EpistemisOncological hormone therapy and hormonal antagonists
Therapies designed to suppress the proliferation of sex steroid-dependent tumors by blocking their membrane receptors or selectively inactivating their systemic synthesis.
File
Tamoxifen Nolvadex, Are TAMPharmacological Group: Selective estrogen receptor modulator (SERM), hormone therapy.
Mechanism of Action: It is a non-steroidal prodrug that undergoes hepatic hydroxylation by CYP2D6 to generate its metabolites with much higher therapeutic affinity, endoxifen and 4-hydroxytamoxifen. It exerts a dual target tissue-dependent activity (SERM): it acts as a competitive antagonist of estrogen in breast tissue, blocking the transcription of growth factors and arresting estrogen-dependent breast cancer cells in the G1 phase. Simultaneously, it exerts a partial estrogen agonist activity on the endometrium, bone (helping to preserve postmenopausal bone mineral density) and the lipid profile.
| Routes and Directions | Critical Pharmacokinetics | Main Adverse Effects |
|---|---|---|
| Approved: Adjuvant treatment of estrogen receptor-positive (ER+) breast cancer in pre- and postmenopausal women; ER+ metastatic breast cancer treatment; reduced risk of contralateral breast cancer. | Via: PO (daily tablets). Metabolism: Mainly hepatic. The CYP2D6 isoform is critical for conversion to the most active metabolite endoxifen. t1/2: Original drug: 5-7 days. Endoxifen: 14 days (due to extensive enterohepatic recirculation). | Hot flashes: Very common moderate vasomotor symptoms. Gynecological: Abnormal vaginal discharge, increased risk of hyperplasia and endometrial cancer due to uterine agonist activity. Thromboembolism (severe): Increased risk of deep vein thrombosis (DVT) and pulmonary embolism (EP). Mild hepatotoxicity. |
Pearl of Interaction: CYP2D6 and SSRI (Hot Flash Treatment)
To treat the common and uncomfortable vasomotor hot flashes induced by tamoxifen, SSRI antidepressants are frequently used. However, drugs such as fluoxetine, paroxetine and bupropion are potent inhibitors of CYP2D6 and almost completely block the biotransformation of tamoxifen into active endoxifen, resulting in loss of antineoplastic efficacy and an increase in tumor recurrence. The use of alternative SSRIs that do not significantly inhibit CYP2D6 such as venlafaxine or citalopram is preferred.
Adult Dosage and Contraindications
Standard Dosage: 20 mg PO once daily continuously for a recommended adjuvant period of 5 to 10 years.
Absolute Contraindications: Confirmed history of venous thromboembolism (DVT/PE); concomitant use with coumarins; patients with suspected pre-existing endometrial hyperplasia.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Immunology, Oncology and Toxicology
- Cluster
- Basic Oncology