GENOX

What it is

Tamoxifen citrate is a nonsteroidal triphenylethylene based drug which displays a complex spectrum of oestrogen antagonist and oestrogen agonist like pharmacological effects in different tissues. In breast cancer patients, at the tumour level, tamoxifen acts primarily as an antioestrogen, preventing oestrogen binding to the oestrogen receptor. GENOX is available as 10 mg and 20 mg tablets of tamoxifen citrate.

Approved indications

— Treatment of breast cancer. — Primary reduction of breast cancer risk in women either at moderately increased risk (lifetime breast cancer risk 1.5 to 3 times the population average) or high risk (lifetime breast cancer risk greater than 3 times the population average).

Dosing overview

GENOX reduces, but does not eliminate, the risk of breast cancer. In clinical trials, GENOX decreased the incidence of oestrogen receptor-positive tumours, but did not alter the incidence of oestrogen receptor-negative tumours.

Key safety warnings

An increased incidence of endometrial changes including hyperplasia, polyps and cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours) has been reported in association with tamoxifen treatment, with the underlying mechanism related to the oestrogenic properties of tamoxifen. Any patients receiving or having previously received GENOX who report abnormal gynaecological symptoms, especially non-menstrual vaginal bleeding, should be promptly investigated. There is evidence of an increased incidence of thromboembolic events, including deep vein thrombosis and pulmonary embolism, during GENOX therapy, and when GENOX is coadministered with chemotherapy, there may be a further increase in the incidence of thromboembolic effects. For treatment of breast cancer, the risks and benefits of GENOX should be carefully considered in women with a history of thromboembolic events. Cases of visual disturbances, including infrequent reports of corneal changes, and common reports of retinopathy have been described in patients receiving tamoxifen therapy, and cataracts have commonly been reported in association with the administration of tamoxifen. GENOX should be used cautiously in patients with existing leucopenia or thrombocytopenia, as leucopenia has been observed following the administration of tamoxifen, sometimes in association with anaemia and/or thrombocytopenia, and neutropenia has been reported on rare occasions and can sometimes be severe and rarely cases of agranulocytosis have been reported. GENOX at the recommended dose may prolong the QTc interval on the electrocardiogram (ECG) in patients with underlying risks for QT prolongation and cardiac comorbidities, and ECG and electrolyte monitoring are recommended in such patients.

Contraindications

GENOX must not be given during pregnancy. GENOX should not be given to patients who have experienced hypersensitivity to the product or any of its ingredients. When considered for primary reduction of breast cancer risk, GENOX is contraindicated in women who require concomitant coumarin-type anticoagulant therapy or in women with a history of deep vein thrombosis or pulmonary embolus.

PBS listing

The 20 mg tablet strength is listed on the PBS with a restricted restriction type and an ex-manufacturer price of A$8.80.

Regulatory history

GENOX was first listed on the Australian Register of Therapeutic Goods on 3 June 1992, with two tablet strengths registered: 10 mg and 20 mg tablets of tamoxifen citrate. The product information document was first approved on 26 September 2001.