Elbasvir/Grazoprevir

Mechanism :

Elbasvir is an inhibitor of HCV NS5A, which is essential for viral replication and virion assembly.
Grazoprevir is an inhibitor of HCV NS3/4A protease, necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication.

Indication :

Chronic hepatitis C genotype 1 or 4 infection

Contraindications :

Moderate or severe hepatic impairment (Child-Pugh class B or C); concurrent use with organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors that are known or expected to significantly increase grazoprevir plasma concentrations and strong inducers of cytochrome P450 3A (CYP3A). Concurrent use of drugs that are contraindicated include, but are not necessarily limited to: Atazanavir, carbamazepine, cyclosporine, darunavir, efavirenz, lopinavir, phenytoin, rifampin, saquinavir, St John’s wort, tipranavir.

Dosing :

Available as 50 mg/100 mg tablet. Safety and efficacy not established in pediatric population.

Adults:

1 tab PO OD. Duration 12 weeks (Genotype 1a, 1b 4, treatment naive). If NSSA polymorphisms to give for 14 weeks in genotype 1a and for 16 weeks in genotype 4.

Adverse Effect :

Fatigue, headache, abdominal pain, diarrhea, irritability, depression, anemia, dyspnea, rash or pruritus, irritability, abdominal pain, depression, arthralgia.

Interaction :

CYP3A4 Inducers: May decrease the serum concentration.
CYP3A4 Inhibitors: May decrease the metabolism of CYP3A4 Substrates.

Hepatic Dose :

Specific guidelines for dosage adjustments in hepatic impairment are not available.