Bosentan and warfarin interaction

Objective: To report a case of decreased international normalized ratio (INR) in a patient receiving warfarin and bosentan. Case Summary: A 35-year-old African American woman with a history of primary pulmonary hypertension managed with warfarin, diltiazem, and hydrochlorothiazide was initiated on bosentan therapy. The patient's INR had been stable and within therapeutic range (goal 2.0-3.0) for the previous 3 months with warfarin 27.5 mg/wk, but became subtherapeutic after 10 days of bosentan therapy Addition of over-the-counter medications, herbal products, vitamins, or dietary changes was denied. The INR remained subtherapeutic for 5 weeks despite weekly warfarin dose increases. After these 5 weeks of dosage increases, the INR became supratherapeutic for 3 weeks, resulting in a subsequent dosage decrease. The resultant warfarin dose required to maintain a therapeutic INR was 45 mg/wk, a 63.6% dosage increase after the initiation of bosentan. Discussion: This case shows that a clinically significant interaction between bosentan and warfarin may exist. An objective causality assessment revealed that the interaction was probable. Although the possibility of this interaction has been noted, no previously documented occurrence of this interaction has been identified. Conclusions: Bosentan may significantly decrease the anticoagulant properties of warfarin. The INR should be monitored more frequently when bosentan is initiated, adjusted, or discontinued in patients taking warfarin.