Tamoxigen
Tamoxigen Uses, Dosage, Side Effects, Food Interaction and all others data.
Tamoxigen 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.
Tamoxigen is a selective estrogen receptor modulator that inhibits growth and promotes apoptosis in estrogen receptor positive tumors. It has a long duration of action as the active metabolite N-desmethyltamoxifen has a half life of approximately 2 weeks. It has a narrow therapeutic index as higher doses can lead to breathing difficulty or convulsions. Tamoxigen administration is also associated with an increased incidence of uterine malignancies.
| Trade Name | Tamoxigen |
| Availability | Prescription only |
| Generic | Tamoxifen |
| Tamoxifen Other Names | Tamoxifen, Tamoxifène, Tamoxifene, Tamoxifeno, Tamoxifenum, trans-Tamoxifen |
| Related Drugs | Supprelin LA, estradiol, anastrozole, letrozole, Premarin, testosterone, Lupron, Arimidex, megestrol, fluorouracil |
| Type | Tablet |
| Formula | C26H29NO |
| Weight | Average: 371.5146 Monoisotopic: 371.224914555 |
| Protein binding | The protein binding of tamoxifen in plasma is over 98% and mostly to serum albumin. |
| Groups | Approved |
| Therapeutic Class | Hormonal Chemotherapy |
| Manufacturer | |
| Available Country | Philippines |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Tamoxigen is used for the treatment of breast cancer.
Tamoxigen is a praparation of Tamoxigen which is a non-steroidal, triphenylene based drug and displays a complex spectrum of oestrogen antagonist and oestrogen agonist like pharmacological effects in different tissues. In breast cancer patients, at the tumour level, Tamoxigen acts primarily as an antioestrogen, preventing oestrogen binding to the oestrogen receptor. Additionally Tamoxigen has been reported to lead to maintenance of bone mineral density in post-menopausal women.
Tamoxigen is also used to associated treatment for these conditions: Breast Cancer, Desmoid Tumors, Endometrial Cancer, Gynecomastia, Invasive Breast Cancer, Invasive Breast Carcinoma, Metastatic Breast Cancer, Ovarian Cancer, Puberty, Precocious, Ovulation induction therapy
How Tamoxigen works
Tamoxigen competitively inhibits estrogen binding to its receptor, which is critical for it's activity in breast cancer cells. Tamoxigen leads to a decrease in tumor growth factor α and insulin-like growth factor 1, and an increase in sex hormone binding globulin. The increase in sex hormon binding globulin limits the amount of freely available estradiol. These changes reduce levels of factors that stimulate tumor growth.
Tamoxigen has also been shown to induce apoptosis in estrogen receptor positive cells. This action is thought to be the result of inhibition of protein kinase C, which prevents DNA synthesis. Alternate theories for the apoptotic effect of tamoxifen comes from the approximately 3 fold increase in intracellular and mitochondrial calcium ion levels after administration or the induction of tumor growth factor β.
Dosage
Tamoxigen dosage
Adults (including elderly): The dosage range is 20 to 40 mg daily, given either in divided doses twice daily or as a single dose once daily.
Side Effects
Side effects can be classified as either due to the pharmacological action of the drug, e.g., hot flushes, vaginal bleeding, vaginal discharge, pruritus vulvae and tumour flare or as more general side effects, e.g., gastrointestinal intolerance, headache, light-headedness and occasionally fluid retention and alopecia. When such side effects are severe, it may be possible to control them by a simple reduction of dosage (within the recommended dose range) without loss of control of the disease.
Skin rashes including isolated reports of erythema multiforme, Stevens Johnson syndrome and bullous pemphigoid and rare hypersensitivity reactions, including angio-oedema have been reported. A small number of patients with bony metastases have developed hypercalcaemia on initiation of therapy.
Falls in platelet count, usually only to 80,000-90,000 per/mm3 but occasionally lower, have been reported in patients taking Tamoxigen for breast cancer.
A number of cases of visual disturbances including infrequent reports of corneal changes and retinopathy have been described in patients receiving Tamoxigen therapy. An increased incidence of cataracts has been reported in association with the administration of the drug. Uterine fibroids and endometrial changes including hyperplasia and polyps have been reported. Cystic ovarian swellings have occasionally been observed in premenopausal women receiving Tamoxigen.
Leucopenia has been observed following the administration of Tamoxigen, sometimes in association with anaemia and/or thrombocytopenia. Neutropenia has been reported on rare occasions; this can sometimes be severe. There is evidence of an increased incidence of thromboembolic events including deep vein thrombosis and pulmonary embolism during Tamoxigen therapy.
Tamoxigen has been associated with changes in liver enzyme levels and on rare occasions with a spectrum of more severe liver abnormalities, including fatty liver, cholestasis and hepatitis. Rarely, elevation of serum triglyceride levels, in some cases with pancreatitis, may be associated with the use of Tamoxigen.
Toxicity
High doses of tamoxifen in animals lead to respiratory difficulty and convulsions. High doses in advanced metastatic cancer patients resulted in acute neurotoxicity seen by tremor, hyperreflexia, unsteady gait, and dizziness. Patients experiencing and overdose should be given supportive treatment as no specific treatment for overdose is suggested.
Precaution
Menstruation is suppressed in a proportion of premenopausal women receiving Tamoxigen for the treatment of breast cancer. An increased incidence of endometrial cancer has seen reported in association with Tamoxigen treatment. The underlying mechanism is unknown, but may be related to the oestrogen-like effect of Tamoxigen. Any patients receiving or having previously received Tamoxigen, who report abnormal gynaecological symptoms, especially vaginal bleeding, should be promptly investigated.
A number of second primary tumors, occurring at sites other than the endometrium and the opposite breast, have been reported in clinical trials, following the treatment of breast cancer patients with Tamoxigen. No causal link has been established and the clinical significance of these observations remains unclear.
Interaction
When Tamoxigen is used in combination with coumarin type anticoagulants, a significant increase in anticoagulant effect may occur. Where such co administration is initiated, careful monitoring of the patient is recommended. When Tamoxigen is used in combination with cytotoxic agents, there is an increased risk of thromboembolic events.
Food Interaction
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of tamoxifen.
- Take with a full glass of water.
- Take with or without food.
[Moderate] GENERALLY AVOID: Due to their estrogenic effect, isoflavones present in soy such as genistein and daidzein may stimulate breast tumor growth and antagonize the antiproliferative action of tamoxifen.
Supportive data are derived primarily from in vitro and animal studies.
In vitro, low concentrations of these phytoestrogens have been found to promote DNA synthesis and reverse the inhibitory effect of tamoxifen on estrogen-dependent breast cancer cell proliferation.
In contrast, high concentrations of genistein greater than 10 microM It is not known if these high concentrations are normally achieved in humans. Plasma concentrations below 4 microM These concentrations are comparable to the low plasma concentrations associated with tumor stimulation reported in animals. In a study of 155 female breast cancer survivors with substantially bothersome hot flashes, a product containing 50 mg of soy isoflavones (40% to 45% genistein; 40% to 45% daidzein; 10% to 20% glycitein) taken three times a day was found to be no more effective than placebo in reducing hot flashes. No toxicity or recurrence of breast cancer was reported during the 9-week study period. In a study consisting of 14 patients who have been receiving tamoxifen treatment at a stable dose of 20 mg (n=13) or 40 mg (n=1) once daily for at least 3 months, coadministration with green tea supplements twice daily for 14 days resulted in no significant differences in the pharmacokinetics of either tamoxifen or endoxifen with respect to peak plasma concentration (Cmax), systemic exposure (AUC), and trough plasma concentration (Cmin) compared to administration of tamoxifen alone. The combination was well tolerated, with all reported adverse events categorized as mild (grade 1) and none categorized as serious or severe (grade 3 or higher) during the entire study. Although some adverse events such as headache, polyuria, gastrointestinal side effects (e.g., constipation, dyspepsia), and minor liver biochemical disturbances were reported more often during concomitant treatment with green tea, most can be attributed to the high dose of green tea used or to the caffeine in green tea. The green tea supplements used were 1000 mg in strength and contained 150 mg of epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea. According to the investigators, the total daily dose of EGCG taken by study participants is equivalent to the amount contained in approximately 5 to 6 cups of regular green tea. However, it is not known to what extent the data from this study may be applicable to other preparations of green tea such as infusions, since the bioavailability of EGCG and other catechins may vary between preparations. Consumption of green tea and green tea extracts during tamoxifen therapy appears to be safe.
Green tea does not appear to have significant effects on the pharmacokinetics of tamoxifen or its primary active metabolite, endoxifen.
MANAGEMENT: Until more information is available, patients treated with tamoxifen may consider avoiding or limiting the consumption of soy-containing products.
Tamoxigen Drug Interaction
Major: diphenhydramine, duloxetine, escitalopramModerate: venlafaxine, venlafaxineUnknown: aspirin, calcium / vitamin d, loratadine, ubiquinone, omega-3 polyunsaturated fatty acids, pregabalin, metoprolol, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, alprazolam, cetirizine
Tamoxigen Disease Interaction
Major: DVT/pulmonary embolismModerate: endometrial dysplasia, hepatic dysfunction, myelosuppression, visual disturbances
Volume of Distribution
The volume of distribution of tamoxifen is approximately 50-60L/kg.
Elimination Route
An oral dose of 20mg reaches a Cmax of 40ng/mL with a Tmax of 5 hours. The metabolite N-desmethyltamoxifen reaches a Cmax of 15ng/mL. 10mg of tamoxifen orally twice daily for 3 months results in a Css of 120ng/mL and a Css of 336ng/mL.
Half Life
The terminal elimination half-life of tamoxifen is 5 to 7 days, while the half-life of N-desmethyltamoxifen, the primary circulating metabolite, is approximately 14 days.
Clearance
The clearance of tamoxifen was 189mL/min in a study of six postmenopausal women.
Elimination Route
Tamoxigen is mainly eliminated in the feces. Animal studies have shown 75% of radiolabelled tamoxifen recovered in the feces, with negligible collection from urine. However, 1 human study showed 26.7% recovery in the urine and 24.7% in the feces.
Pregnancy & Breastfeeding use
Pregnancy: Tamoxigen must not be administered during pregnancy. There have been a small number of reports of spontaneous abortions, birth defects and foetal deaths after women have taken Tamoxigen, although no causal relationship has been established. Reproductive toxicology studies in rats, rabbits and monkeys have shown no teratogenic potential.
Women should be advised not to become pregnant whilst taking Tamoxigen and should use barrier or other nonhormonal contraceptive methods if sexually active. Premenopausal patients must be carefully examined before treatment to exclude pregnancy. Women should be informed of the potential risks to the foetus, if they want to become pregnant whilst taking Tamoxigen or within two months of cessation of therapy.
Lactation: It is not known if Tamoxigen is excreted in human milk and therefore the drug is not recommended during lactation. The decision to discontinue Tamoxigen should take into account in case of the importance of the drug to the lactating mother.
Contraindication
Tamoxigen must not be administered during pregnancy. Tamoxigen should not be given to patients who have experienced hypersensitivity to the product or any of its ingredients.
Storage Condition
Store between 20-25° C. Protect from light.
Innovators Monograph
You find simplified version here Tamoxigen
Tamoxigen contains Tamoxifen see full prescribing information from innovator Tamoxigen Monograph, Tamoxigen MSDS, Tamoxigen FDA label
FAQ
What is Tamoxigen used for?
Tamoxigen used to treat hormone receptor-positive breast cancer. It can greatly reduce the risk of cancer recurrence and invasive cancer.
How does Tamoxigen do to the body?
Tamoxigen attaches to the hormone receptors in the cancer cell, blocking estrogen from attaching to the receptors. This slows or stops the growth of the tumor by preventing the cancer cells from getting the hormones they need to grow.
What cancer does Tamoxigen treat?
Tamoxigen can be used to treat women with breast cancer who have or have not gone through menopause. It can be used in several ways: In women at high risk of breast cancer,Tamoxigen can be used to help lower the risk of developing breast cancer.
What are the side effects of Tamoxigen?
Common side effects of Tamoxigen include:
- Menopause-like symptoms, including hot flashes, night sweats and vaginal dryness.
- Weight gain (more common) or fluid retention (edema).
- Irregular or loss of menstrual periods.
- Leg swelling.
- Nausea.
- Vaginal discharge.
- Skin rash.
- Erectile dysfunction .
- Fatigue.
- Headaches.
How long should I take Tamoxigen?
Most people take Tamoxigen or other hormone therapy for at least five years and sometimes up to 10 years. Treatment length depends on the features of your cancer diagnosis.
How do take I Tamoxigen?
You must take Tamoxigen daily by mouth, preferably at the same time each day.
Is it safe to take Tamoxigen during pregnancy?
Tamoxigen may cause birth defects. You shouldn’t take the medication if you’re pregnant or planning to become pregnant. To prevent pregnancy, talk to your healthcare provider about nonhormonal birth control options.
Is Tamoxigen safe during breasfeeding?
Tamoxigen and its active metabolites are detectable in milk and accumulate in milk over time. It can also suppress lactation. If a mother requires treatment with Tamoxigen, breastfeeding should be avoided.
Can I drink alcohol while taking Tamoxigen?
Alcohol can raise the risk of side effects with Tamoxigen, some of which can be serious. Alcohol makes it harder for Tamoxigen to work properly and should be limited or avoided while you're taking this medication. Alcohol can raise your risk of developing breast cancer.
How does Tamoxigen make me feel?
Some people go through mood swings or feel low or depressed while they are taking Tamoxigen. Or it may be harder to think clearly or concentrate.
Is Tamoxigen really necessary?
Tamoxigen is a highly effective breast cancer treatment. It may significantly lower your risk of breast cancer recurrence or invasive breast cancer. People who are at high risk for breast cancer may take Tamoxigen to reduce their chances of getting the disease.
Does Tamoxigen lower my immune system?
Taking hormone therapy does not affect your immune system.
Does Tamoxigen cause I to gain weight?
Tamoxigen has been loosely associated with weight gain. Studies have tracked weight gain and other side effects of the drug for years. Some resources even list weight gain as a possible side effect.
Can Tamoxigen raise blood pressure?
There was no effect of Tamoxigen on clinic BP.
Does Tamoxigen cause hair loss?
No one goes bald from Tamoxigen but some people do experience thinning hair. Like hair thinning, a lowered libido is common postmenopause and in the setting of reduce estrogen.
Is Tamoxigen an anti inflammatory?
Results suggest that the mechanism of action of Tamoxigen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses.
Is Tamoxigen an anti inflammatory?
Results suggest that the mechanism of action of Tamoxigen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses.
Does Tamoxigen make me tired?
When you start to take Tamoxigen, you may feel tired, drowsy, or feel like you have no energy.
Can Tamoxigen cause memory loss?
memory loss and concentration issues brought on by use of Tamoxigen or aromatase inhibitors.
Does Tamoxigen affect mood?
Tamoxigen does not affect mood or sexual functioning.
Can Tamoxigen cause anxiety?
Clinical evidence suggests the drug increases rates of anxiety and the incidence of hot flashes, both of which may result from reduced action of estrogen.
Can Tamoxigen cause hip pain?
The terrible groin and hip pain is pretty clearly a side effect of the Tamoxigen.
Is Tamoxigen good for my bones?
Taking Tamoxigen slows down bone loss and can reduce the risk of osteoporosis.
Does Tamoxigen make me itchy?
Dry, itchy skin is a common side effect of Tamoxigen.
Is it better to take Tamoxigen at night or morning?
Tamoxigen may be taken at any time of the day but should be taken at the same time each day. it is within 12 hours of the missed dose.
