Tamoxifen

Tamoxifen is used for: Breast cancer

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.

May be taken with or without food.

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

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 Fetal harm may occur when administered to a pregnant woman FDA re-evaluated genotoxicity data, postmarketing reports, and published literature and found that tamoxifen was genotoxic in nonhuman studies, and results were inconclusive in human studies; available data from postmarketing reports and published literature from women who became pregnant 2-9 months after their last dose of tamoxifen have not identified a drug-associated risk of major birth defects or adverse maternal or fetal outcomes Animal studies In rat and rabbit studies, doses of tamoxifen less than or equal to human doses resulted in increased embryotoxicity, abortions, and altered learning behaviors in the offspring; rodent models showed reproductive tract changes often associated with diethylstilbestrol (DES) in offspring of both sexes Based on animal studies, tamoxifen may impair embryo implantation in females of reproductive potential, however, may not reliably cause infertility; advise women that tamoxifen does not always cause infertility, even in the presence of menstrual irregularity Contraception Confirm pregnancy test in females of reproductive potential before initiation Females: Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for 2 months following the last dose Infertility Based on animal studies, tamoxifen may impair embryo implantation in females of reproductive potential, however, may not reliably cause infertility Advise women that tamoxifen does not always cause infertility, even in the presence of menstrual irregularity Lactation Tamoxifen reported to inhibit lactation Two placebo-controlled studies in over 150 women have shown that tamoxifen significantly inhibits early postpartum milk production; both studies tamoxifen was administered within 24 hr of delivery for between 5 and 18 days; effect of tamoxifen on established milk production is not known There are no data that address whether tamoxifen is excreted into human milk; direct neonatal exposure of tamoxifen to mice and rats (not via breast milk) produced 1) reproductive tract lesions in female rodents (similar to those seen in humans after intrauterine exposure to diethylstilbestrol) and 2) functional defects of the reproductive tract in male rodents such as testicular atrophy and arrest of spermatogenesis Unknown if tamoxifen is excreted in human milk Because of potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed

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).

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.

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.