Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use
Menstruation is suppressed in a proportion of premenopausal women receiving Tamoxifen Teva for the treatment of breast cancer.
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 Teva treatment may increase the incidence of endometrial cancer. In addition, other risk factors include obesity, nulliparity, diabetes mellitus, polycystic ovary syndrome and oestrogen-only HRT. There is also the general risk for endometrial cancer with increasing age.

Any patient receiving or having previously received Tamoxifen Teva 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.

In patients with hereditary angioedema, Tamoxifen Teva may induce or exacerbate symptoms of angioedema.

A number of second primary tumours, 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 tamoxifen. No causal link has been established and the clinical significance of these observations remains unclear.

Venous thromboembolism
•   A 2-3-fold increase in the risk for VTE has been demonstrated in healthy tamoxifen-treated women (see section 4.8).

•       Prescribers should obtain careful histories with respect to the patient’s personal and family history of VTE. 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 (cross-reference section 4.5).

•       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 (see section 4.5). 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.

•    All patients should be advised to contact their doctors immediately if they become aware of any symptoms of VTE.
In delayed microsurgical breast reconstruction Tamoxifen Teva may increase the risk of microvascular flap complications.

In the literature it has been shown that CYP2D6 poor metabolisers have a lowered plasma level of endoxifen, one of the most important active metabolites of tamoxifen (see section 5.2).
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 (see sections 4.5 and 5.2).
Radiation recall has been reported very rarely in patients on tamoxifen who have received prior radiotherapy. The reaction is usually reversible upon temporary cessation of therapy and re-challenge may result in a milder reaction. Treatment with tamoxifen was continued in most cases.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.


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. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. 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.

Effects on Driving

4.7    Effects on ability to drive and use machines
Tamoxifen Teva is unlikely to impair the ability of patients to drive or operate machinery.
However, fatigue has been reported with the use of tamoxifen and caution should be observed when driving or using machinery while such symptoms persist.