Product Information
Registration Status: ActiveNOLVADEX TABLET 10mg is approved to be sold in Singapore with effective from 1988-06-05. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN00794P.
This product contains Tamoxifen 10mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by ASTRAZENECA UK LTD in UNITED KINGDOM.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
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.
Indication
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.
Pharmacokinetics
- Absorption
- 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.
- Distribution
- Metabolism
- 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.
- Elimination
Clearance
Clearance (CL/F) as body weight adjusted in female pediatric patients was approximately 2.3-fold higher than in female breast cancer patients.
Toxicity
Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
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 |
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.