Tamoxifen Teva 20 mg

/ Teva

The recommended daily dose of tamoxifen is normally 20 mg. No additional benefit, in terms of delayed recurrence or improved survival in patients, has been demonstrated with higher doses. Substantive evidence supporting the use of treatment with 30-40 mg per day is not available, although these doses have been used in some patients with advanced disease

Palliative treatment of breast cancer, generally in post-menopausal women, either alone or in combination with other modalities.

* Pregnancy. Premenopausal patients must be carefully examined before treatment to exclude the possibility of pregnancy.
* Hypersensitivity to the active substance or to any of the excipients.
* Concurrent anastrozole therapy

Menstrual Suppression
Menstruation is suppressed in a proportion of premenopausal women receiving tamoxifen for the treatment of breast cancer.
Endometrial Changes and Cancer Risk
An increased incidence of endometrial changes including hyperplasia, polyps, cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours), has been reported in association with tamoxifen treatment. The underlying mechanism is unknown but may be related to the oestrogen-like effect of tamoxifen.
There are several factors that influence the risk of developing endometrial cancer, with the majority of risk factors affecting oestrogen levels. Therefore, tamoxifen treatment may increase the incidence of endometrial cancer.
Any patient receiving or having previously received tamoxifen who report abnormal gynaecological symptoms, especially non-menstrual vaginal bleeding, or who presents with menstrual irregularities, vaginal discharge and symptoms such as pelvic pain or pressure should be promptly investigated.
Venous thromboembolism

A 2-3-fold increase in the risk for VTE has been demonstrated in healthy
tamoxifen-treated women.
If suggestive of a prothrombotic risk, patients should be screened for thrombophilic factors. Patients who test positive should be counselled
regarding their thrombotic risk. The decision to use tamoxifen in these patients
should be based on the overall risk to the patient. In selected patients, the use of tamoxifen with prophylactic anticoagulation may be justified.
The risk of VTE is further increased by severe obesity, increasing age and all other risk factors for VTE. The risks and benefits should be carefully considered before treatment with tamoxifen. This risk is also increased by concomitant chemotherapy. Long-term anticoagulant prophylaxis may be justified for some patients who have multiple risk factors for VTE.
Surgery and immobility Tamoxifen treatment should only be stopped if the risk of tamoxifen-induced thrombosis clearly outweighs the risks associated with interrupting treatment. All patients should receive appropriate thrombosis
prophylactic measures and should include graduated compression stockings for the period of hospitalisation, early ambulation, if possible, and anticoagulant treatment.
If any patient presents with VTE, tamoxifen should be stopped immediately and appropriate anti-thrombosis measures initiated. The decision to re-start tamoxifen should be made with respect to the overall risk for the patient. In selected patients, the continued use of tamoxifen with prophylactic anticoagulation may be justified.
In delayed microsurgical breast reconstruction tamoxifen may increase the risk of microvascular flap complications.
QTc Prolongation
Tamoxifen at the recommended dose, may prolong the QTc interval on the electrocardiogram (ECG).
ECG and electrolyte monitoring are recommended in patients with underlying risks of QT prolongation and cardiac comorbidities.
Drug Interactions
Concomitant medications that inhibit CYP2D6 may lead to reduced concentrations of the active metabolite endoxifen. Therefore, potent inhibitors of CYP2D6 (e.g. paroxetine, fluoxetine, quinidine, cinacalcet or bupropion) should whenever possible be avoided during tamoxifen treatment.
Toxic epidermal necrolysis
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life threatening or fatal, have been reported in association with tamoxifen. If signs
and symptoms suggestive of these reactions appear, tamoxifen should be withdrawn immediately and an alternative treatment considered (as appropriate). If the patient has developed a serious reaction such as SJS or TEN with the use of tamoxifen, treatment with tamoxifen must not be restarted in this patient at any time.
Exacerbation of hereditary angioedema
In patients with hereditary angioedema, tamoxifen may induce or exacerbate symptoms of angioedema.

Very common: Fluid retention, Hot flushes, Nausea, Skin Rash, Vaginal bleeding, Vaginal discharge, Fatigue, Depression.
Common: Uterine fibroids, Anaemia, Hypersensitivity reactions, Ischaemic cerebrovascular events, Headache, Light headedness, Sensory disturbances (including paraesthesia and dysgeusia), Cataracts, Retinopathy, Thromboembolic events (including deep vein thrombosis, microvascular thrombosis and pulmonary embolism), Vomiting, Diarrhoea, Constipation, Changes in liver enzymes, Fatty liver, Alopecia, Leg cramp, Myalgia, Pruritus valvae, Endometrial changes (including hyperplasia and polyps), Elevated triglycerides.
See prescribing information for full details.

Coumarin-Type Anticoagulants: When tamoxifen 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.
Cytotoxic Agents: When tamoxifen is used in combination with cytotoxic agents for the treatment of breast cancer, there is increased risk of thromboembolic events occurring. Because of this increase in risk of VTE, thrombosis prophylaxis should be considered for these patients for the period of concomitant chemotherapy.
CYP3A4 Inducers: As tamoxifen is metabolised by cytochrome P450 3A4, care is required when coadministering with drugs, such as rifampicin, known to induce this enzyme as tamoxifen levels may be reduced. The clinical relevance of this reduction is unknown.
CYP2D6 Inhibitors: Pharmacokinetic interaction with CYP2D6 inhibitors, showing a reduction in plasma level of an active tamoxifen metabolite, 4-hydroxy-N- desmethyltamoxifen (endoxifen), has been reported in the literature. Pharmacokinetic interaction with CYP2D6 inhibitors, showing a 65-75% reduction in plasma levels of one of the more active forms of the drug, i.e. endoxifen, has been reported in the literature. Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants (e.g. paroxetine) in some studies. As a reduced effect of tamoxifen cannot be excluded, co-administration with potent CYP2D6 inhibitors (e.g. paroxetine, fluoxetine, quinidine, cinacalcet or bupropion) should whenever possible be avoided.

Women of childbearing potential: Women should be advised not to become pregnant whilst taking tamoxifen and for nine months following the cessation of therapy 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, should they become pregnant whilst taking tamoxifen or within nine months of cessation of therapy.
Pregnancy: Tamoxifen 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 tamoxifen, although no causal relationship has been established.
Lactation: Limited data suggest that tamoxifen and its active metabolites are excreted and accumulate over time in human milk, therefore the drug is not recommended during breast-feeding. The decision either to discontinue nursing or discontinue tamoxifen should take into account the importance of the drug to the mother.