Gyraxen Special Precautions

Suppression of menstruation has been observed in a proportion of pre-menopausal patients receiving Tamoxifen for the treatment of breast cancer. Reversible cystic ovarian swelling has occasionally been observed when such women have been treated with Tamoxifen 40 mg twice daily for short periods.
Hypercalcaemia has been reported in a small number of patients with bony metastases when treated with Tamoxifen. In such cases therapy should be stopped and the patient may be treated by rehydration, corticosteroids and if necessary mithramycin. There have been reports of serious potentiation of coumarin-type anticoagulants (Warfarin) by Tamoxifen. Patients taking coumarin-type anticoagulants require close monitoring on the introduction or withdrawal of Tamoxifen.
Menstruation is suppressed in a proportion of pre-menopausal women receiving Tamoxifen 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 properties of Tamoxifen. Any patient receiving or having previously received Tamoxifen who report abnormal gynaecological symptoms, especially vaginal bleeding, or who presents with menstrual irregularities, vaginal discharge and symptoms such as pelvic pain or pressure should be promptly investigated.
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.
In patients with breast cancer, 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.
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 for all patients before treatment with tamoxifen. In patients with breast cancer, this risk is also increased by concomitant chemotherapy. Long-term anti-coagulant prophylaxis may be justified for some patients with breast cancer who have multiple risk factors for VTE.
Surgery and immobility: For patients being treated for infertility, tamoxifen should be stopped at least 6 weeks before surgery or long-term immobility (when possible) and re-started only when the patient is fully mobile. For patients with breast cancer, 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 anti-coagulant treatment.
If any patient presents with VTE, tamoxifen should be stopped immediately and appropriate anti-thrombosis measures initiated. In patients being treated for infertility, tamoxifen should not be re-started unless there is a compelling alternative explanation for their thrombotic event. In patients receiving tamoxifen for breast cancer, the decision to re-start tamoxifen should be made with respect to the overall risk for the patient. In selected patients with breast cancer, 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 an uncontrolled trial in 28 girls aged 2–10 years with McCune Albright Syndrome (MAS), who received 20 mg once a day for up to 12 months duration, mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. While this finding is in line with the pharmacodynamic properties of tamoxifen, a causal relationship has not been established.
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.
Concomitant medications that inhibit (CYPD2D6 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.