Nolvadex

Question 1

What are the therapeutic indications of Nolvadex?

Answer 1

‘Tamoxifen’ is indicated for:
1. The treatment of breast cancer.
2. The treatment of anovulatory infertility.
3. The primary prevention of breast cancer in women at moderate or high risk (see section 5.1)

Women aged less than 30 years old were excluded from primary prevention trials so the efficacy and safety of tamoxifen treatment in these younger women is unknown.

Question 2

What are the contraindications of Nolvadex?

Answer 2

General contraindications (all indications)
Tamoxifen should not be used in the following:
* Pregnancy. Pre-menopausal patients must be carefully examined before treatment for all indications to exclude the possibility of pregnancy.
* Hypersensitivity to the active substance or to any of the excipients.
* Concurrent anastrozole therapy.
Treatment for infertility

Tamoxifen should not be used in:
* Patients with a personal or family history of confirmed idiopathic venous thromboembolic events or a known genetic defect.
Primary prevention of breast cancer
Tamoxifen should not be used in:
* Women with a history of deep vein thrombosis or pulmonary embolus.
* Women who require concomitant coumarin-type anticoagulant therapy.

Question 3

What are the Pharmacodynamic properties of Nolvadex

Answer 3

Tamoxifen 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. In the clinical situation, it is recognised that tamoxifen leads to reductions in levels of blood total cholesterol and low density lipoproteins in postmenopausal women of the order of 10 - 20%. Tamoxifen does not adversely affect bone mineral density.

Question 4

What are the Pharmacodynamic properties of Nolvadex

Answer 4

After oral administration, tamoxifen is absorbed rapidly with maximum serum concentrations attained within 4–7 hours. Steady state concentrations (about 300ng/ml) are achieved after four weeks treatment with 40mg daily. The drug is highly protein bound to serum albumin (>99%). Metabolism is by hydroxylation, demethylation and conjugation, giving rise to several metabolites which have a similar pharmacological profile to the parent compound and thus contribute to the therapeutic effect. Excretion occurs primarily via the faeces and an elimination half-life of approximately seven days has been calculated for the drug itself, whereas that for N-desmethyltamoxifen, the principal circulating metabolite, is 14 days.