Pharmacokinetics and important drug–drug interactions to remember when treating advanced chronic kidney disease patients with hepatitis C direct acting anti‐viral therapy

Abstract

Hepatitis C direct acting antiviral (DAA) therapy has evolved so that infected patients with advanced chronic kidney disease (CKD) can now anticipate the opportunity for sustained virologic response equivalent to that of the broader population of patients with hepatitis C. This has revolutionized the field of transplantation as it relates to renal transplant candidates with hepatitis C and the use of grafts from hepatitis C virus (HCV) viremic donors. In treating this population of patients, special consideration must be given to the timing of anti-viral therapy and drug-drug interactions. Herein we review the pharmacokinetics of HCV DAA therapy in the setting of CKD and chronic renal replacement therapy. Highlighted are drug/drug interactions with special attention to therapies utilized in advanced CKD and immunosuppressants.

Potential interactions between pangenotypic direct-acting antivirals and concomitant cardiovascular therapies in patients with chronic hepatitis C virus infection

“…Other studies reported similar or substantially higher percentages of DIs. [10][11][12][13]21 Our results agree with those of previous studies, although we recorded a lower proportion of clinically relevant drug interactions. This may be because our study was conducted with the more recently marketed pDAAs.…”

“…10 In addition, DIs with therapies used to treat comorbidities may contraindicate the use of pDAAs. [10][11][12] A recent study conducted in Spain reported high rates of comorbidities and concomitant medication rates in patients with HCV. The most commonly prescribed therapies with potential DIs were those related to the cardiovascular (CV) system and the central nervous system.…”

“…13 Careful review of the medications used by patients with HCV is therefore advisable. 2,[10][11][12][13] Little information is currently available on the true risks of DAAs based on patterns of concomitant medication use at the population level. The objective of our study was thus to identify DIs between pDAAs and concomitant CV therapies in patients with HCV in standard clinical practice in Spain.…”

Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC)

“…Similar to non-transplant HCV-infected patients, response to treatment should be monitored with PCR testing at least at the end of the treatment course and 12 weeks after treatment cessation. To date, there is no evidence that transplanted patients respond differently to DDA treatment than the non-transplanted population (56,(90)(91)(92). Non-infection or sustained virological response can reasonably be ascertained with a negative HCV-PCR test 12 weeks after completion of treatment.…”

Introduction to hepatitis C virus infection in patients with kidney disease: A roadmap for nephrologists

“…Their review encompasses both randomized trials and real‐world experience and underscores the excellent efficacy and safety profiles of several of the DAA therapies in patients with impaired kidney function . This segues into the next article, by Cohen and Liapakis, who provide detailed insight into the pharmacokinetics of the DAA therapies, as well as important drug‐drug interactions to be cognizant of when treating patients with abnormal kidney function, including those on dialysis and/or on chronic transplant immunosuppression . Pagan and Roth extensively review the data on DAA treatment in ESRD patients.…”