Polypharmacyand prevalence of multi drug-drug interactions in hepatitis C patients treated with pangenotypic direct acting antivirals: an analysis from three European countries

Background Various guidelines recommend thorough drug–drug-interaction (DDI) evaluation before starting pangenotypic direct-acting antiviral (pDAA) therapy.

Studies have analyzed DDIs in HCV-patients receiving pDAAs and comedications only by pairwise interaction which does not reflect the polypharmacy in HCV-patients. This study aimed to evaluate the proportion of HCV-patients with multiple comedications causing potential DDIs in three European countries.

Method Prescription data of pDAA treated HCV-pts from Germany, Italy, and Spain were collected. DDIs were identified using Liverpool-database. Multi-DDI profile was defined as the use of≥2 comedications each predicted with a DDI specific to the used pDAA . Potential DDIs were summarized as an increase in comedication exposure (safety impact) or a decrease in DAA exposure (efficacy impact).

Results 10,755 HCV-pts were treated with sofosbuvir/velpatasvir (n=4583) or glecaprevir/pibrentasvir (n=6172). Patients: 4950 German, 4185 Italian, and 1620 Spanish. 58.9% received any comedication during pDAA therapy, and 20.2% were at risk of DDI. Multi-DDI risk: 566 patients were taking≥2 comedications, each with a potential DDI with their pDAA, representing 5.3% of HCV-patients and 8.9% receiving any comedication. Evaluation of predicted DDI impact: 23.9% of patients taking≥2 comedications risked efficacy impact, mainly due gastrointestinal drugs and analgesics. 26.5% risked safety impact, mainly due cardiovascular and nervous system drugs.

Conclusion 8.9% of analyzed pts taking medications during pDAA therapy are at risk of multi-DDIs. Accurate prediction of the impact on efficacy and safety is difficult. A thorough pDDI assessment before HCV therapy in comorbid patients is recommended.

Publication History

Article published online:
18 January 2023