Tamoxifen
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.
Mechanism of effect
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.
Pharmacodynamic
Tamoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Tamoxifen has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity.
Pharmacokinetics
• Half-Life: 7-14 hr
• Peak Plasma Time: 3-6 hr
• Protein binding: 99%
• Peak Plasma Concentration: 40 ng/mL
• Metabolism: by hepatic P450 enzyme CYP2C9, CYP2D6, CYP3A4
• Metabolites: N-desmethyl tamoxifen, endoxifen
• Excretion: Feces (65%), urine (9%)
Drug indications
metastatic breast cancerDosage
Usual Adult Dose for Breast Cancer
For the treatment of metastatic breast cancer in women and men:
20 to 40 mg orally Dosages greater than 20 mg should be given in divided doses (morning and evening).
For the treatment of women with Ductal Carcinoma in Situ, following breast surgery and radiation:
20 mg orally daily for 5 years.
To reduce the incidence of breast cancer in women at high risk for breast cancer:
20 mg orally daily for 5 years.
Usual Adult Dose for Breast Cancer – Adjuvant
For the treatment of node-positive breast cancer in postmenopausal women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation:
10 mg orally 2 to 3 times a day for 5 years.
Usual Adult Dose for Breast Cancer-Palliative
10 to 20 mg orally twice a day
A beneficial response may not be evident for several months after initiation of therapy.
Usual Pediatric Dose for McCune-Albright Syndrome
For use in girls age 2 to 10 years with McCune-Albright Syndrome and precocious puberty:
20 mg once a day. The duration of treatment is up to 12 months.
Usual Pediatric Dose for Precocious Puberty
For use in girls age 2 to 10 years with McCune-Albright Syndrome and precocious puberty:
20 mg once a day. The duration of treatment is up to 12 months.
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Data not available
Side effects
nausea , Angioedema , flushing , Depression , edema , Cough , Bone pain , anorexia , syncope , Cataracts , decreased libido , corneal changes , ovarian cysts , tirednessInteractions
Carbamazepine , Albendazol , Acetaminophen , Aspirin , Acenocoumarol , Afatinib , Aldosterone , Mirabegron , Ziprasidone , ritonavir , nelfinavir , Dolasetron , Lenalidomide , vandetanib , sparfloxacin , Mefloquine , Dofetilide , Anagrelide , triparanol , Abiraterone , Peginterferon alfa-2b , Halofantrine , Grepafloxacin , Dexfenfluramine , Edoxaban , Lorlatinib , Dacomitinib , Gadofosveset , riociguat , Naltrexone and Bupropion , Bepridil , bedaquiline , Remdesivir , Cannabidiol , anastrozole , Fidaxomicin , fluoroestradiol F 18 , DienestrolAlerts
Black Box Warnings
- For women with ductal carcinoma in situ (DCIS) and women at high risk for breast cancer:
Uterine malignancies, stroke, and pulmonary embolism reported with use in risk-reduction setting (women with ductal carcinoma in situ and women at high risk for breast cancer).
Cautions
- History of thromboembolism (CA treatment); tamoxifen significantly increases risk of venous thromboembolism
- Coumarin anticoagulation (CA treatment)
- CYP2D6 polymorphism-CYP2D6 converts tamoxifen to active metabolite endoxifen; lowered CYP2D6 activity or concomitant CYP2D6 inhibitors may reduce tamoxifen efficacy
- Bone metastases
- Thrombocytopenia
- Cholestasis, fatty liver, hepatic necrosis, and hepatitis reported
- Leukopenia
- Postmarketing cases of hyperlipidemia reported
- Decreased visual acuity, corneal changes, retinal vein thrombosis
- Flushing and increased bone pain and/or tumor pain sometimes associated with good tumor response
- Chronic use for prevention may result in increased risk of stroke, pulmonary embolism, endometrial cancer, uterine sarcoma, cataract
- Avoid pregnancy
Points of recommendation
You should not use tamoxifen if you are allergic to it.
You should not use tamoxifen to reduce your risk of breast cancer if you are also taking a blood thinner such as warfarin (Coumadin, Jantoven).
Do not take tamoxifen if you are pregnant. It could harm the unborn baby. Avoid becoming pregnant while you are using this medicine, and for at least 2 months after your treatment ends.
Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy while taking tamoxifen. Ask your doctor about using non hormonal birth control (condom, diaphragm with spermicide, or intrauterine device/IUD).
If you are taking tamoxifen to reduce your risk of breast cancer , you may need to take your first dose while you are having a menstrual period. You may also need to have a pregnancy test before you start taking tamoxifen, to make sure you are not pregnant. Follow your doctor's instructions.
Taking tamoxifen may increase your risk of uterine cancer, stroke, or a blood clot in the lung, which can be fatal. Talk with your doctor about your specific risks in taking this medicine.
To make sure tamoxifen is safe for you, tell your doctor if you have:
• a history of stroke or blood clot;
• liver disease;
• high cholesterol or triglycerides (a type of fat in the blood);
• a history of cataracts; or
• if you are receiving chemotherapy or radiation.
It is not known whether tamoxifen passes into breast milk or if it could harm a nursing baby. This medicine may slow breast milk production. You should not breast-feed while taking tamoxifen.
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