title: A probable interaction between warfarin and the antiretroviral TRIO study regimen.
abstract: OBJECTIVE
  To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient.
  
  
  METHODS
  In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0).
  
  
  CONCLUSIONS
  Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction.
  
  
  CONCLUSIONS
  An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.
authors.affiliation: Department of Pharmacy, Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. michelle-liedtke@ouhsc.edu
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Liedtke
authors.forename: Amulya
authors.initials: A
authors.lastname: Vanguri
authors.forename: R Chris
authors.initials: RC
authors.lastname: Rathbun
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D020246:Venous Thrombosis / Q000188:drug therapy; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D017320:HIV Protease Inhibitors; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D014859:Warfarin; D000069454:Darunavir