Tamoxifen and CYP2D6 Inhibitors

Tamoxifen and CYP2D6 Inhibitors

Two papers presented at the recent American Society of Clinical Oncology (ASCO) have brought to light to potential serious drug interaction between tamoxifen and several commonly used SSRI antidepressants. Tamoxifen is an estrogen receptor blocker commonly used in patients with hormone receptor-positive breast cancer. Many women taking tamoxifen are also taking SSRIs for the treatment of hot flashes or depression. Tamoxifen is extensively metabolized by cytochrome P450 enzymes to its active metabolites, which are primarily responsible for many effects of the drug. Some SSRIs, particularly paroxetine and fluoxetine, are potent inhibitors of CYP2D6, the main enzyme responsible for conversion of tamoxifen to its active form. The studies presented at ASCO revealed some conflicting results, but at least one suggested a near doubling of breast cancer recurrence when tamoxifen was administered with a CYP2D6 inhibitor, findings that agree with some previous studies.

Experts who discussed these findings at ASCO are now generally advising patients who are taking tamoxifen to avoid strong CYP2D6 inhibitors including paroxetine, fluoxetine, sertraline, and even drugs such as bupropion and duloxetine. Options for women taking tamoxifen include citalopram, escitalopram, fluvoxamine, mirtazapine, nefazodone, and venlafaxine. Alternatively, postmenopausal women can be treated with an aromatase inhibitor rather than tamoxifen, as these drugs are not affected by CYP2D6 (J Clin Oncol 2009;27(15S):Abstract CRA 508; J Clin Oncol 2009;27(15S):Abstract CRA 509).