NOLVADEX-D

What it is

NOLVADEX is a film-coated tablet containing tamoxifen citrate. NOLVADEX-D tablets each contain tamoxifen citrate (30.4 mg) equivalent to 20 mg of tamoxifen. NOLVADEX is a non-steroidal, 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.

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

For treatment of breast cancer, the initial dose is 20 mg once daily. In advanced breast cancer, if no response is seen, dosage may be increased to 40 mg once daily. For primary reduction of breast cancer risk, the recommended maximum dose is 20 mg daily for 5 years.

Key safety warnings

An increased incidence of endometrial changes including hyperplasia, polyps, cancer and uterine sarcoma (mostly malignant mixed Mullerian tumours) has been reported in association with NOLVADEX treatment. The incidence and pattern of this increase suggest that the underlying mechanism is related to the oestrogenic properties of NOLVADEX. Any patients receiving or having previously received NOLVADEX, 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 NOLVADEX therapy. When NOLVADEX is coadministered with chemotherapy, there may be a further increase in the incidence of thromboembolic effects. Cases of visual disturbances, including infrequent reports of corneal changes, and common reports of retinopathy have been described in patients receiving NOLVADEX therapy. Cataracts have commonly been reported in association with the administration of NOLVADEX. NOLVADEX should be used with caution in patients with existing leucopenia or thrombocytopenia. Leucopenia has been observed following the administration of NOLVADEX sometimes in association with anaemia and/or thrombocytopenia. Neutropenia has been reported on rare occasions; this can sometimes be severe and rarely cases of agranulocytosis have been reported. NOLVADEX at the recommended dose may prolong the QTc interval on the electrocardiogram (ECG) in patients with underlying risks for QT prolongation and cardiac comorbidities. ECG and electrolyte monitoring are recommended in such patients.

Contraindications

NOLVADEX must not be given during pregnancy. In premenopausal women, the possibility of pregnancy must be excluded before starting tamoxifen. NOLVADEX 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, NOLVADEX 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 is listed on the PBS as a restricted benefit with four items, at an ex-manufacturer price of A$4.40.

Regulatory history

NOLVADEX-D was first registered on the ARTG on 11 July 1991. In March 2016, the PBAC recommended a Restricted Benefit listing of tamoxifen for the reduction of breast cancer risk in patients at moderate to high risk of breast cancer, on the basis of acceptable cost-effectiveness compared to watchful waiting.