Is there any dosage scheme used in transition from phenprocoumon to warfarin?/nThe question concern

Fråga: Is there any dosage scheme used in transition from phenprocoumon to warfarin?

The question concerns a patient who has been treated with phenprocoumon (Marcoumar) in Germany, but now will switch to warfarin (Waran) for continued anticoagulant therapy.

Sammanfattning: One transition scheme has been described in the literature. However, the safety of this scheme is unclear. A well established alternative is therefore to give a LMWH after phenprocoumon discontinuation and the following INR normalisation; and continue with LMWH in parallel with the start of warfarin therapy until a therapeutic INR has been reached.

Svar: Phenprocoumon is a coumarin derivative with a pharmacological action identical to warfarin (1). However, the pharmacokinetic properties differ with a slower elimination of phenprocouomon. The half-life of phenprocoumon is in average 144 hours compared to 40 hours for warfarin. Therefore, the warfarin dose has to be introduced carefully after termination of phenprocoumon to avoid overdosing (2).

A study in the literature reports on a transition scheme tested on 69 patients. According to this scheme, intake of phenprocoumon tablets (3 mg) was stopped and replaced by the same number of warfarin tablets (2.5 mg) day 1-7 after phenprocoumon discontinuation. Thereafter, the dose of warfarin was doubled during day 8-14, and further increased during day 15-18 so that the final dose corresponded to 2.5 times as many warfarin tablets as original phenprocoumon tablets. This scheme was claimed to be optimal for 75 percent of patients and indicated that equipotency was established with a final dose (in mg) of warfarin 2.3 times higher than the original phenprocoumon dose. For the other patients, the dose had to be adjusted individually after measuring the INR. There is a great inter-individual variability in warfarin metabolism, in part related to polymorphic enzymes such as cytochrome P4502C9 (CYP2C9). It is therefore recommended to measure INR every week during five weeks when changing from phenprocoumon to warfarin (2).

Importantly, the issue of over-anticoagulation and risk of bleeding was not properly addressed in this report. Therefore, the perhaps safest alternative would probably be to stop phenprocoumon therapy, and use only dalteparin injections or another LMWH until INR has been normalised, and then initiate warfarin therapy in the accustomed way. Sweetman SC, editor. Martindale, The complete drug reference. 33rd ed. London: Pharmaceutical Press; 2002 Kristiansen C, Lassen JF, Dahler-Eriksen BS, Dahler-Eriksen K et al. Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation. Thromb Res 2000;98:157-63.