Brands, Medical Use, Clinical Data
Brands / Synonyms
Apo-Tamox; Citofen; Crisafeno; CTX; Diemon; Gen-Tamoxifen; Istubol; Kessar; Noltam; Nolvadex; Nolvadex-D; Nourytam; Novo-Tamoxifen; Oncomox; Pms-Tamoxifen; Retaxim; Soltamox; Tamizam; Tamofen; Tamone; Tamoxasta; Tamoxen; Tamoxifen and Its Salts; Tamoxifen Citrate; Tamoxifen Drug Standard Solution; Tamoxifene [Inn-French]; Tamoxifeno [Inn-Spanish]; Tamoxifenum [Inn-Latin]; TRANS FORM OF TAMOXIFEN; Trans-Tamoxifen; Valodex; Zemide
for the treatment of breast cancer
Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity. Tamoxifen, chemically related to clomiphene., is used to in the therapy of metastatic breast cancer.
Mechanism of Action
Tamoxifen binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
Biotrnasformation / Drug Metabolism
NOLVADEX is contraindicated in patients with known hypersensitivity to the drug or any of its ingredients.
Reduction in Breast Cancer Incidence in High Risk Women and Women with DCIS:
NOLVADEX is contraindicated in women who require concomitant coumarin-type anticoagulant therapy or in women with
a history of deep vein thrombosis or pulmonary embolus.
When NOLVADEX is used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant
effect may occur. Where such coadministration exists, careful monitoring of the patientís prothrombin time is
In the NSABP P-1 trial, women who required coumarin-type anticoagulants for any reason were ineligible for
participation in the trial.
There is an increased risk of thromboembolic events occurring when cytotoxic agents are used in combination with
Tamoxifen reduced letrozole plasma concentrations by 37%. The effect of tamoxifen on metabolism and excretion of
other antineoplastic drugs, such as cyclophosphamide and other drugs that require mixed function oxidases for
activation, is not known. Tamoxifen and N-desmethyl tamoxifen plasma concentrations have been shown to be reduced
when coadministered with rifampin or aminoglutethimide. Induction of CYP3A4-mediated metabolism is considered to be
the mechanism by which these reductions occur; other CYP3A4 inducing agents have not been studied to confirm this
One patient receiving NOLVADEX with concomitant phenobarbital exhibited a steady state serum level of tamoxifen
lower than that observed for other patients (ie, 26 ng/mL vs. mean value of 122 ng/mL). However, the clinical
significance of this finding is not known. Rifampin induced the metabolism of tamoxifen and significantly reduced the
plasma concentrations of tamoxifen in 10 patients. Aminoglutethimide reduces tamoxifen and N desmethyl tamoxifen
plasma concentrations. Medroxyprogesterone reduces plasma concentrations of N-desmethyl, but not tamoxifen.
Concomitant bromocriptine therapy has been shown to elevate serum tamoxifen and N-desmethyl tamoxifen.
Drug/Laboratory Testing Interactions:
During postmarketing surveillance, T4 elevations were reported for a few postmenopausal patients which may be
explained by increases in thyroid-binding globulin. These elevations were not accompanied by clinical
Variations in the karyopyknotic index on vaginal smears and various degrees of estrogen effect on Pap smears have
been infrequently seen in postmenopausal patients given NOLVADEX.
In the postmarketing experience with NOLVADEX, infrequent cases of hyperlipidemias have been reported. Periodic
monitoring of plasma triglycerides and cholesterol may be indicated in patients with pre-existing hyperlipidemias