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.
Dr Sharon Rees @reesprescribe
Day 4 (cont): #tamoxifen resistance is intrinsic to a high percentage of advanced breast cancer cases and in 30-40% resistance can be acquired. Theories include altered estrogen receptor signaling, down-regulation of the estrogen receptor, or functional variations in the tamoxifen-ER complex, affecting gene regulation.
Dr Sharon Rees @reesprescribe
Day 5: Common adverse drug reactions for #tamoxifen include alopecia, constipation, hot flush, fatigue, nausea, rash. Serious or rare; endometrial cancer, increased risk VTE, agranulocytosis, ocular toxicity. Long-term therapy can lead to hepatotoxicity (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 6: #tamoxifen has severe drug-drug interactions with CYP2D6 inhibitors, which lead to reduced efficacy eg paroxetine, fluoxetine, cinacalcet, terbinafine. #tamoxifen also increases the effect of warfarin possibly by reducing CYP2C9 activity. Multiple moderate drug-drug interactions (DDIs) (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 7: Interesting fact; some foods and herbs could alter efficacy eg oranges/citrus fruits which contain tangeretin (mainly peel) and grapefruit (CYP3A4 inhibitor) can all reduce efficacy of #tamoxifen. Valerian and turmeric may inhibit breakdown too (the PIL just refers to ‘herbs’).
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
Complete the additional reading suggested below and then answer the ten questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Tamoxifen is a naturally occurring form of estrogen?
TRUE or FALSE?
Which is TRUE?
- Tamoxifen is a pro-drug
- Tamoxifen was originally developed to prevent hot flushes
- Tamoxifen was licensed for use in the USA in the 1960s
- The main indication for use is polycystic ovarian syndrome
Tamoxifen is usually given for a duration of 10 years for primary prevention of breast cancer
TRUE or FALSE
Tamoxifen is only helpful if the type of breast cancer is estrogen receptor positive
TRUE or FALSE
Which is TRUE?
- Tamoxifen has a very short half-life
- 80mg is the standard dose for breast cancer
- More than one CYP450 enzyme family is needed to release the active metabolites
- There is no resistance to tamoxifen
Tamoxifen acts purely as an antagonist at the estrogen receptor in all tissues
TRUE or FALSE?
Which is NOT a common adverse drug reaction?
- Fatigue
- Nausea
- Constipation
- Ocular toxicity
CYP2D6 inhibitors such as paroxetine and terbinafine can reduce the efficacy of tamoxifen
TRUE or FALSE?
Long-term therapy with tamoxifen can cause cancers and liver disease
TRUE or FALSE?
The DDI between tamoxifen and warfarin is classified as moderate
TRUE or FALSE?
Further reading on #tamoxifen
- Breast cancer: https://bnf.nice.org.uk/treatment-summary/breast-cancer.html
- Tamoxifen: https://bnf.nice.org.uk/drug/tamoxifen.html#drugAction
- Tamoxifen 20mg Film-Coated Tablets: https://www.medicines.org.uk/emc/product/2248/smpc#PRODUCTINFO