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  The International Liver Congress™
EASL - European Association for the
Study of the Liver
June 22-26 2022
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Risk of Dangerous Interactions When Giving DAAs With Other Meds
  EASL International Liver Congress 2022, London, June 22-26, 2022
Mark Mascolini
Nearly 10% of 10,755 HCV patients prescribed comedications with a pangenotypic direct-acting antiviral (pDAA) ran a risk of multiple drug-drug interactions (DDI) in Germany, Italy, and Spain [1]. Researchers from Charité-Universitatsmedizin Berlin and colleagues at other centers urged colleagues to assess DDI potential thoroughly before starting DAAs, particularly in people taking cardiovascular or nervous system drugs.
The researchers noted that pDAAs share drug-metabolizing pathways with many medications frequently prescribed for people with HCV infection. Liver groups like EASL, AASLD, and APASL recommend careful analysis of potential DDIs when starting a pDAA and before starting comedications with a pDAA.
This prospective 2017-2020 observational study in Germany, Italy, and Spain aimed to estimate the proportion of pDAA-treated people who ran a heightened risk of adverse events resulting from multiple potential DDIs. The researchers defined multiple DDIs as 2 or more comedications having a DDI with a pDAA. Study participants took either sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). The investigators identified potential DDIs with the University of Liverpool's online hepatitis drug interaction tool ( https://www.hep-druginteractions.org/).
The analysis involved 10,755 people with HCV, 64% of them male, averaging 50.7 years in age. While 57% took GLE/PIB, 43% took SOF/VEL. There were 4950 participants in Germany, 4185 in Italy, and 1620 in Spain.
Across the three countries, 8.9% of participants taking comedications with pDAAs were at risk for 2 or more predicted DDIs. Another 25.4% ran a risk of 1 predicted DDI. People with multiple potential DDIs averaged 63.6 years in age, compared with 50.7 years in the entire study group. Among people at risk for multiple DDIs, 8.1% in Germany, 14.1% in Italy, and 17.9% in Spain had been prescribed 1 or more contraindicated comedications.
In people predicted to have multiple DDIs, about one quarter (23.9%) risked higher comedication levels because of a potential DDI, which could compromise the safety of the comedication. Agents with potential increased exposure were often cardiovascular drugs (such as statins) and nervous system drugs (such as antipsychotics). In this group with predicted multiple DDIs, one quarter (24.0%) could have a DDI that could lower pDAA concentrations, which could impair their antiviral impact. This potential type of DDI usually involved gastrointestinal comedications (such as proton pump inhibitors) and analgesics (such as metamizole).
The research team recommended "thorough DDI assessment" before starting a pDAA in people with comorbidities, especially those requiring treatment with cardiovascular agents or nervous system drugs.
EASL: Polypharmacy and prevalence of multiple drug-drug interactions in hepatitis C patients treated with pangenotypic direct-acting antivirals: an analysis from three European countries - (06/24/22)
1. Tacke F, Turnes J, Hintz A, et al. Polypharmacy and prevalence of multi drug-drug interactions in hepatitis C patients treated with pangenotypic direct acting antivirals: an analysis from three European countries. EASL International Liver Congress 2022, London, June 22-26, 2022. Abstract FRI393.