Letrozole (Brand Name: Femara) is an orally active nonsteroidal compound that reversibly inhibits aromatization all over the body, as well as that within the breast cancer cells, resulting in nearly total estrogen deprivation.It is a selective inhibitor of estrogen formation.it inhibits the estrogen synthesis by inhibition of aromatase enzyme that is crucial for the formation of estrogen.The proliferation of estrogen-dependent breast cancer is suppressed to a greater extent than with tamoxifen.
Letrozole (Femara) is quickly absorbed with 100% bioavailability, Slow metabolism, the large volume of Distribution, and Time half (t½) of approximately 40 hours.
Femara Mechanism Of Action
Letrozole is a Selective nonsteroidal inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens.In adult nontumor- and tumor-bearing female animals, letrozole is as effective as ovariectomy in reducing uterine weight, elevating blood serum luteinizing hormone, and inflicting the regression of estrogen-dependent tumors. In distinction to ovariectomy, treatment with letrozole doesn’t cause a rise in serum follicle-stimulating hormone. Letrozole selectively inhibits gonadal steroidogenesis, however, has no important effect on adrenal mineralocorticoid or glucocorticoid synthesis.Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, leading to a reduction of estrogen synthesis in all tissues. Treatment of women with letrozole significantly lowers blood serum estrone, estradiol and estrone sulfate and has not been shown to significantly have an effect on adrenal corticosteroid synthesis, aldosterone synthesis, or synthesis of thyroid hormones.
- It is used in estrogen receptor-positive early breast cancer in postmenopausal women,
- Used in Early invasive breast cancer in postmenopausal ladies when five years of tamoxifen therapy have failed to work.
- Advanced breast cancer in postmenopausal women.
- It is additionally employed in pre-operative treatment in postmenopausal women with localized hormone receptor-positive breast cancer.
- Fertility physicians have used it since 2001 unauthorized because it has fewer side effects such as Clomid (Clomiphene) and a lower risk of multiple pregnancies.
It is contraindicated in the following conditions:
- Premenopausal women,
- Liver disease (especially cirrhosis), Contraindicated in individuals best-known hypersensitivity to the active substance, or to any of the excipients.
- Osteopenia (low bone mineral density),
- High cholesterol; or
- if you also take tamoxifen.
- The use of Femara might cause decreases in the density of your bones, will increase in bone fractures and osteoporosis.
Use of Femara with tamoxifen resulted in an exceedingly reduction of letrozole plasma levels of 38th on the average Clinical expertise in different breast cancer trials indicates that the therapeutic result of
Femara therapy isn’t impaired if Femara is run immediately after tamoxifen.
while an interaction study with warfarin showed no clinically important effect of letrozole on warfarin pharmacokinetics.
Apart from this, A pharmacokinetic interaction study with cimetidine showed no clinically important effect on letrozole pharmacokinetics.
Femara Side effects:
- Most common side effects associated with the use of femara (letrozole) includes; Nausea, Vomiting, Hot flushes, dyspepsia, dizziness, headache, diarrhea, constipation, anorexia, depression, hypercholesteremia, raised sweating, alopecia, increased craving, peripheral oedema, skin rashes, bone fracture, osteoporosis etc
- Less common side effects include tachycardia, high blood pressure, palpitation, cough, dyspnea, anxiety, insomnia, memory impairment, taste distrurbance, urticaria, pruritis, dry skin, urinary frequency, abdominal pain, thrombophelbitis, urinary tract infection, viginal discharge, vigina bleeding, pyrexia, breast pain, cataract, blurred vision, eye irritation, leucopenia, carpal tunnel syndrome, arthritis, tumor pain, and general oedema.
- Very rare side effect includes: arterial thrombosis, cerebrovascular infarction, and embolism.
Femara in Pregnancy & Breast Feeding:
Femara should be avoided in pregnant women because it causes birth defects in a child.Manufacturer recommendation the utilization of contraceptives until postmenopausal status totally established.
While just in case of lactating women it’s unknown if letrozole is present in human milk. There isn’t any information on the effects of letrozole on the breastfed infant or milk production
The standard recommended dose of Letrozole for all type of breast cancer treatment is 2.5 mg per day without regard to meals.