Frequency of Potential Drug–Drug Interactions in the Changing Field of HCV Therapy

Abstract

Background With the introduction of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, drug–drug interactions (DDIs) emerged as significant challenge. Since then, HCV therapy and the infected population have rapidly changed. So far, very limited data are available regarding the clinical relevance of DDIs when using most modern DAA regimens. We aimed to assess how the importance of DDIs has evolved over time. Methods From January 2014 to July 2018, 668 consecutive HCV patients were evaluated for their outpatient medication and assessed for DDIs with DAAs. Different time periods were defined based on market approval of key DAAs: A (01/2014–11/2014), B (11/2014–08/2016), and C (08/2016–07/2018). Results The frequency of patients with real-world DDIs was highest in period B (A: 37.1%, B: 49.6%, C: 38.8%). The recently approved DAAs (period C) theoretically showed a lower DDI risk profile. However, real-world DDIs were still comparable to period A, as HCV patients’ characteristics changed (eg, age ≥75 years: A: 3.1%, B: 9.8%, C: 5.6%; polypharmacy/patients with ≥8 drugs: A: 11.1%, B: 15.2%, C: 17.2%). Furthermore, although DDIs via CYP 3A4 became less important for some modern regimens, other mechanisms like an altered pH value in the stomach, causing reduced bioavailability, evolved. Relevant DDIs most frequently occurred with proton pump inhibitors, metamizole, statins, and carvedilol. Conclusions DDIs during antiviral treatment still affect about 40% of HCV patients. The lower DDI potential of modern DAA regimens is partly counteracted by changing patient characteristics. Therefore, DDIs should not be underestimated.

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

“…25 The results of our study regarding potential DIs with statins have also been reported in other published studies. 26 …”

Direct-acting antiviral treatments display excellent outcomes even in older HCV-infected patients at increased risk of fibrosis

“…Thus, any selection of DAA regimens for older HCV patients should be made carefully. In addition, potential drug-drug interactions (DDIs) should not be underestimated or ignored, especially in the ritonavir-based regimen (35). Our results provide evidence that the presence of these comorbidities in older patients is not a barrier to achieving a SVR.…”

Prevalence of drug-drug interactions with pangenotypic direct-acting antivirals for hepatitis C and real-world care management in the United States: a retrospective observational study

“…Although it is not possible to compare recommendations to avoid DDIs across studies, failure to follow recommendations to avoid DDIs was also seen in a significant proportion of patients (40%) in a large real-world study. 17 In the future, it will be important to collect specific reasons for not accepting recommendations to explore potential avenues for reducing potential DDIs. Awareness of DDIs is of paramount importance, and care could also be improved by inclusion of the Hepatitis Drug Interaction Database as a resource for pharmacists along with currently used sources (Micromedex, Facts and Comparisons, UpToDate, Lexicomp, and package inserts).…”

“…DDIs with lipid-lowering agents have previously been reported to be most frequent with regimens containing NS34A serine protease inhibitors. 17 EMR and pharmacy data suggest that population characteristics are highlight the importance of safety considerations and individualized therapies even for pangenotypic DAA regimens for chronic HCV, especially as treatment is expanded to high-risk populations to meet the WHO goal of HCV elimination.…”