Letrozole

Breast cancer

Oral Advanced or locally advanced breast cancer ; Adjuvant therapy for postmenopausal women with hormone receptor positive early breast cancer Adult: 2.5 mg once daily. Hepatic impairment: Reduce dose by 50% in patients with cirrhosis and severe hepatic impairment; recommended dose: 2.5 mg on alternate days.

May be taken with or without food.

Premenopausal women and children; hypersensitivity.

Severe renal impairment; severe hepatic impairment; osteoporosis. Caution when driving or operating machinery. Lactation: not known if excreted in breast milk (for post-menopausal women)

Not Classi Pregnancy Based on post-marketing reports, findings from animal studies and mechanism of action, therapy can cause fetal harm and is contraindicated for use in pregnant women; in post-marketing reports, use during pregnancy resulted in cases of spontaneous abortions and congenital birth defects; however, data are insufficient to inform a drug-associated risk Contraception Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after last dose Infertility Therapy may impair fertility in females and males of reproductive potential Lactation Not known if therapy is present in human milk; there are no data on effects on breastfed infant or milk production; exposure of lactating rats to drug was associated with impaired reproductive performance of male offspring; because of potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while receiving therapy and for at least 3 weeks after last dose

Plasma levels reduced by tamoxifen.

Hot flushes, arthralgia, nausea, vomiting, fatigue, dizziness, headache, dyspepsia, constipation, diarrhoea, anorexia, alopoecia, increased sweating, rash, peripheral oedema, osteoporosis, musculoskeletal pain, vaginal irritation. Potentially Fatal: Thromboembolic events.

Letrozole competitively binds to the heme group of aromatase, a cytochrome P450 enzyme which catalyzes conversion of androgen to oestrogen, leading to inhibition of the enzyme and a significant reduction in plasma oestrogen levels.