Safety of concomitant tamoxifen and warfarin

To review the literature regarding the potential interaction between tamoxifen and warfarin.

A search of MEDLINE from 1948 to August 20, 2009, was performed using the search terms tamoxifen, warfarin, drug interactions, and cytochrome P450 2C9. EMBASE was searched (1980-week 33, 2009), using the search terms tamoxifen and warfarin, for articles limited to use in humans and published in English, then further narrowed to drug interactions. Bibliographic review was conducted but did not reveal any additional references.

All sources evaluated were published in English and included original case reports, letters, and medical record or database reviews that described an interaction between warfarin and tamoxifen.

Since tamoxifen therapy and cancer increase the risk of venous thromboembolism, warfarin may be prescribed to these patients. However, product information, primary literature, and tertiary literature describe concomitant use of tamoxifen and warfarin as a contraindication since this may increase the level of anticoagulation and the risk of bleeding complications. Although the exact mechanism of the interaction is unknown, one theory is that tamoxifen inhibits CYP2C9, which metabolizes the S-isomer of warfarin. Five publications were identified including 2 letters, 2 individual case reports, and 2 retrospective reviews (1 of the case reports was included in a medical record review). Collectively, these articles described a total of 31 patients taking warfarin and tamoxifen concomitantly, with 8 patients experiencing bleeding complications.

Although concomitant use of warfarin and tamoxifen is deemed a contraindication, evidence regarding this potential interaction is limited. Therefore, safety of concomitant use of tamoxifen and warfarin may be similar to that of other drugs that interact with warfarin, requiring consistent and careful monitoring. However, more evidence is needed to warrant the routine use of this combination.