title: Directly acting antivirals for hepatitis C and antiretrovirals:  potential for drug-drug interactions.
abstract: OBJECTIVE
  Boceprevir and telaprevir are directly acting antivirals (DAAs) that have recently been licensed for treatment of hepatitis C virus (HCV) infection. Data in both untreated and previously treated patients indicate a significantly increased sustained virological response (SVR) compared with that observed with conventional therapy. However, the advent of DAA therapy poses specific challenges for HCV treatment in terms of managing drug-drug interactions (DDIs). This review aims to provide a comprehensive summary of DDI with the recently licensed DAAs, including pharmacokinetic data and current recommendations made by the manufacturers and with particular reference to antiretrovirals. Potential for DDIs with the DAAs in clinical development and the mechanisms of interaction are also discussed.
  
  
  RESULTS
  Targeted pharmacokinetic drug interaction studies have demonstrated that both boceprevir and telaprevir are potent inhibitors of the metabolic enzyme cytochrome P4503A4, making them perpetrators of interactions with co-administered medications which are metabolized by this enzyme. In addition, co-administered medications may affect plasma levels of boceprevir and telaprevir via various mechanisms, some of which remain to be fully elucidated.
  
  
  CONCLUSIONS
  As a result of DDIs, the concomitant use of some medicines with DAA will be contraindicated, whereas other combinations may require caution, monitoring, or dose modification of the co-administered drug. Management of DDIs with these novel agents will pose a new challenge, and prescriber awareness of the potential for DDIs is fundamental for safe prescribing. Online resources are likely to play a key role in prescriber education and clinical decision-making.
authors: NIHR Biomedical Research Centre, Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, UK. k.seden@liv.ac.uk
authors: Kay
authors: K
authors: Seden
authors: David
authors: D
authors: Back
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D060085:Coinfection; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; 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