Question of the Week # 135

Q135) A 45 year old woman was recently diagnosed with Stage II right sided breast cancer with positive axillary lymphnodes. The tumor was positive for estrogen receptors. She received lumpectomy followed by chemotherapy and then, radiation. She is then placed on Tamoxifen three weeks ago. The patient has been experiencing severe hot flashes since the start of Tamoxifen therapy. Most important next step in management:

A) Discontinue Tamoxifen

B) Start Fluoxetine

C) Start Venlafaxine

D) Start low dose estrogen pills

E) Reassure that symptoms will abate

7 Responses

  1. c

  2. c….fluoxetine and Tamoxifene have drug interaction and the former reduces or abolishes the protective effect of later

  3. c

  4. c

    Certain drugs, including several commonly prescribed antidepressants (those in the category called selective serotonin reuptake inhibitors, or SSRIs), inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the use of tamoxifen by the body because it metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.

    The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its potency is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.

    Researchers have found that women taking certain SSRIs together with tamoxifen have decreased blood levels of active tamoxifen metabolites. Because of this, many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors. For example, doctors may recommend switching from an SSRI that is a potent inhibitor of CYP2D6 (such as paroxetine) to one that is a weaker inhibitor (such as sertraline) or that has no inhibitory activity (such as venlafaxine or citalopram), or they may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.

    Other medications that inhibit CYP2D6 include the following:

    Quinidine, which is used to treat abnormal heart rhythms
    Diphenhydramine, which is an antihistamine
    Cimetidine, which is used to reduce stomach acid

  5. E.this women is not on any SSRI first and hot flashes is common side effect of tamoxifen so I would go with d although e also looks reasonable but as q is saying severe hot flashes.
    Dr.Red please explain

  6. C. Note: Fluoxetine is a potent inhibitor of endoxifen, active tamoxifene metabolite, and significantly reduces hot flashes. Although venlafaxine reduces hot flashes as well, the potency is much lower. So in order not to curtail the beneficial anti-cancer effect of tamoxifen, better to use venlafaxine.

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