Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

PLoS One. 2017 Feb 28;12(2):e0172159. doi: 10.1371/journal.pone.0172159. eCollection 2017.

Abstract

Background: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.

Aim: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.

Methods: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).

Results: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.

Conclusions: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use*
  • Drug Administration Schedule
  • Drug Interactions*
  • Drug Therapy, Combination
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons
  • Italy
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk

Substances

  • Antiviral Agents
  • Interferons

Grants and funding

The authors received no specific funding for this work. However, the PITER platform has been supported by Italian Ministry of Health Grant “Research Project PITER2010” RF-2010-2315839 to SV.