Description

Indications Mavixen 100 mg & 40 mg (Glecaprevir & Pibrentasvir) This is a fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor, and is indicated for the treatment of patients with chronic HCV genotype (GT) 1, 2, 3, 4, 5 or 6 infection without cirrhosis and with compensated cirrhosis (Child-Pugh A). This is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both. Pharmacology Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for the proteolytic cleavage of the HCV-encoded polyprotein into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins. These multifunctional proteins, including NS3, are essential for viral replication. The N-terminal of NS3 protein confers serine protease activity, while the C-terminus of NS3 encodes a DExH/D-box RNA helicase which hydrolyzes NTP as an energy source to unwind double-stranded RNA in a 3′ to 5′ direction during replication of viral genomic RNA. NS4A is a cofactor for NS3 that directs the localization of NS3 and modulates its enzymatic activities. Glecaprevir disrupts the intracellular processes of the viral life cycle by inhibiting the NS3/4A protease activity of cleaving downstream junctions of HCV polypeptide and proteolytic processing of mature structural protein. NS5A is a phosphoprotein that plays an essential role in the replication, assembly, and maturation of infectious viral proteins. The basal phosphorylated form of NS5A, which is maintained by the C-terminal serine cluster, is key in ensuring its interaction with the viral capsid protein, or the core protein. By blocking this interaction, pibrentasvir inhibits the assembly of proteins and the production of mature HCV particles. NS5A also interacts with viral and cellular proteins to form the HCV replicate complex, and supports the RNA replication of HCV