title: Drug-Drug Interactions With Novel All Oral Interferon-Free Antiviral Agents in a Large Real-World Cohort.
abstract: BACKGROUND
  With the approval of direct-acting antivirals (DAAs), the management of drug-drug interactions (DDIs) has become an important challenge while treating individuals with hepatitis C. To date, the potential of causing DDIs for the recently approved DAAs has not been systematically investigated. We aimed to assess the clinical significance of DDI between the regular outpatient medications and DAA therapies in a large real-world cohort.
  
  
  METHODS
  Overall, 261 hepatitis C virus monoinfected patients who were selected for DAA therapy at 2 intervals between 2011 and 2014 were asked about their regular outpatient medications. The potential for DDIs between all these drugs and sofosbuvir/ribavirin, ledipasvir/sofosbuvir, sofosbuvir/daclatasvir, sofosbuvir/simeprevir, ombitasvir/paritaprevir/ritonavir ± dasabuvir as well as boceprevir and telaprevir triple therapy was assessed using www.hep-druginteractions.org and the relevant prescribing information.
  
  
  RESULTS
  The 261 patients took a median number of 2 drugs (range 0-15); 20% of patients did not take any medication. Sofosbuvir/ribavirin had the lowest risk to cause a potentially significant DDI (9.6%). In contrast, for ombitasvir/paritaprevir/ritonavir ± dasabuvir potentially significant DDIs could be expected in 66.3% of the patients. Significant DDIs for sofosbuvir/simeprevir would be expected in 31.4%, for sofosbuvir/daclatasvir in 36.8%, and for sofosbuvir/ledipasvir in 40.2%. Proton pump inhibitors, thyroid hormones, and dihydropyridine derivatives were frequently used and presented a risk of interacting with the antiviral regimen.
  
  
  CONCLUSIONS
  A significant number of patients are at risk for DDIs if treated with the recently approved DAA regimens. A careful evaluation of potential DDI is essential to prevent adverse effects or unnecessary risk of treatment failure.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Höner Zu Siederdissen
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Maasoumy
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool Pharmacy Department, Gartnavel General Hospital, Glasgow, Scotland, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Marra
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Deterding
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Port
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool.
authors.forename: David
authors.initials: D
authors.lastname: Back
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004347:Drug Interactions; D006526:Hepatitis C / Q000188:drug therapy*; D010045:Outpatients
chemical_list: D000998:Antiviral Agents
keywords: antiviral therapy; cytochrome P450; direct-acting antiviral agents; drug–drug interactions; hepatitis C virus