Background and importance Treatment of chronic hepatitis C (CHC) has become simpler and more effective since the introduction of pan-genotypic direct acting antiviral agents (DAA), but contraindicated drug–drug interactions (DDI) with DAA should be carefully evaluated to avoid the risk of side effects or loss of treatment efficacy.

Aim and objectives To investigate the patterns of contraindicated DDI with pan-genotypic DAA in real world practice.

Material and methods We conducted a retrospective cohort study by analysing the Chang Gung Research Database, a multi-institutional electronic medical records database which covers 1.3 million individuals (6% of the Taiwan population). We included CHC patients newly receiving pan-genotypic DAA (eg, glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL)) from 1 August 2018 to 31 September 2019. We identified drugs with contraindicated DDI following the HEP Drug Interaction Checker and pharmaceutical package insert. We calculated the numbers and rates of exposure to contraindicated DDI 3 months prior to initiation of pan-genotypic DAA, and evaluated the changes under pan-genotypic DAA treatment.

Results We included 1311 and 239 CHC patients newly receiving GLE/PIB and SOF/VEL, respectively. Before pan-genotypic DAA treatment, 33 (2.5%) and 3 (1.3%) patients receiving GLE/PIB and SOF/VEL, respectively, received prescriptions involving contraindicated DDI. Among the prescriptions with contraindicated DDI with GLE/PIB, 25 (75.8%) included lipid lowering agents and 6 (18.2%) included anticonvulsants. Among those with contraindicated DDI with SOF/VEL, 2 (66.6%) were for anticonvulsants and 1 (33.3%) involved a nucleoside reverse transcriptase inhibitor. After initiation of pan-genotypic DAA, we found exposure to contraindicated DDI decreased to 14 patients (1.1%) for those receiving GLE/PIB treatment. No change in contraindicated DDI exposure was observed in patients receiving SOF/VEL treatment.

Conclusion and relevance The rate of exposure to contraindicated DDI generally decreased after initiation of pan-genotypic DAA, but some contraindicated drugs remained co-prescribed. Future studies are required to evaluate the outcomes in patients exposed to contraindicated DDI.

Conflict of interest No conflict of interest