Окт
12
12-10-2009

The anticoagulant effects of warfarin are markedly increased by Nolvadex. A dosage reduction (about a half, or even more) may be needed to avoid bleeding.

Clinical evidence
A woman on warfarin needed a dosage reduction from five to 1 mg daily to keep her prothrombin time within the range 20-25 s while taking 40 mg Nolvadex daily. A retrospective study of the records of five other patients on Nolvadex revealed that two had shown marked increases in prothrombin times and bleeding shortly after starting warfarin. The other three needed warfarin doses which were about one-third of those taken by other patients not on Nolvadex.

This confirms the first report of this interaction in a woman on warfarin who developed haematemesis, abdominal pain and haematuna six weeks after starting 20 mg Nolvadex daily. Her prothrombin time had risen from 39 to 206. She was restabilized on a little over half the warfarin dosage while continuing to take the Nolvadex. The Aberdeen Hospitals Drug File has on record 22 patients given both drugs 17 of them had no problems but two developed grossly elevated warfarin levels and three haemorrhaged. The manufacturers (ICI) of Nolvadex have another report of this interaction on their files.

Mechanism
Uncertain it seems possible that these drugs compete for the same metabolizing systems in the liver, the result being that the loss of the warfarin is reduced and its effects increased and prolonged.

Importance and management
An established and clinically important interaction Monitor the effects closely if Nolvadex is added to treatment with warfarin and reduce the dosage appropriately The reports cited indicate a reduction of a half to two-thirds Some may need much larger reductions The warfarin dosage will need to be increased if the Nolvadex is later withdrawn The authors of one of the reports postulate that the anti-tumour effects of the Nolvadex may also possibly be reduced This needs further study. The effect of Nolvadex on other anticoagulants is uncertain but be alert for the same reaction.