Elbasvir/grazoprevir

Elbasvir/grazoprevir is a fixed-dose combination antiviral drug used in the treatment of chronic hepatitis C (HCV) infection. It combines two direct-acting antivirals: elbasvir, which is an NS5A inhibitor, and grazoprevir, a protease inhibitor. This combination is specifically indicated for the treatment of chronic hepatitis C genotypes 1 and 4. It is marketed under the brand name Zepatier by Merck & Co.

Medical Uses

Elbasvir/grazoprevir is used for the treatment of adult patients with chronic hepatitis C virus (HCV) genotypes 1 or 4 infection, including those with compensated cirrhosis (Child-Pugh A). The treatment duration varies depending on the patient's viral genotype, prior treatment history, and presence of cirrhosis, typically ranging from 12 to 16 weeks.

Mechanism of Action

Elbasvir acts as an NS5A inhibitor, interfering with the viral RNA replication and virion assembly of hepatitis C virus, while grazoprevir inhibits the HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms, thus preventing viral replication. The combination of these two mechanisms of action provides a potent antiviral effect against HCV.

Adverse Effects

Common adverse effects of elbasvir/grazoprevir include fatigue, headache, and nausea. Less frequently, elevated liver enzymes and bilirubin levels may occur. It is important to monitor liver function tests before and during treatment. The use of elbasvir/grazoprevir with certain other medications may increase the risk of adverse effects and is contraindicated with drugs that strongly induce or inhibit CYP3A4, as these can significantly alter elbasvir and grazoprevir plasma concentrations.

Drug Interactions

Elbasvir/grazoprevir is metabolized primarily by the CYP3A4 enzyme. Concomitant use with strong inducers of CYP3A4 can lead to reduced efficacy of elbasvir/grazoprevir, while strong inhibitors can increase the risk of adverse effects. Therefore, careful consideration and adjustment of concomitant medications are necessary during treatment with elbasvir/grazoprevir.

Pharmacokinetics

The pharmacokinetic properties of elbasvir and grazoprevir are affected by their metabolism through the CYP3A4 pathway. Both components have a high oral bioavailability and are subject to hepatic metabolism. They are primarily excreted in the feces.

Approval and Regulation

Elbasvir/grazoprevir was approved by the Food and Drug Administration (FDA) in January 2016 for the treatment of chronic hepatitis C genotypes 1 and 4. The approval was based on a series of clinical trials demonstrating high cure rates (sustained virologic response) in patients with HCV genotypes 1 and 4, including those with compensated cirrhosis and those with HIV co-infection.

Conclusion

Elbasvir/grazoprevir represents a significant advancement in the treatment of chronic hepatitis C, offering a highly effective and well-tolerated option for patients with genotypes 1 and 4. Its approval has expanded the arsenal of direct-acting antivirals, contributing to the goal of eradicating HCV infection.