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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EFor patients with comorbid medical conditions, knowledge of drug metabolism is important and may in fact be critical in the oncology setting. A case in point is the widespread use of the anti-estrogen compound tamoxifen, which acts via estrogen receptor modulation. Unfortunately, one of the more common adverse events that occur with this drug is hot flashes, a condition that is uncomfortable to the point of discouraging long-term treatment adherence. An attempt to resolve this discomfort may result in additional unforeseen risk.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emood disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ebreast cancer\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EFor patients with comorbid medical conditions, knowledge of drug metabolism is important and may in fact be critical in the oncology setting. \u201cAs physicians, we need to know everything about our patients that we can,\u201d said David Flockhart, MD, PhD, Indiana University School of Medicine, Indianapolis, IN. At the very least, it is important to know what medications they are currently taking.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EA case in point is the widespread use of the anti-estrogen compound tamoxifen, which acts via estrogen receptor (ER) modulation. Tamoxifen is highly effective in the prevention of breast cancer in ER-positive women and is used both as adjuvant therapy against cancer recurrence and as a prevention measure for those who are considered to be at high risk for disease. Unfortunately, one of the more common adverse events that occur with this drug is hot flashes, a condition that is uncomfortable to the point of discouraging long-term treatment adherence. An attempt to resolve this discomfort may result in additional unforeseen risk.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ETo illustrate this point, Dr. Flockhart presented a case report of a 45-year-old woman with tamoxifen-related hot flashes and comorbid depression who was prescribed paroxetine. Within a week, the hot flashes resolved; the hot flashes resumed when she was taken off paroxetine. \u201cNow, paroxetine\u0027s effect on depression takes much longer than a week, so there\u0027s something else going on here.\u201d The working hypothesis was that paroxetine had somehow interfered with the anti-estrogen activity of tamoxifen, either by preventing absorption, which seemed unlikely, or by altering the transformation of tamoxifen into its active metabolite, endoxifen. \u201cWe were lucky to have chromatograms of this woman before and after peroxetine administration,\u201d said Dr. Flockhart, and analysis of these data showed an obvious decrease in endoxifen concentrations. \u201cWe were very interested in this. There is some sort of decreased activity in this woman when she\u0027s taking paroxetine.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003ECytochrome P450 enzyme activity was the most likely suspect\u2014specifically, subtype CYP2D6, a site of metabolism for multiple commonly prescribed drugs. Prior investigations confirm that paroxetine inhibits this enzyme, but the extent and therapeutic impact of inhibition are unclear. In a small study of 12 women with tamoxifen-induced hot flashes, Dr. Flockhart, using a combination of serum concentration and genetic analysis, was able to determine that the effect of paroxetine\/CYP2D6 downregulation was so pronounced, it nearly matched the lack of activity seen in women who had a mutant, non-functioning form of the enzyme [\u003Cem\u003EJ Natl Cancer Inst\u003C\/em\u003E 2003].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThis observation was cause for great concern. An estimated 30% of tamoxifen-treated patients are prescribed antidepressants for depression or hot flashes. Were other SSRIs placing them at risk? One answer came from Jin et al, who investigated the plasma concentrations of endoxifen in patients who were concomitantly using one of 3 different SSRIs. Inhibition of the CYP2D6 enzyme was determined and ranked as follows: paroxetine \u0026gt; sertraline \u0026gt; venlafaxine [\u003Cem\u003EJ Natl Cancer Inst\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ECommenting on these results, Dr. Flockhart noted that venlafaxine can be effectively used to treat tamoxifen-related hot flashes while retaining tamoxifen protection. \u201cThis can improve compliance with this very effective medication\u201d and thereby have a direct impact on long-term survival. Other investigators have carried these observations forward, and there is now consensus that the following agents are potent inhibitors of CYP2D6 and should not be prescribed with tamoxifen: bupropion, fluoxetine, and paroxetine (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigures 1\u003C\/a\u003E and \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003E2\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Partial List of Common CYP2D6 Inhibitors.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1823296912\u0022 data-figure-caption=\u0022Partial List of Common CYP2D6 Inhibitors.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10910\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EPartial List of Common CYP2D6 Inhibitors.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Inhibition of CYP2D6 Affects Endoxifen Concentrations.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1823296912\u0022 data-figure-caption=\u0022Inhibition of CYP2D6 Affects Endoxifen Concentrations.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/26\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10913\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EInhibition of CYP2D6 Affects Endoxifen Concentrations.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/3\/26.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 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