Background
It is estimated that more than 180 million people worldwide are chronically infected with the hepatitis C virus. Potential severe complications of hepatitis include cirrhosis, liver carcinoma, and liver failure. Of the various genotypes of the virus, genotype 1 in particular responds poorly to current treatment (50%). Standard drugs used include subcutaneous peginterferon alfa and oral ribavirin.
Products
Boceprevir is commercially available in capsule form (Victrelis). It has been approved in many countries since 2011.
Structure and properties
Boceprevir (C27H45N5O5, Mr = 519.7 g/mol) is a peptidomimetic ketoamide. It exists as a mixture of two diastereomers and is a white, amorphous powder that is sparingly soluble in water.
Effects
Boceprevir (ATC J05AE12) has antiviral properties. It inhibits the maturation of the virus and its further replication. The effects are due to inhibition of NS3-serine protease, a viral enzyme that converts the HCV polypeptide into nonstructural proteins. The Active Site of the enzyme consists of a catalytic triad with a serine, a histidine, and an aspartic acid. Boceprevir binds covalently and reversibly to serine 139 via the electrophilic ketoamide group, thereby preventing cleavage of the polypeptide (Figure).
Indications
For the treatment of chronic hepatitis C genotype 1 infection in combination with peginterferon alfa and ribavirin in adult patients with compensated liver disease who have not been pretreated or who have failed to respond to or relapsed on prior therapy.
Dosage
According to the SmPC. Boceprevir is administered three times daily because of its short half-life of 3.4 hours and must be taken with food. Taking it with a meal or snack is mandatory because it greatly increases bioavailability.
Contraindications
Boceprevir is contraindicated in hypersensitivity, autoimmune hepatitis, in combination with CYP3A4/5 substrates, and during pregnancy. For complete precautions and interactions, see the drug label.
Interactions
When combining with other agents, it should be noted in particular that boceprevir is a potent inhibitor of CYP3A4/5 and may result in significant increases in plasma concentrations of the substrates. Boceprevir may provide therapy for coinfection of HIV and HCV by decreasing concentrations of HIV protease inhibitors.
Adverse effects
The most common potential adverse effects include fatigue, anemia, nausea, headache, and taste disturbances. Numerous other side effects are observed.
