VICTRELIS CAPSULES

Indications

• Chronic hepatitis C virus infection
• HCV genotype 1 infection

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Boceprevir selectively and covalently binds to the serine (S139) residue in the active site of the HCV NS3/4A protease via an alpha-ketoamide functional group. This binding inhibits the proteolytic activity of the enzyme, preventing the cleavage of the HCV polyprotein into functional proteins (NS4A, NS4B, NS5A, NS5B), thereby inhibiting HCV replication within host cells.

Pharmacodynamics

Boceprevir is classified as a direct-acting antiviral (DAA) that effectively prevents viral replication specifically in HCV genotype 1. Its inhibition of the NS3/4A protease is critical for reducing the viral load in patients infected with HCV.

Pharmacokinetics

Boceprevir exhibits a complex pharmacokinetic profile, with absorption, distribution, metabolism, and excretion influenced by various factors. It is primarily metabolized by the liver, and its elimination half-life is approximately 3 to 4 hours. The drug's pharmacokinetics may be affected by food intake and other medications, necessitating careful consideration during therapy.

Contra-indications

• Hypersensitivity to boceprevir or any of its components
• Severe hepatic impairment (Child-Pugh class C)

Adverse effects

• Fatigue
• Nausea
• Headache
• Anemia
• Rash
• Dysgeusia (altered taste)

Interactions

• Strong CYP3A4 inducers (e.g., rifampicin, St. John's Wort) may decrease boceprevir levels
• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase boceprevir levels
• Boceprevir may increase the plasma concentrations of certain drugs metabolized by CYP3A4

Precautions

• Monitor liver function tests during treatment
• Use with caution in patients with a history of liver disease
• Monitor for signs of anemia and adjust treatment as necessary
• Consider potential drug interactions when prescribing

Pregnancy

Boceprevir is not recommended during pregnancy due to potential risks to the fetus. Adequate contraception should be used during treatment and for 6 months after completion.

Breast-feeding

It is not known if boceprevir is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Capsules: 200 mg

Mechanism of action

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. Boceprevir is a selective hepatitis C virus (HCV) nonstructural (NS) 3/4A protease inhibitor. The drug is a direct-acting antiviral agent with activity against HCV. Boceprevir contains an alpha-ketoamide functional group that selectively, covalently, and reversibly binds the active serine site of HCV NS3 protease. By blocking proteolytic cleavage of NS4A, NS4B, NS5A, and NS5B from the HCV-encoded polyprotein, the drug inhibits HCV replication in host cells. Boceprevir has in vitro activity against HCV genotypes 1a and 1b, but is less active against genotypes 2, 2a, and 3a. Boceprevir is an inhibitor of the HCV NS3/4A protease that is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins. Boceprevir covalently, yet reversibly, binds to the NS3 protease active site serine (S139) through an (alpha)-ketoamide functional group to inhibit viral replication in HCV-infected host cells. In a biochemical assay, boceprevir inhibited the activity of recombinant HCV genotype 1a and 1b NS3/4A protease enzymes, with Ki values of 14 nM for each subtype. ... Boceprevir is a ketoamide protease inhibitor that binds reversibly to the HCV nonstructural NS3 protease active site inhibiting intracellular viral replication. Phase III clinical studies have demonstrated that, in combination with the current standard of care, boceprevir significantly increases the a sustained virological response rate in both treatment-naive and previously treated patients with genotype 1 CHC. ...

Pharmacodynamics

Boceprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1.