Predicting Daily Maintenance Dose of Fluindione, an Oral Anticoagulant Drug

Summary

Due to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p<0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

• References

• 1 Williams DB, Karl RC. A simple technic for predicting daily maintenance dose of warfarin. Am J Surg 1979; 137: 572-576
• 2 Fennerty A, Dolben J, Thomas P, Backhouse G, Bentley DP, Campbell IA, Routledge PA. Flexible induction dose regimen for warfarin and prediction of maintenance dose. Br Med J 1984; 228: 1268-1270
• 3 Miller DR, Brown MA. Predicting warfarin maintenance dosage based on initial response. Am J Hosp Pharm 1979; 36: 1351-1355
• 4 Routledge PA, Davies DM, Bell SM, Cavanagh JS, Rawlins MD. Predicting patient’s warfarin requirements. Lancet 1977; 02: 854-855
• 5 Tillement JP, Thebault JJ, Mattei C, Athis P, Blatrix C. Anticoagulant effect and plasma kinetics of fluorophenindione after a single dose in man. Eur J Clin Pharmacol 1975; 8: 271-275
• 6 Fiessinger JN, Paul JF. Le relais heparine-antivitamine K. STY 1992; 4: 7-10