Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.
Active Ingredient / Synonyms
(Z)-2-(4-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylethanamine | (Z)-2-(para-(1,2-Diphenyl-1-butenyl)phenoxy)-N,N-dimethylamine | 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene | 1-para-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene | Tamoxifen | Tamoxifène | Tamoxifene | Tamoxifeno | Tamoxifenum | trans-Tamoxifen | Tamoxifen |
One of the selective estrogen receptor modulators (SERM) with tissue-specific activities for the treatment and prevention of estrogen receptor positive breast cancer. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium.
Tamoxifen is indicated for the treatment of metastatic breast cancer in women and men and ductal carcinoma in Situ.
Mechanism of Action
Tamoxifen is a nonsteroidal agent that 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.
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.
When a single oral dose of 20 mg is given, the average peak plasma concentration (Cmax) is 40 ng/mL which occurred approximately 5 hours after dosing (Tmax). The Cmax of N-desmethyl tamoxifen is 15 ng/mL. Steady-state concentrations for tamoxifen is achieved in 4 weeks, while steady-state concentrations for N-desmethyl tamoxifen is achieved in 8 weeks.
Hepatic. Tamoxifen is extensively metabolized after oral administration. N-Desmethyl-tamoxifen is the major metabolite found in plasma. N-Desmethyl-tamoxifen's activity is similar to tamoxifen. 4-hydroxy-tamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. 4-Hydroxy-tamoxifen formation is catalyzed mainly by cytochrome P450 (CYP) 2D6, and also by CYP2C9 and 3A4. At high tamoxifen concentrations, CYP2B6 also catalyzes 4-hydroxylation of the parent drug. 4-Hydroxy-tamoxifen possesses 30- to 100-times greater affinity for the estrogen receptor and 30- to 100-times greater potency at inhibiting estrogen-dependent cell proliferation compared to tamoxifen. It is also metabolized by flavin monooxygenases FMO1 and FMO3 to form tamoxifen-N-oxide.
65% of the dose was excreted from the body over 2 weeks in which fecal excretion was the primary route of elimination. Tamoxifen is excreted mainly as polar conjugates, with unchanged drug and unconjugated metabolites accounting for less than 30% of the total fecal radioactivity.
The decline in tamoxifen plasma concentrations is biphasic with a terminal elimination half-life of approximately 5 to 7 days. The estimated half-life of N-desmethyl tamoxifen is 14 days.
Clearance (CL/F) as body weight adjusted in female pediatric patients was approximately 2.3-fold higher than in female breast cancer patients.
Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
Although best effort has been made to ensure the information provided is correct and updated, users are advised to visit HSA Official website whenever in doubt. Please see Disclaimers.
We welcome all the content error reporting/feedback. Please contact us @ Text Us!