title: The clinical significance of drug-drug interactions in the era of direct-acting anti-viral agents against chronic hepatitis C.
abstract: BACKGROUND
  Drug-drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct-acting anti-virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P-glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.
  
  
  OBJECTIVE
  To analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.
  
  
  METHODS
  The first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co-medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information.
  
  
  RESULTS
  Out-patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0-11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co-medication in 7% and 21% of the patients respectively.
  
  
  CONCLUSIONS
  Many patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co-medication is strictly incompatible. Overall, the challenge of DDIs is time-consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.
authors.affiliation: Department for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Maasoumy
authors.forename: K
authors.initials: K
authors.lastname: Port
authors.forename: B
authors.initials: B
authors.lastname: Calle Serrano
authors.forename: A A
authors.initials: AA
authors.lastname: Markova
authors.forename: L
authors.initials: L
authors.lastname: Sollik
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: M
authors.initials: M
authors.lastname: Cornberg
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011480:Protease Inhibitors / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline