Drug Breakdown: Tamoxifen

Dr Sharon Rees @reesprescribe

#tamoxifen is a synthetic derivative of estrogen discovered in 1960s. Originally developed as a contraceptive (worked in rats) but had opposite effect in humans, stimulating ovulation! Licensed 1970s as a selective estrogen receptor modulator (SERM) for breast cancer.

Dr Sharon Rees @reesprescribe

Day 2: Main uses for #tamoxifen include estrogen receptor (ER) +ve breast cancer, recurrence and prevention of breast cancer and infertility. Dose usually 20 mg daily, but can increase to 80 mg for anovulatory infertility. Duration of treatment is 5 years for primary prevention breast cancer.

Dr Sharon Rees @reesprescribe

Day 3: #tamoxifen is an oral prodrug with over 99% protein binding. Liver metabolism produces active metabolites and excretion is faecal. CYP3A4 breakdown leads to the metabolite endoxifen and there is further CYP2D6 breakdown to afimoxifene. CYP2D6 polymorphisms and drug inhibitors can alter active drug concentrations. t½ of the main metabolite is 14 days.

Dr Sharon Rees @reesprescribe

Day 4: #tamoxifen is a non-steroidal SERM with complex tissue-dependent binding characteristics. At tumour level, active metabolites block the estrogen receptor (ER) and also cause apoptosis in ER +ve cells. However, agonist activity in the endometrium increases the risk of endometrial cancer, but when acting as an ER agonist in bone tissue, tamoxifen can prevent osteoporosis.