... Is there a problem with the effectiveness of the tamoxifen while taking sertraline (zoloft). Both my physciarist and oncologist states there is no problem. I have noticed an increased shortness of breath and fatigue. Who should I believe? I would like to know what information you have to offer regarding taking both these medications.
Interactions between your selected drugs
tamoxifen ↔ sertraline
Applies to: tamoxifen, Zoloft (sertraline)
GENERALLY AVOID: Chronic coadministration of potent or moderate CYP450 2D6 inhibitors including certain antidepressants may reduce the effectiveness of tamoxifen. The proposed mechanism is inhibition of tamoxifen bioactivation via CYP450 2D6 to endoxifen (4-hydroxy-N-desmethyltamoxifen), the active metabolite that may be responsible for much of tamoxifen's antiestrogenic activity. This is consistent with studies that reported poorer clinical outcome (e.g., increased breast cancer recurrence; shorter relapse-free periods; lower rates of event-free survival) and decreased incidence/severity of hot flashes in patients treated with tamoxifen who have genetic polymorphisms of CYP450 2D6 resulting in reduced or absent enzyme activity. A similar relationship has been observed between endoxifen exposure and alterations in CYP450 2D6 metabolic status, whether due to CYP450 2D6 genetic variants or use of CYP450 2D6 inhibitors such as quinidine or SSRI antidepressants. In a study of 12 patients receiving tamoxifen adjuvant therapy, mean plasma concentrations of endoxifen decreased by more than 50% after four weeks of paroxetine 10 mg/day for hot flashes, and the effect was evident primarily in patients who carried the wild-type genotype for CYP450 2D6 (i.e., extensive metabolizers). In vitro, quinidine reduced the conversion to endoxifen by 79%. Potential clinical implications of this interaction were reported in a retrospective analysis of nearly 1,300 female breast cancer patients who were newly prescribed tamoxifen between 2003 and 2005 and were monitored for at least two years (mean 2.7 years). Women who used a moderate to potent CYP450 2D6 inhibitor (n=353) during tamoxifen therapy had a two-year breast cancer recurrence rate of 13.9%, compared to 7.5% for those not taking any CYP450 2D6 inhibitors (n=945). The average duration of concomitant tamoxifen and CYP450 2D6 inhibitor use was 340 days. In a subset analysis of patients taking tamoxifen with SSRI antidepressants, a breast cancer recurrence rate of 16% was reported for 213 women who used fluoxetine, paroxetine, or sertraline--SSRIs that are considered moderate to potent inhibitors of CYP450 2D6. This rate was 2.2 times higher than that for women taking tamoxifen without CYP450 2D6 inhibitors. In contrast, the breast cancer recurrence rate was 8.8% for 137 women using citalopram, escitalopram, or fluvoxamine, which was not statistically different than controls. An earlier, smaller study conducted by a group of Danish researchers also reported no reduction of tamoxifen effectiveness in association with citalopram or escitalopram use for up to five years. It is important to note that not all studies have found an association between CYP450 2D6 activity and tamoxifen clinical effects. In fact, a couple of studies even reported decreased risk of recurrence in patients treated with tamoxifen who have a common genetic variant of CYP450 2D6. Investigators suggest that the discrepancies may be due to differences in study designs, including sample size, different genetic models for the assessment of phenotypes, and stratification effects.
MANAGEMENT: Based on available data, patients treated with tamoxifen should avoid the chronic use of potent CYP450 2D6 inhibitors such as fluoxetine, paroxetine, and quinidine whenever possible, and preferably also moderate inhibitors such as bupropion, duloxetine, and sertraline. If an antidepressant is required during treatment with tamoxifen, agents such as citalopram, escitalopram, fluvoxamine, mirtazapine, and venlafaxine may be considered, since they have mild to no effects on CYP450 2D6. Alternatively, aromatase inhibitors such as anastrozole, exemestane, and letrozole may be appropriate substitutes for tamoxifen in certain patients.
Other drugs that your selected drugs interact with
tamoxifen interacts with more than 200 other drugs.
Zoloft (sertraline) interacts with more than 300 other drugs.
Interactions between your selected drugs and food
tamoxifen ↔ food
Applies to: tamoxifen
GENERALLY AVOID: Due to their estrogenic effect, isoflavones present in soy such as genistein and daidzein may stimulate breast tumor growth and antagonize the antiproliferative action of tamoxifen and toremifene. Supportive data are derived primarily from in vitro and animal studies. In vitro, low concentrations of these phytoestrogens have been found to promote DNA synthesis and reverse the inhibitory effect of tamoxifen on estrogen-dependent breast cancer cell proliferation. In contrast, high concentrations of genistein greater than 10 microM/L have been found to enhance tamoxifen effects by inhibiting breast cancer cell growth. It is not known if these high concentrations are normally achieved in humans. Plasma concentrations below 4 microM/L have been observed in healthy volunteers given a soy diet for one month or large single doses of genistein. These concentrations are comparable to the low plasma concentrations associated with tumor stimulation reported in animals. In a study of 155 female breast cancer survivors with substantially bothersome hot flashes, a product containing 50 mg of soy isoflavones (40% to 45% genistein; 40% to 45% daidzein; 10% to 20% glycitein) taken three times a day was found to be no more effective than placebo in reducing hot flashes. No toxicity or recurrence of breast cancer was reported during the 9-week study period.
MANAGEMENT: Until more information is available, patients treated with tamoxifen or toremifene may consider avoiding the consumption of soy-containing products.
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