An excerpt from a Medscape CME article on this new report states:
" New recommendations extend previous work that singled out paroxetine and fluoxetine as drugs to avoid in women who are already taking tamoxifen, as reported by Medscape Oncology, and they include certain antipsychotics, cardiac drugs, and medications for infectious diseases.
Which medications should be avoided in the setting of tamoxifen? This important clinical question is asked by physicians and patients on a daily basis in clinical practice, say the authors of the review. They are all from the Mayo Clinic, in Rochester, Minnesota; the senior author is Matthew Goetz, MD.
This team has been at the forefront of research into tamoxifen metabolism, which occurs in the cytochrome P450 system, primarily by the rate-limiting enzyme CYP2D6. It is clinically important because the drug exerts its beneficial effects through its active metabolite (endoxifen), and any interference with the metabolism of tamoxifen leads to lower blood levels and less protection against breast cancer.
Previously, this team used CYP2DP genotyping to identify poor and good metabolizers of tamoxifen, who respond, correspondingly, either poorly or well to treatment with tamoxifen, as previously reported by Medscape Oncology
Medications to Avoid
Now the team has reviewed the medical literature for evidence of drugs that are strong inhibitors of CYP2D6; these should not be prescribed with tamoxifen because they interfere with its metabolism and result in lower blood levels of the active metabolite.
"We recommend that potent CYP2D6 inhibitors be avoided in women receiving tamoxifen," the authors state, adding that there is "strong" evidence to support this recommendation.
The authors list the following drugs as moderate to potent inhibitors of CYP2D6:
- antidepressants that act as selective serotonin reuptake inhibitors (SSRIs) or selective noradrenergic reuptake inhibitors (SNRIs) — paroxetine, fluoxetine, bupropion, and duloxetine
- antipsychotics — thioridazine, perphenazine, and pimozide
- cardiac drugs — quinidine and ticlopidine
- medications for infectious disease — terfenadine and quinidine
- miscellaneous medication — cinacalcet."
J Clin Oncol. 2010 Jun 1;28(16):2768-76. Epub 2010 May 3.
Coprescription of tamoxifen and medications that inhibit CYP2D6.Sideras K, Ingle JN, Ames MM, Loprinzi CL, Mrazek DP, Black JL, Weinshilboum RM, Hawse JR, Spelsberg TC, Goetz MP.Department of Oncology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
Abstract: Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.PMID: 20439629 [PubMed - in process]