title: Real-life data on potential drug-drug interactions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study.
abstract: BACKGROUND
  There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used.
  
  
  OBJECTIVE
  To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study.
  
  
  METHODS
  Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org).
  
  
  RESULTS
  Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI.
  
  
  CONCLUSIONS
  Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Loreta A
authors.initials: LA
authors.lastname: Kondili
authors.affiliation: Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Gaeta
authors.affiliation: Clinical Unit of Gastroenterology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ieluzzi
authors.affiliation: Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
authors.affiliation: Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Soria
authors.affiliation: Department of Internal Medicine, University Hospital of Messina, Messina Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raimondo
authors.affiliation: Department of Internal Medicine, University Hospital of Messina, Messina Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Filomia
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Iannone
authors.affiliation: Infectious Diseases, Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Massari
authors.affiliation: Infectious Diseases, Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia, Reggio Emilia, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Corsini
authors.affiliation: Infectious Diseases, University of Pavia, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gulminetti
authors.affiliation: Infectious Diseases, University of Pavia, Pavia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gatti Comini
authors.affiliation: Gastroenterology, Department of Surgical and Gastroenterological Sciences, University of Udine, Udine, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.affiliation: Gastroenterology, Department of Surgical and Gastroenterological Sciences, University of Udine, Udine, Italy.
authors.forename: Denis
authors.initials: D
authors.lastname: Dissegna
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Russo
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanetto
authors.affiliation: Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.affiliation: Infectious Diseases, Second University of Naples, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Brancaccio
authors.affiliation: Division of Infectious Diseases, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Danieli
authors.affiliation: Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
authors.forename: Maurizia Rossana
authors.initials: MR
authors.lastname: Brunetto
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Liliana Elena
authors.initials: LE
authors.lastname: Weimer
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Quaranta
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
authors.affiliation: Division of Infectious Diseases, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D007558:Italy; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk
chemical_list: D000998:Antiviral Agents; D007372:Interferons