Can the drug paroxetine mesylate (Brisdelle, Paxil) be given to patients taking a chemoprevention drug such as raloxifene (Evista) or any of the aromatase inhibitors? I have read research on tamoxifen and paroxetine, but not seen any research on the other chemoprevention drugs.  
—Maggie Siebeneichen, RN, BSN, BA

Tamoxifen and raloxifene (Evista) are FDA-approved for the prevention of breast cancer in women at increased risk of breast cancer.1 Tamoxifen and the aromatase inhibitors (exemestane [Aromasin, generic], anastrozole [Arimidex, generics], letrozole [Femara, generics]) are used in the adjuvant therapy of women with ER/PR positive breast cancer.2 Women receiving treatment with these agents may experience hot flushes and other menopausal symptoms.3 Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that may be used to treat hot flushes and depression. Paroxetine also inhibits cytochrome P-450 (CYP) 2D6, the enzyme responsible for converting tamoxifen to its active metabolites. Because this may reduce the efficacy of tamoxifen, concomitant use of tamoxifen with paroxetine and fluoxetine (Prozac) should be avoided.2 Other therapies (eg, venlafaxine [Effexor]) are preferred as they have less impact on tamoxifen metabolism.

Raloxifene and the aromatase inhibitors are not significantly impacted by CYP2D6 inhibitors and inducers, but may have interactions with other medications due to how they are metabolized. For example, exemestane is metabolized by CYP3A4 and co-administration of 3A4 inducers (eg, carbamazepine [Tegretol], St John’s wort) may reduce its exposure and efficacy. Therefore, recommendations are to either avoid this combination or to adjust the dose of exemestane in patients receiving a strong CYP3A4 inducer.


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An important note is that drug-drug interactions may be caused by mechanisms other than CYP enzymes; for instance, raloxifene may affect the binding of other drugs such as warfarin (Coumadin) and diazepam (Valium) and impact the effects of these medications. Due to the variety of drug-drug interactions that may occur, a pharmacist review of the complete list of the patient’s medications and any vitamins or supplements is essential to identify interactions with these treatments.

 

REFERENCES

1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer Risk Reduction. Version 1.2013. National Comprehensive Cancer Network Web site. http://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf. Accessed November 11, 2013.

2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Breast Cancer. Version 3.2013. National Comprehensive Cancer Network Web site. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed November 11, 2013.

3. Thompson LA. Hot flushes on tamoxifen [Ask A Pharmacist]. Oncol Nurse Advisor. 2011;2(2):48. https://www.oncologynurseadvisor.com/home/departments/ask-a-pharmacist/hot-flushes-on-tamoxifen/. Accessed November 11, 2013.