Warfarin and ARVs: impact of African American race and ritonavir
Simon Collins, HIV i-Base
The commonly prescribed anticoagulant warfarin is highly susceptible to interactions with antiretroviral mediated through CYP 2C9, 2C19, and/or 3A4 pathways, although data are limited.
This retrospective, case-control (1:2) study compared the warfarin maintenance dose (defined as the dose required to maintain goal INR) between patients on ART (n=18) and patients not on ART (n=36). ART was PI-based (n=9: mainly lopinavir/r), NNRTI-based (n=7, mainly efavirenz), and PI+NNRTI-based (n=2). The warfarin maintenance dose (mean±SD) differed significantly between cases and controls (8.6±3.4 mg vs 5.1±1.5 mg, p<0.01), but not across ART regimens (PI: 8.8±4.6 mg; NNRTI: 8.6±1.8 mg; PI+NNRTI: 7.3±3.3 mg; p=0.86).
African American race and ritonavir dose were independent predictors of warfarin dose; with an expected increase by 3.9 mg ([95%CI: 0.88-7.0], p=0.02) if African American or by 3.7 mg ([95%CI: 0.53-6.9], p=0.03) if the total daily ritonavir dose is 200 mg. Higher empiric warfarin doses and/or more vigilant monitoring and dosage adjustments may be required in these patients.
Darin KM et al. The clinical implications of antiretroviral drug interactions with warfarin: a case-control study. 13th PK Workshop, 16-18 April 2012, Barcelona. Abstract: P_18.