How long should the following drugs be stopped prior to knee or hip replacement: raloxifene (Evista), anastrozole (Arimidex), and tamoxifen (Nolvadex, Soltamox)? — Val Cantagallo, MD, Philadelphia, Pa.

All of these drugs affect hormone action, but they have differing clinical uses and risk for embolic events.

Raloxifene and tamoxifen are selective estrogen-receptor modulators, meaning that they affect estrogen action selectively throughout the body. Each drug works a bit differently and therefore they have differing clinical indications. Raloxifene works as an estrogen agonist in bones, reducing bone resorption and fracture risk, and as an estrogen antagonist in the breast and uterus, reducing the risk for breast cancer. Raloxifene is used primarily as a second-line agent for osteoporosis. Similar to raloxifene, tamoxifen works as an estrogen antagonist in breast tissue and bone but as an estrogen agonist in the female lower genital tract. Tamoxifen is used primarily for treatment of breast cancer.

Raloxifene and tamoxifen exert estrogen-like prothrombotic effects, and it is thought that these medications cause reduced antithrombin activity. A large trial of postmenopausal women noted that taking raloxifene caused a hazard ratio of 1.49 for stroke and 1.95 for DVT when compared with placebo (N Engl J Med. 2006;355:125-137, available at www.nejm.org/doi/full/10.1056/NEJMoa062462, accessed November 15, 2013). Tamoxifen has been associated with an increased risk for embolic events, especially in the first two years of treatment and in those undergoing chemotherapy (Lancet. 2002;360:817-824). This increased risk has led to a recommendation to discontinue these drugs 72 hours before prolonged immobilization.

Anastrozole is a selective nonsteroidal aromatase inhibitor that works by blocking the conversion of androstenedione to estrone as well as the conversion of testosterone to estradiol, thus dramatically reducing estrogen levels and exposure to estrogen in hormone-receptive tumors (e.g., estrogen-receptor-positive breast cancer). Since estrogen itself is thought to be a prothrombotic drug, and anoatrozole reduces estrogen levels, there is no increased risk for embolic events with this drug. The primary side effects with anastrozole are decreased bone density (caused by a dramatic drop in sex steroid levels) and elevation of LDL cholesterol. — Kathy Pereira, MSN, FNP-BC, assistant professor, co-coordinator, Family Nurse Practitioner Program, Duke University School of Nursing, Durham, N.C. (182-5)


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