Tamoxifen is an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth.
Mechanism of Action of Tamoxifen
Tamoxifen is a nonsteroidal agent that binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or a 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.
Or
Tamoxifen is a nonsteroidal agent with potent antiestrogenic properties. The antiestrogen effects may be related to tamoxifen’s ability to compete with estrogen for binding sites in target tissues such as the breast. Tamoxifen competes with estradiol for estrogen receptor protein in cytosols derived from human breast adenocarcinomas. Tamoxifen has been shown to inhibit the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. Tamoxifen appears to exert its antitumor effects by binding the estrogen receptors in this rat model.
Indications of Tamoxifen
- Tamoxifen is indicated for the treatment of metastatic breast cancer in women and men and ductal carcinoma in Situ.
- Breast Cancer, Male
- Breast Cancer, Adjuvant
- Breast Cancer
- Breast Cancer, Metastatic
- Breast Cancer, Palliative
- Breast Cancer, Prevention
- McCune-Albright Syndrome
- Precocious Puberty
- Cancer of the Ovary
- Desmoid Tumors
- Endometrial Cancers
- Gynecomastia
- Invasive Breast Carcinoma
- Metastatic Breast Cancer
- Puberty, Precocious
Therapeutic Uses of Tamoxifen
- Anticarcinogenic Agents; Antineoplastic Agents, Hormonal; Carcinogens; Estrogen Antagonists
- Antiestrogen; antineoplastic (hormonal).
- Tamoxifen is indicated for adjuvant treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. Data are insufficient to predict which women are most likely to benefit and to determine if tamoxifen provides any benefit in women with tumors of less than 1 cm.
- Tamoxifen is also indicated for adjuvant treatment of axillary node-positive breast cancer in postmenopausal women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes.
- Tamoxifen is indicated to reduce the risk of developing breast cancer in women who have been determined to be at high risk for developing this cancer. A woman is considered to be at high risk if she is at least 35 years of age and has a 5-year predicted the risk of developing breast cancer greater than or equal to 1.67%.
- Tamoxifen is indicated to reduce the risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) who have undergone breast surgery and radiation treatment.
- Tamoxifen is indicated, in combination with other agents, in the treatment of malignant melanoma.
- Tamoxifen, in combination with other agents, is considered reasonable medical therapy at some point in the management of endometrial carcinoma.
Contra-Indications of Tamoxifen
- The high amount of calcium in the blood
- Decreased blood platelets
- decreased white blood cells
- Lung embolism
- Stroke
- Obstruction of a blood vessel by a blood clot
- A blood clot in a deep vein of the extremities
- Liver problems
- Pregnancy
- A mother who is producing milk and breastfeeding
- Allergies to Tamoxifen Analogues
Dosage of Tamoxifen
Strengths: 10 mg; 20 mg; 10 mg/5 mL
Breast Cancer
Metastatic breast cancer in women and men
- 20 to 40 mg orally daily for 5 years; doses greater than 20 mg should be given in divided doses (morning and evening)
DCIS 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
Side Effects of Tamoxifen
The Most Common
- Absent, missed, or irregular periods
- the decrease in the amount of urine
- feeling of warmth
- menstrual changes
- noisy, rattling breathing
- redness of the face, neck, arms and occasionally, upper chest
- skin changes
- stopping of menstrual bleeding
- swelling of the fingers, hands, feet, or lower legs
- troubled breathing at rest
- weight gain or loss
- white or brownish vaginal discharge
Common
- Anxiety
- blistering, peeling, or loosening of the skin and mucous membranes
- blurred vision
- cataracts in the eyes or other eye problems
- change in vaginal discharge
- chest pain
- confusion
- a cough
- dizziness
- fast heartbeat
- fever
- hoarseness
- lightheadedness
- lower back or side pain
- pain or feeling of pressure in the pelvis
More common
- Black, tarry stools
- clay colored stools
- a cough or hoarseness
- dark urine
- decreased appetite
- fever or chills
- a headache
- loss of appetite
- lower back or side pain
- nausea, vomiting
- painful or difficult urination
- pinpoint red spots on the skin
Drug Interactions of Tamoxifen
Tamoxifen may interact with following drugs, supplements & may change the efficacy of drugs
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- apixaban
- aprepitant
- “azole” antifungal medications (e.g., fluconazole, ketoconazole, voriconazole)
- barbiturates (e.g., phenobarbital, secobarbital)
- bicalutamide
- bosentan
- bosutinib
- bupropion
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- capecitabine
- carbamazepine
- cetirizine
- chloramphenicol
- clobazam
- cyclosporine
- diphenhydramine
- disopyramide
- domperidone
- estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
- fusidic acid
- gemfibrozil
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- other cancer medications (e.g., doxorubicin, methotrexate, paclitaxel)
- pazopanib
- peginterferon Alfa-2b
- pentamidine
- phenytoin
- pioglitazone
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- ranitidine
- repaglinide
- rosiglitazone
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- sotalol
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- “sulfa” antibiotics (e.g., sulfadiazine, sulfamethoxazole, sulfisoxazole)
- tricyclic antidepressants (e.g., clomipramine, desipramine, trimipramine)
- trimethoprim
- vandetanib
- vemurafenib
- warfarin
- zafirlukast
Pregnancy & Lactation
FDA Pregnancy Category – D
Pregnancy
This medication may cause birth defects or death to the developing fetus and should not be used during pregnancy. Effective birth control should be used while taking this medication and for about 2 months after finishing it. Tell the doctor immediately if you become pregnant while taking this medication.
Lactation
It is not known if tamoxifen passes into breast milk. If you breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.
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