Elsevier

Journal of Hepatology

Volume 58, Issue 4, April 2013, Pages 792-800
Journal of Hepatology

Review
Clinical management of drug–drug interactions in HCV therapy: Challenges and solutions

https://doi.org/10.1016/j.jhep.2012.10.027Get rights and content
Under a Creative Commons license
open access

Summary

Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug–drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug–drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted drug–drug interaction studies and a list of contraindicated medications is not enough for the clinical management of these drug–drug interactions. Knowledge of pharmacokinetic profiles and concentration–effect relationships is key for the interpretation of these data, and insight into how to manage these interactions (e.g., dose adjustments, safe alternatives and therapeutic drug monitoring) is of equal importance. This review provides a practical overview of the safe and effective management of these clinical challenges.

Abbreviations

HCV
hepatitis C virus
DAAs
direct-acting antivirals
HIV
human immunodeficiency virus
SPCs
summary of product characteristics
Peg
polyethylene glycol
BID
twice daily
AKR
aldo-ketoreductases
P-gp
P-glycoprotein
AUC
area under the plasma concentration vs. time curve
FDA
Food and Drug Administration
EMA
European Medicines Agency
TDM
therapeutic drug monitoring
CYP
cytochrome P450
ECG
electrocardiogram
UGT
UDP-glucuronosyltransferase
ACE
angiotensin converting enzyme
AT1
angiotensin II receptor
PDE5
phosphodiesterase type 5
BOC
boceprevir
TVR
telaprevir
RBV
ribavirin
IFN
interferon

Keywords

Drug interactions
Hepatitis C virus infection
Boceprevir
Telaprevir
Pharmacokinetics

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