Letrozole

Indications

Letrozole is used for: Breast cancer

Adult Dose

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.

Child Dose

Renal Dose

Administration

May be taken with or without food.

Contra Indications

Premenopausal women and children; hypersensitivity.

Precautions

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)

Pregnancy-Lactation

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

Interactions

Plasma levels reduced by tamoxifen.

Adverse Effects

Side effects of Letrozole : 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.

Mechanism of Action

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.