Potential interactions between pangenotypic direct-acting antivirals and concomitant cardiovascular therapies in patients with chronic hepatitis C virus infection

Abstract

Objective To identify potential drug interactions (DIs) between pangenotypic direct-acting antivirals (pDAAs) and concomitant cardiovascular (CV) therapies in patients with chronic hepatitis C (CHC). Methods A retrospective observational study was carried out. Patients ≥18 years of age diagnosed with CHC and treated with pDAAs during 2017 were included. Information was collected on concomitant CV therapies and potential DIs [ www.hep-druginteractions.org ]. The pDAAs analyzed were sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). An analysis including lipid-lowering drugs was also performed. Results In total, 1286 patients (mean age 64.9 years, 56.6% men) were recruited. The percentages of potential DIs with CV drugs were 1.9% contraindications, 38.1% clinically significant and 2.4% weak. When lipid-lowering drugs were included, the percentages of potential DIs with CV drugs were 10.3% contraindications, 46.3% clinically significant and 3.2% weak. Potential DIs associated with each pDAA were as follows (contraindications; clinically significant; weak): SOF/VEL (1.4%; 23.0%; 0.9%), GLE/PIB (12.8%; 60.8%; 4.7%) and SOF/VEL/VOX (16.6%; 55.1%; 4.9%). Conclusions Approximately on third of patients with CHC are concomitantly treated with CV drugs. SOF/VEL may have fewer DIs with CV drugs than other pDAAs.

Drug–Drug Interactions in Italian Patients with Chronic Hepatitis C Treated with Pangenotypic Direct Acting Agents: Insights from a Real-World Study

“…The concomitant treatments prescribed were in line with the results reported in a Spanish real-world study, in which the most consumed therapeutic groups belonged to the class of alimentary tract and metabolism (37.5%), cardiovascular system (37.5%), and nervous system (34.1%) [15][16][17]. In the Spanish cohort, GLE/PIB showed a higher prevalence of DDIs (17.8%), which was followed distantly by SOF/VEL (2.8%) [15].…”

“…The same tendency was reported in the literature; Schulte et al [ 6 ] showed that contraindications due to DDIs interested 2% of SOF/VEL and 4% of GLE/PIB patients, while Sicras et al [ 15 ] observed that SOF/VEL presented a lower percentage of medication contraindicated compared to GLE/PIB (1.7% vs. 8.3%). There has been reported a greater number of contraindications with cardiovascular co-treatments associated to GLE/PIB vs. SOF/VEL in the Spanish cohort (12.8% GLE/PIB vs. 1.4%) [ 17 ]. These data are aligned with our results (2.7% GLE/PIB vs. few patients with SOF/VEL).…”

“…Clinical trials that investigated the DDI between DAAs and some key drugs generally included patients with limited concomitant medications [ 11 , 12 ]; however, in real life clinical practice, the presence of polypharmacology regimens can make the HCV treatment more challenging than expected [ 13 , 14 , 15 ]. Indeed, studies performed in real-world settings observed among HCV patients high rates of comorbidities and the use of concomitant medication, especially in older ones, which means a greater exposure to potential DDI; moreover, the most commonly concomitant drugs were reported to belong to cardiovascular and central nervous system classes [ 6 , 15 , 16 , 17 ].…”

Impacts of Pharmacists-Managed Outpatient Clinic in patients with Hepatitis C virus infection: A Retrospective Study in China

“…Due to the risk of bradycardia, amiodarone and sofosbuvir containing DAAs are contraindicated, and although the mechanism of this effect is unknown, the use of both drugs together should still be avoided . 23 Induction of CYP3A4 and P-glycoprotein by phenytoin and oxcarbazepine may signi cantly reduce serum concentrations of Elbasvir/grazoprevir and lead to loss of e cacy and potential treatment failure . 24,25 Therefore, pharmacists recommend suspending the use of drugs with contraindications.…”

Italian Real-World Analysis of the Impact of Polypharmacy and Aging on the Risk of Multiple Drug–Drug Interactions (DDIs) in HCV Patients Treated with Pangenotypic Direct-Acting Antivirals (pDAA)

“…To date, several studies in real-life settings reported significant proportions of HCV patients with concomitant morbidities and related medications, mostly related to cardiovascular (CV) or central nervous system (CNS) conditions. 14–16 A previous real-world study by our group conducted in Italy on two cohorts of patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) provided insights on their characteristics and DDI assessment based on the presence of at least one comedication. 16 The present analysis was aimed at an in-depth exploration of the potential impact of polypharmacy regimens and aging on the prevalence of multiple DDIs among patients treated with SOF/VEL or GLE/PIB in settings of daily clinical practice in Italy.…”