Phenprocoumon and Furosemide Injection: Interaction Details

a) One study has suggested that furosemide may reduce the percentage of phenprocoumon that is protein bound. In therapeutic concentrations (5 mcg/mL (20 mcmol/L)), phenprocoumon was 99.9% bound. When the furosemide concentration was increased from 0 to 400 mcg/mL (1200 mcmol/L) in a Krebs-Henseleit solution, the bound fraction of phenprocoumon was reduced to 25%. The reduction in the percent of phenprocoumon bound was significant only at furosemide concentrations at and above 250 mcg/mL (760 mcmol/L). The decreased binding of phenprocoumon in the presence of furosemide is suggestive that displacement may also occur in vivo ¹.

b) Seven elderly patients (ages 60 to 84 years) were treated with furosemide 40 mg intravenously, followed in four days by phenprocoumon 0.3 mg/kg intravenously. Another dose of furosemide 40 mg was immediately given to determine the free and bound furosemide in the serum. At a therapeutic furosemide concentration (5 mcg/mL (20 mcmol/L)), the average percentage binding in the serum was 96.5% in the elderly subjects and 97.7% in the serum of younger (ages 20-45 years) patients. This difference between older and younger patients is attributed to the fact that elderly patients have reduced concentrations of albumin. During the coadministration of phenprocoumon in concentrations not exceeding 6.2 mcg/mL (22 mcmol/L), the binding of furosemide decreased to 95.8%. This modest decrease in furosemide binding was not considered to be significant ².

c) Furosemide was safely administered to 8 patients receiving phenprocoumon. Phenprocoumon was administered in a dose of 0.22 mg/kg daily for seven days. Following a wash-out period of three weeks, the phenprocoumon dosing was resumed together with furosemide 40 mg twice daily for seven days. During coadministration of these two agents, the plasma half-life, area under the concentration-time curve (AUC), and apparent volume of distribution of phenprocoumon were not altered. There was a slight increase in the renal excretion of unconjugated and conjugated phenprocoumon, suggesting incomplete excretion of these compounds during the control phase. Plasma protein binding of phenprocoumon was 98.3% before and after furosemide. Prothrombin time was not altered with the coadministration of furosemide and phenprocoumon. The authors concluded that furosemide may be safely administered to patients receiving phenprocoumon therapy ³.