Tamoxifen and venous thromboembolism

The International Breast Cancer Intervention Study (1), which investigated the use of tamoxifen in the unlicensed indication of breast cancer prevention, revealed that women treated with tamoxifen had an approximately 2.3x increased risk of venous thromboembolism (VTE) than those treated with placebo. Approximately 40% of the VTE cases occurred within 3 months of surgery or following immobility. This led to the Chairman of the study, in March 2002, recommending that women should no longer be treated with tamoxifen for the PREVENTION of breast cancer (i.e. prevention of occurrence rather than management of diagnosed disease).

The Committee on Safety of Medicines has recommended that (1):

• For breast cancer treatment
  • Prior to starting treatment with tamoxifen
    • obtain a careful personal and family history of VTE
    • the decision to treat should be based on the overall risk to the patient
    • use of prophylactic anticoagulant may be justified
  • Surgery/immobility
    • do not stop tamoxifen therapy before surgery or long-term immobility unless the risk of tamoxifen-induced VTE clearly outweighs the risk of interrupting treatment
    • the decision should take into account the possible duration of treatment interruption, the stage and grade of cancer, the clinical response of the patient to tamoxifen and the stage of the treatment regimen at which the interruption occurs
    • all patients should receive appropriate thrombosis prophylactic measures
  • Occurence of VTE
    • stop tamoxifen immediately and initiate anti-thrombosis measures
    • the decision to restart tamoxifen should be taken with respect to the overall risk: benefit balance for the patient
    • anticoagulation measures should be considered if the patient is restarted on tamoxifen
• For anovulatory infertility
  • Prior to starting treatment with tamoxifen
    • tamoxifen is contraindicated in patients with known personal or family history of confirmed, idiopathic VTE or known genetic defect that predisposes to thrombophilia
  • Surgery/immobility
    • stop tamoxifen therapy at least 6 weeks before surgery or long-term immobility and recommence only when the patient is fully mobile
    • all patients should receive appropriate thrombosis prophylactic measures
  • Occurence of VTE
    • stop tamoxifen immediately and initate appropriate anti-thrombotic measures
    • do not recommence tamoxifen unlsess there is a compelling alternative explanation for the thrombotic event

Reference:

1. Current Problems in Pharmacovigilance (2002), 28, 10.