Potential interaction involving warfarin and ritonavir

To report an unexpected decrease in warfarin effect following the addition of ritonavir to the medication regimen.

A 27-year-old patient with advanced HIV taking warfarin for an inferior vena cava thrombus was started on ritonavir, clarithromycin, and zidovudine. The international normalized ratio (INR) decreased over a period of weeks after the addition of ritonavir, clarithromycin, and zidovudine to the drug therapy regimen. The warfarin dosage was almost doubled in order to maintain a therapeutic INR. Months later, when ritonavir alone was discontinued, the INR rose rapidly and the warfarin dose requirements decreased significantly.

Potential interactions between warfarin and the protease inhibitors are described in the literature. Ritonavir has been shown to be a potent inhibitor of CYP3A4, an enzyme responsible for warfarin metabolism. Potentiation of warfarin effect and subsequent decrease in the warfarin dosage requirement was anticipated following ritonavir administration; however, the opposite occurred. The mechanism of the potential interaction between warfarin and ritonavir is not known, and may represent a complex, multidrug interaction. The paradoxical decrease in the INR is particularly intriguing.

Frequent, careful monitoring of warfarin is recommended when ritonavir therapy is initiated or discontinued in a patient taking warfarin. The potential for either an increase or decrease in the INR should be anticipated.