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

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.

Fig 1. Number of co-medications used and percentage of patients, by DAA regimen, among HCV-infected patients.

(A) Patients with mild liver disease. (B) Patients with moderate-to severe-liver disease. SOF/RBV: sofosbuvir plus ribavirin, SOF/SIM: sofosbuvir plus simeprevir, SOF/DCV: sofosbuvir plus daclatasvir, SOF/LDV: sofosbuvir plus ledipasvir, 3D: paritaprevir/ritonavir, ombitasvir, dasabuvir. The percentage of patients who took one drug (in blu), two drugs (in red), three drugs (in green) and more than 3 drugs (in violet) are reported considering the total number of patients reported for each regimen in both Fig 1A and Fig 1B at the same manner.

Fig 2. Category of potential DDIs, by DAA regimen and severity of liver disease, among HCV-infected patients.

Comedication used in patients with mild liver disease (A) or in (B) patients with moderate-to severe-liver disease (B). DAA regiments and number of comedications used are shown. SOF/RBV: sofosbuvir plus ribavirin, SOF/SIM: sofosbuvir plus simeprevir, SOF/DCV: sofosbuvir plus daclatasvir, SOF/LDV: sofosbuvir plus ledipasvir, 3D: paritaprevir/ritonavir, ombitasvir, dasabuvir. Category 0: Classification not possible due to lack of information; Category 1: No clinical interaction possible; Category 2: May require dose adjustment/closer monitoring.