Tamoxifen Citrate Tablets

Overview of Tamoxifen Citrate Tablets

Dosage Strength

10 mg
20 mg

General Information

Selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic actions on diverse tissues, have their prototype medication in the form of tamoxifen. Diethylstilbestrol and tamoxifen share the same nucleus, but tamoxifen has an extra side chain (trans isomer) that gives it antiestrogenic action. It shares a molecular bond with the antiestrogen clomiphene. Both males and postmenopausal women who have metastatic estrogen receptor (ER) positive breast cancer are treated with tamoxifen as the main hormonal therapy. In women of all ages, adjuvant tamoxifen medication greatly lowers the risk of breast cancer death and recurrence. When tamoxifen is administered to women with ER-positive malignancies for 5 years as opposed to 1–3 years, the benefit is larger. 1 In women who are at high risk for the disease, tamoxifen has been demonstrated to reduce the incidence of ER-positive breast cancer. On the emergence of ER-negative illness, it has little impact. 2 The Study of Tamoxifen and Raloxifene, or STAR, is a new study that is comparing the advantages of raloxifene and tamoxifen in the prevention of breast cancer. Preliminary findings show that raloxifene similarly lowers breast cancer risk. The combination therapy arm of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, which compared tamoxifen or anastrozole to the combination of anastrozole and tamoxifen in postmenopausal women with early breast cancer, was terminated early because an efficacy benefit over tamoxifen therapy alone could not be proven. In addition, compared to tamoxifen therapy, anastrozole monotherapy was linked to a higher survival benefit after a median of 5 years (hazard ratio 0.87, 95 percent confidence interval 0.78—0.97, p=0.0127). The incidence of vaginal symptoms, thromboembolic events, stroke, and endometrial malignancy was higher in the tamoxifen-only group of patients. Patients using anastrozole, however, had a higher risk of fractures (including fractures of the spine, hip, or wrist), joint conditions (such as arthralgia, arthritis), and hypercholesterolemia. When exemestane and letrozole were evaluated against tamoxifen in postmenopausal women with early breast cancer, similar results were seen. In 1977, the FDA initially gave tamoxifen its approval. On October 29, 2005, the FDA gave its approval to an oral treatment (SoltamoxTM). For certain women, a MedGuide is available for tamoxifen and must be provided with each new prescription and refill. The use of tamoxifen to reduce the risk of breast cancer in high-risk women and in patients being treated for ductal carcinoma in situ (DCIS) is the ONLY use covered by the MedGuide, both of which call for careful consideration of the drug’s risks and rewards. The Endocrinologic and Metabolic Drugs FDA Advisory Committee recommended in October 2006 that the prescribing information for tamoxifen be updated to reflect the possibility that patients with slow CYP2D6 metabolism may have an increased risk of breast cancer recurrence. It is unclear, however, whether testing for slow CYP2D6 metabolism will be necessary for proper prescribing.

References

1.Early Breast Cancer Trialists’ Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 1998;16:1451-67.
2.Fisher B, Costantino JP, Wickerman L, et al. Tamoxifen for the prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371-88.
3.Khalkhali-Ellis Z, Christian AL, Kirschmann DA, et al. Regulating the tumor suppressor gene maspin in breast cancer cells. Clinical Cancer Research 2004;10:449-54.
4.Desta Z, Ward BA, Soukhova NV, et al. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6.
5.Kiyotani K, Mushiroda T, Imamura CK, et al. Significant effects of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. J Clin Oncol 2010;28:1287-1293.
6.Wu X, Hawse JR, Subramaniam M, et al. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res 2009;69:1722-1727.
7.Sideras K, Ingle JN, Ames MM, et al. Coprescription of tamoxifen and medications that inhibit CYP2D6. J Clin Oncol 2010;28:2768-2776.
8.Schroth W, Goetz MP, Hamann U, et al. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA. 2009;302:1429-1436
9.Nolvadex (tamoxifen) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2006 Mar
10.Zhao XJ, Jones DR, Wang YH, et al. Reversible and irreversible inhibition of CYP3A enzymes by tamoxifen and metabolites. Xenobiotica 2002;32:863-78.
11.Crewe HK, Notley LM, Wunsch RM, et al. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4’-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos 2002;30:869-74
12.Kinsinger LS, Harris R, Woolf SH, et al. Chemoprevention of breast cancer: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:59-67.
13.Tewari K, Bonebrake RG, Asrat T, et al. Ambiguous genitalia in an infant exposed to tamoxifen in utero. Lancet 1997;350:183.
14.Tamoxifen package insert. Sellersville, PA: Teva Pharmaceuticals USA; 2008 Aug.
15.Shaaban MM. Suppression of lactation by an antiestrogen, tamoxifen. Eur J Obstet Gynecol Reprod Biol 1975;4:167-9.
16.Tamoxifen tablets package insert. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2013 Apr.
17.Litovitz TL, Klein-Schwartz W, Oderda GM, et al. Ipecac administration in children younger than 1 year of age. Pediatrics 1985;76(5):761-764.

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