivity – Serious acute hypersensitivity reactions (e.g., urticaria, angioedema) have been observed during combination therapy with Boceprevir, peginterferon alfa and ribavirin.


Boceprevir is a strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5. The potential for drug-drug interactions must be considered prior to and during therapy.


  • Nursing Mothers : It is not known whether Boceprevir is excreted into human breast milk. Levels of boceprevir and/or metabolites in the milk of lactating rats were slightly higher than levels observed in maternal blood. Peak blood concentrations of boceprevir and/or metabolites in nursing pups were less than 1% of those of maternal blood concentrations. Because of the potential for adverse reactions from the drug in nursing infants, a decision must be made whether to discontinue nursing or discontinue treatment with Boceprevir, taking into account the importance of the therapy to the mother.


The most commonly reported adverse reactions (greater than 35% of subjects) in clinical trials in adult subjects receiving the combination of Boceprevir with Peginterferon Alfa and Ribavirin were fatigue, anemia, nausea, headache and dysgeusia.