Tamoxifen

Indications

Tamoxifen is used for: Breast cancer

Adult Dose

Oral Breast Cancer Treatment 20 mg daily as a single or in 2 divided doses. Max: 40 mg daily. Continue with adjuvant therapy for at least 5 years For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10 Breast Cancer Prevention Indicated to reduce the incidence of breast cancer in women at high risk for breast cancer; high risk is defined as women aged >35 years with a 5-year predicted risk of breast cancer >1.67% (calculated by the Gail Model) Adult: 20 mg daily for 5 yr. Data are limited for use >5 yr in the risk-reduction setting Anovulatory infertility Adult: 20 mg daily on days 2-5 of the menstrual cycle, increase if necessary in subsequent cycles. Max: 80 mg daily. Women w/ irregular menstruation: Initial course may begin on any day and a 2nd course may start 45 days later.

Child Dose

Renal Dose

Administration

May be taken with or without food.

Contra Indications

History of DVT or pulmonary embolism. Pregnancy and lactation. Concomitant coumarin-type anticoagulant therapy.

Precautions

Patient w/ leucopenia and thrombocytopenia, hyperlipidaemias. Monitoring Parameters Perform periodic CBC (e.g. platelet counts) and LFTs. Routine gynaecological monitoring and any abnormal symptoms (e.g. abnormal vag bleeding or discharge, pelvic pain, menstrual irregularities). Lactation: not known if excreted in breast milk, do not nurse

Pregnancy-Lactation

Interactions

Increases dopaminergic effect of bromocriptine. Increased risk of thromboembolic events w/ cytotoxic drugs. Increased risk of bleeding w/ platelet aggregation inhibitors. May mutually reduce effects w/ hormone preparations particularly oestrogens (e.g. OCs). Reduced plasma levels w/ CYP3A4 inducers (e.g rifampicin) and CYP2D6 inhibitors. Increased plasma levels w/ CYP3A4 inhibitors. Potentially Fatal: Significant increase in anticoagulant effect w/ coumarin-type anticoagulants (e.g. warfarin).

Adverse Effects

Side effects of Tamoxifen : >10% Hot flashes (64%),Vaginal discharge (30%),Amenorrhea (16%),Menstrual changes (13%) 1-10% Oligomenorrhea (9%),Cataracts (8%),Bone pain (6%),Nausea (5%),Cough (4%),Edema (4%),Fatigue (4%),Musculoskeletal pain (3%),Ovarian cyst (3%),Depression (2%),Abdominal cramps (1%),Anorexia (1%) <1% Angioedema,Corneal changes,Loss of libido,Endometrial cancer,Pancreatitis,Retinal vein thrombosis,Stroke,Uterine fibroids Potentially Fatal: Blood dyscrasias, cholestasis, hepatitis, hypercalcaemia in patients with bone metastasis, thromboembolic events. Increased risk of endometrial cancer and uterine sarcoma.

Mechanism of Action

Tamoxifen, a triphenylethylene derivative, produces a nuclear complex by competitively binding to oestrogen receptors on tumours and other tissue targets thus, decreasing DNA synthesis and inhibiting oestrogen effect. It is only cytostatic rather than cytotoxic due to accumulation of cell in G0 and G1 phases.