title: Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.
abstract: OBJECTIVE
  Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART.
  
  
  METHODS
  This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD.
  
  
  RESULTS
  We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P < 0.01), more often male (72.2% versus 36.1%, P=0.02) and more likely to be African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ± SD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ± 1.5 mg, P < 0.01), but not ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ± 1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg.
  
  
  CONCLUSIONS
  The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.
authors: Department of Pharmacy Practice, Chicago State University College of Pharmacy, 9501 S. King Drive, DH 206, Chicago, IL 60628, USA.
authors: John S
authors: JS
authors: Esterly
authors: Kristin M
authors: KM
authors: Darin
authors: Lana
authors: L
authors: Gerzenshtein
authors: Fidah
authors: F
authors: Othman
authors: Michael J
authors: MJ
authors: Postelnick
authors: Kimberly K
authors: KK
authors: Scarsi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D044383:Black People; D016022:Case-Control Studies; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000517:prevention & control; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use; D044465:White People; D001741:Black or African American
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D014859:Warfarin
keywords: HIV; anticoagulation; non-nucleoside reverse transcriptase inhibitors; protease inhibitors; venous thromboembolism