The majority of hepatitis C patients treated with direct acting antivirals are at risk for relevant drug-drug interactions

Abstract

Background: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions.

Objective: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients.

Methods: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use. We compiled a list of currently available direct-acting antiviral regimens and cross-checked for potential drug-drug interactions with used co-medication.

Results: The cohort included 461 patients of which 77% used co-medication. We identified 260 drugs used as co-medication. Antidepressants (7.4%), proton pump inhibitors (7.1%) and benzodiazepines (7.1%) were most frequently used. Of the patients, 60% were at risk for a clinically relevant drug-drug interaction with at least one of the direct-acting antiviral regimens. Interactions were most common with paritaprevir/ritonavir/ombitasvir/dasabuvir and least interactions were predicted with grazoprevir/elbasvir.

Conclusion: Co-medication use is rich in frequency and diversity in chronic hepatitis C patients. The majority of patients are at risk for drug-drug interactions which may affect efficacy or toxicity of direct-acting antivirals or co-medication. The most recently introduced direct-acting antivirals are associated with a lower risk of drug-drug interactions.

Keywords: Hepatitis C; NS5A-inhibitor; NS5B-inhibitor; Protease inhibitor; antiviral therapy; drug-drug interactions; pharmacokinetics.

Figure 1.

Overview of concomitant medication and predicted number of drug-drug interactions (DDIs) between the direct-acting antiviral regimens and 260 different compounds. Sofosbuvir (SOF), simeprevir (SIM), and daclatasvir (DCV) are licensed as separate compounds for hepatitis C virus (HCV)-infected patients. These drugs are separately available in the University of Liverpool database. However, we present these regimes together, because in clinical practice these drugs are used in combination. DDIs with paritaprevir (PTV)/ritonavir (r), ombitasvir (OBV) plus dasabuvir (DSV), ledipasvir (LDV) plus SOF, velpatasvir (VEL) plus SOF, and elbasvir (EBR) plus grazoprevir (GZR) were available per combination in the University of Liverpool database.

Figure 2.

Risk of a clinically relevant drug-drug interaction (DDI) per patient (n = 461), grouped per direct-acting antiviral regimen. DCV: daclatasvir; DSV: dasabuvir; EBR: elbasvir; GZR: grazoprevir; LDV: ledipasvir; OBV: ombitasvir; PTV: paritaprevir; r: ritonavir; SIM: simeprevir; SOF: sofosbuvir; VEL: velpatasvir.