The Drug-Drug Interaction Potential of Antiviral Agents for the Treatment of Chronic Hepatitis C Infection

Abstract

Several safe and highly effective direct-acting antiviral (DAA) drugs for chronic hepatitis C virus (HCV) have been developed and greatly increase the number of therapeutic options available to successfully treat HCV infection. However, because treatment regimens contain at least two drugs (e.g., elbasvir and grazoprevir, glecaprevir and pibrentasvir, or sofosbuvir with daclatasvir, simeprevir, ledipasvir, or velpatasvir) and up to five drugs (ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin), the potential for drug-drug interactions (DDIs) becomes an important consideration for HCV-infected individuals with comorbidities that require concomitant medications, such as human immunodeficiency virus/HCV coinfection or immunosuppression after liver transplantation. This review details the pharmacokinetics and DDI potential of approved DAAs for the treatment of HCV infection.

Effectiveness and safety of sofosbuvir‐based therapy against chronic hepatitis C infection after successful kidney transplantation

“…HCV clearance, as observed in most cases after 4 week of therapy, is the key moment when liver function increases sufficiently to affect drug metabolism. As persistently low levels of CNIs can result in acute kidney graft rejection, as observed in previous studies, strict supervision and more‐than‐routine frequent determination of CNI blood trough level are absolutely necessary to ensure treatment safety regardless of the therapeutic regimen . In our group of patients, DAA therapy resulted in significant improvements in liver function tests and liver stiffness measurements, especially in patients with more advanced liver disease.…”

“…As persistently low levels of CNIs can result in acute kidney graft rejection, as observed in previous studies, strict supervision and more-than-routine frequent determination of CNI blood trough level are absolutely necessary to ensure treatment safety regardless of the therapeutic regimen. 43 In our group of patients, DAA therapy resulted in significant improvements in liver function tests and liver stiffness measurements, especially in patients with more advanced liver disease. However, whether this strategy will lead to better long-term patient and kidney graft outcomes remains to be determined in future studies.…”

A changing paradigm: management and treatment of the HCV/HIV-co-infected patient

“…HIV/HCV co-infection has a number of unique features, including faster rates of fibrotic progression [11], increased risk of hepatic decompensation [5], higher HCV viral loads [41], elevated alanine aminotransferase (ALT) levels [42], increased potential for drug–drug interactions [43], and potential for altered absorption of antivirals [44] (Fig. 2).…”

Potential Use of Sofosbuvir in the Prophylaxis for Rabies

“…Cyclosporine, tacrolimus, and methadone increase, whereas rifampin and carbamazepine decrease, the plasma levels of sofosbuvir (Garrison et al, 2018). Sofosbuvir increases the plasma levels of darunavir + ritonavir and norgestrel (Garrison et al, 2018). Finally, current pharmacokinetic data suggest that there should be minimal drug-drug interactions between sofosbuvir and a number of common clinically used drugs.…”

“…Sofosbuvir is a substrate for the intestinal ATP cassette binding (ABC) transporters p-glycoprotein and breast cancer resistant protein; therefore, drugs that inhibit and induce these efflux proteins would increase and decrease, respectively, the plasma levels of sofosbuvir (Kirby et al, 2015). Cyclosporine, tacrolimus, and methadone increase, whereas rifampin and carbamazepine decrease, the plasma levels of sofosbuvir (Garrison et al, 2018). Sofosbuvir increases the plasma levels of darunavir + ritonavir and norgestrel (Garrison et al, 2018).…”