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Prescriber Update Articles

Tamoxifen: CYP2D6 interactions and variable clinical response

Web site: June 2011
Prescriber Update 2011;32(2):10

Recent evidence suggests there is a potential risk for higher rates of disease recurrence and death related to breast cancer in women taking tamoxifen concomitantly with CYP2D6 inihibitors. It is noted in the literature that CYP2D6 inhibitors such as selective serotonin reuptake inhibitors (SSRIs) are commonly used concomitantly with tamoxifen.

The interaction centers on endoxifen. Endoxifen is an important active metabolite that contributes significantly to the efficacy of tamoxifen and is produced by the metabolism of tamoxifen via CYP2D6. Drugs that inhibit CYP2D6 can therefore lead to reduced plasma concentrations of endoxifen and reduced action.

A study1 involving over 1,200 women found that the 2-year breast cancer recurrence rate was 1.9 times higher in patients receiving both tamoxifen and a CYP2D6 inhibitor, compared to those receiving tamoxifen only (13.9% vs 7.5%). In addition the breast cancer recurrence rate was 2.2 times higher in women receiving a moderate to potent CYP2D6 inhibitor.

A more recent population based cohort study2 (n=2430) found an increased risk of death related to breast cancer in women taking tamoxifen and concomitant paroxetine. A dose response relationship was apparent, with relative increases in death related to breast cancer associated with increased time of overlapping tamoxifen and paroxetine treatment. The authors estimated that overlapping treatment with paroxetine for 41% of tamoxifen therapy (the median in the study) could result in one additional breast cancer death at five years for every 20 women who need both medicines. An association did not extend to other SSRIs in this study such as citalopram, escitalopram, sertraline, mirtazapine and venlafaxine.

Advice for prescribers:

Further information about this interaction is available in two recently published reviews.3,4

Medsafe is currently working with manufacturers to provide more information about this interaction in applicable medicine data sheets.

References

  1. Medco Health Solutions Inc., and the Indiana University School of Medicine (2009) Increased risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors. Presentation at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting.
  2. Kelly CM, Juurlink DN, Gomes T, et al (2010) Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. British Medical Journal. 340:693.
  3. Desmarais, JE, and Looper KJ (2009) Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. Journal of Clinical Psychiatry. 70(12):1688-1697.
  4. Henry NL, Stearns V, Flockhart DA, et al (2008) Drug interactions and pharmacogenomics in the treatment of breast cancer and depression. American Journal of Psychiatry. 165(10):1251-1255.