Probable Warfarin and Dapsone Interaction

We describe a case of a 41-year-old woman who was stable for over a year on 22.5 mg/week of warfarin. At a follow-up visit, her international normalized ratio (INR) was found to be supratherapeutic at 3.9. Her only significant change was acyclovir initiation for shingles, and clindamycin and dapsone for infection on her right foot. An interaction report was run using Micromedex with no interactions reported. Sixteen percent of the weekly dose was held and maintenance dose was continued. Two weeks later, the INR remained supratherapeutic at 4.3, with discontinuation of clindamycin and dapsone, 5 days earlier, as the only change. This time an interaction report was run using Lexi-Comp, which identified an interaction between warfarin and dapsone. The INR has been therapeutic and stable since discontinuation of transient factors. It is hypothesized that warfarin and dapsone compete for binding on the CYP2C9 and CYP3A4 isoenzymes and therefore serum concentration of warfarin was elevated.