Tamoxifen

(tamoxifen citrate)

Brands

Apo-Tamox, Nolvadex, Tamofen, Tamone

Availability

Tablets: 10 mg & 20 mg

Pharmacology

Tamoxifen, a selective estrogen receptor modulator (SERM) is an antineoplastic, nonsteroidal agent. It is an oral hormone that has potent antiestrogenic properties. The exact mechanism of action is unknown. It is believed to compete with estrogen by binding to estrogen receptors on breast cancer cells thus preventing endogenous estrogens from stimulating tumor growth. It is also able to block the uptake of estradiol.

Tamoxifen is primarily used in humans as an adjuvant therapy in node-negative or node-positive breast cancer. It is used in premenopausal women as an alternative to oophorectomy or radiation with estrogen positive tumors. It is also used in men with advanced breast cancer.

Tamoxifen is considered investigational in its use in mastalgia, pancreatic carcinoma, advanced and recurrent endometrial and hepatocellular carcinoma.

An oral agent that is well absorbed from the GI tract, tamoxifen is extensively metabolized in the liver to several metabolites, and is excreted primarily in the feces. It is also excreted in breast milk.

Indications

Used in rats as palliative or adjuvant treatment in malignant mammary tumors, and pituitary tumors sensitive to estrogen.

Drug Interactions or Contraindications

If used with other cytotoxic drugs increases risk of thromboembolic events.

Adverse Reactions

CNS: poor coordination, fatigue

CV: thrombolytic disorders, pulmonary embolism, peripheral edema

GI: anorexia, diarrhea, abdominal pain

GU: vaginal bleeding, ovarian cysts, hyperplasia of uterus, uterine cancer

Other: hepatic necrosis, weight gain or loss, increased bone pain, pain from tumor, thinning or loss of hair/fur

Dosage Recommendations

*Note: Dosages in rats are empirical.*

1.5 mg/lb to 3 mg/lb, PO, SID ³^, ¹²

or

6.6 mg/kg, SID, for 6 days on, with one day off each week in existing tumors. ¹²

or

3.3 mg/kg, SID, for 6 days on, with one day off each week as a preventative measure. ¹²

*Note: Plasma and or Steady-state levels may take several weeks to attain, and objective response may be delayed if metastasis has occurred. May be combined with melatonin to enhance or boost protective effect of tamoxifen ¹.

Considerations

Observed respiratory difficulties and convulsions in animals at high doses.
Stop drug 2 weeks prior to any surgical procedures (to prevent increased bleeding time).
Do not give to pregnant animals.
Administer an analgesic if pain increases.
Encourage fluids to prevent hypercalcemia.
Recommended to wear disposable gloves when cleaning cage of urine and feces and place in closed plastic bag for disposal.
Read manufacturers label for storing.

References

Kothari, A., Borges, A., Ingle, A., & Kothari, L. (1997). Combination of melatonin and tamoxifen as a chemoprophylaxis against N-nitroso-N-methylurea-induced rat mammary tumors. Cancer Letters, 111(1-2), 59-66. Retrieved August 14, 2020, from https://www.sciencedirect.com/science/article/abs/pii/S030438359604493X . doi:10.1016/s0304-3835(96)04493-x