Affiliation:
1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
2. German Center for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), partner site Hannover-Braunschweig, Hannover, Germany
3. University of Liverpool, Clinical Pharmacology, Liverpool, United Kingdom
4. Department of Clinical Pharmacology, Hannover Medical School, Hannover, Germany
Abstract
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.
Funder
German Center for Infection Research
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Oncology
Cited by
17 articles.
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