Is there an interaction between warfarin and polyestradiol that would cause a decrease in the patie

Fråga: Is there an interaction between warfarin and polyestradiol that would cause a decrease in the patient´s PK?

Background: A 76-year-old man has been taking polyestradiol (Estradurin) 240 mg every 6 weeks for prostate cancer (diagnosed 1993), since March of 1995. He began taking warfarin (Waran) 27.5 mg per week in September of 1996. His prothrombin complex (PK) measurements have been 15-18. The most recent one, taken on 19/2 was 9. The physician would like to know if there is an interaction between these two agents that would cause such a decrease in the PK.

Sammanfattning: It seems highly unlikely that the decreased PK in this patient was due to a drug interaction between warfarin and estrogens as a group, of which polyestradiol is one. Therefore the possibility of other causes to his decreased PK value should be considered, such as decreased liver function due to liver metastases.

Svar: There is no primary literature concerning interactions specifically between warfarin and polyestradiol. There is, however, literature which sites that estrogens as a group, will increase the PK of patients on warfarin therapy.

Warfarin works by sequentially inhibiting Factors VII, IX, X and II (1). Polyestradiol though, can cause an increased prothrombin, as well an increase in Factors VII, VIII, IX, and X (1).

Another source indicates that oral contraceptives will increase the clotting factor concentrations, thus raising the PK (2). Although polyestradiol is not the exact same thing as the estrogens found in oral contraceptives, there is more estrogen found in polyestradiol than in oral contraceptives (1).

Additionally, estrogens are listed as a class of drugs that will increase the synthesis of clotting factors in a table of significant warfarin drug interactions (3).