This Wednesday, October 18, 2006, an advisory committee of the US FDA will meet to discuss possible changes in the package insert recommendations for tamoxifen. Currently more than 500,000 post-menopausal women with estrogen receptor positive breast cancer take tamoxifen. Recent pharmacogenetic discoveries suggest that a significant proportion of these women may not be getting the full benefit of tamoxifen either because of their genetic constitution, because of drug interactions, or because of both.

Tamoxifen is a prodrug, meaning that it must be metabolized to an active form—endoxifen—before it can exert its full influence as an estrogen receptor blocker. The enzyme mostly responsible for this metabolic transformation is the 2D6 form of cytochrome P450 (CYP2D6). Perhaps as many as ten-percent of women who take tamoxifen have a form of CYP2D6 that cannot metabolize tamoxifen to endoxifen.

Further, some of the popular selective serotonin uptake inhibitor (SSRI) antidepressants, including Paxil and Prozac, can inhibit the metabolism of tamoxifen by blocking the action of the CYP2D6 enzyme. Many women take both tamoxifen and SSRIs.

If the FDA committee concludes these findings have significant implications for the treatment of breast cancer, the language of the tamoxifen package insert will likely be changed. One consequence will be the more widespread use of genetic testing for forms of the CYP2D6 enzyme. Such tests are already available, though not always covered by health insurance.

Technorati Tags: tamoxifen, CYP2D6, breast cancer, FDA

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