Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

Abstract

Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.

Adverse drug reactions during hepatitis C treatment with direct-acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting syste

“…The most commonly detected preventable criterion was labelled drug‐drug interaction of coadministered drugs with DAA. This finding is in‐line with previous results from other sources that emphasized the critical role of drug‐drug interactions with the pharmacological use of this drug class . Direct antiviral agents are a substrate of CYP3A, CYP2C9, CYP2C19 or P‐glycoprotein, key proteins, involved in the metabolism and/or transport of several drugs .…”

“…This finding is in-line with previous results from other sources that emphasized the critical role of drug-drug interactions with the pharmacological use of this drug class. 1,[30][31][32] Direct antiviral agents are a substrate of CYP3A, CYP2C9, CYP2C19…”

“…When compared to interferon-based therapies, direct-acting antivirals (DAAs) have radically changed the landscape of the pharmacological treatment of hepatitis C virus (HCV) infections by improving survival, leading to higher sustained virological response (SVR) rates, shorter treatment durations, easier administration and fewer HCV infection-related complications. 1,2 However, real-world data suggest that medication errors, such as unnecessary treatment withdrawal, with this class of drug can lead to an imbalance in the benefit-to-risk ratio. [3][4][5] A medication error can be defined as "any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient, or consumer.…”

Management of concomitant hepatocellular carcinoma and chronic hepatitis C: a review

“…The management of HCV has transformed over the past decade, with sustained virologic response (SVR) rates in excess of 95% following treatment with newer directly-acting antiviral agents (DAAs) [18] . Mechanistically, DAAs inhibit viral replication by inhibiting certain non-structural viral proteins, ultimately resulting in viral clearance [19] . DAA use has become more widespread and, with that, our understanding of their interaction with other treatments will improve.…”

Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients

“…Chronic hepatitis C virus (HCV) infection is one of the important causes of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) . Recently, several regimens of direct‐acting antivirals (DAA) combinations have been developed for the treatment of chronic HCV infection . Treatment with DAA can eradicate serum HCV RNA, however, viral mutation was reported after DAA treatment .…”