Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study.

BACKGROUND Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding. METHODS The study was a prospective randomized controlled trial of consecutive patients presenting with excessive anticoagulation without major bleeding. Patients with a baseline international normalized ratio (INR) of 6 to 10 (n = 44, 47 episodes) received either intravenous or oral phytonadione (0.5 mg or 2.5 mg, respectively), and patients with an INR greater than 10 (n = 17, 19 episodes) received 1 mg or 5 mg, respectively. Efficacy and safety end points were sequential INR changes and the proportion of patients achieving therapeutic range (INR, 2-4), overcorrection (INR<2.0), or undercorrection (INR>4.0) INR values. RESULTS Sixty-six episodes of excessive anticoagulation were studied. In patients with baseline INR 6-10 the response to intravenous phytonadione was more rapid than in the oral group, and the proportion of patients reaching therapeutic range INR at 6 hours (11/24 vs 0/23) and at 12 hours (16/24 vs 8/23) was significantly higher. However, mean +/- SD INR values were similar for both groups at 24 hours (2.9 +/- 0.8 vs 2.6 +/- 0.8). Patients in the intravenous group tended to be more often (7/24 vs 2/23) overcorrected (INR<2). In patients with baseline INR values greater than 10 efficacy and safety were comparable for both routes of administration. CONCLUSION Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.