Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Abstract

The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3) and 50% (genotype 1) were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

“…However, further analyses are required to demonstrate the predictive value of baseline viral load and RVR achievement on SVR rates in a cohort of Brazilian patients. The long-term safety profile of protease inhibitors is also an important aspect to be evaluated in real-life studies, because first-generation agents are associated with adverse events (cutaneous rash was found to be related to telaprevir treatment and dysgeusia and anemia were related to boceprevir treatment) 33. Therefore, further analysis addressing the adverse events associated with these agents should be conducted.…”

Latest advances in the efficacy, tolerability, and monotherapy of integrase inhibitors

“…Based on international guidelines and the large clinical trials mentioned earlier (22)(23)(24): i) most international guidelines recommend DTG as an integral part of initial treatment; ii) data from a number of clinical trials support the use of DTG, which has a high level of antiviral efficacy; iii) DTG is administered once daily in a small dose with no need for synergistic action of other drugs and can be administered at any time; iv) DTG interacts little with commonly used drugs; and v) HIV is unlikely to develop resistance to DTG.…”

Safely treating hepatitis C in patients with HIV or hepatitis B virus coinfection

“…Advantages of the newer DAAs are once-daily dosing, IFN free, high response rate, low adverse events and shorter treatment duration. There are also multiple reviews summarizing the drug interactions between approved and upcoming DAAs and commonly used ART agents [58,82,83]. These summaries are practical for selecting an appropriate regimen in HCV/HIV-coinfected patients.…”