Letrozole

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Letrozole (Femara) belongs to a group of medicines called aromatase inhibitors. It is a hormonal breast cancer treatment. Growth of breast cancer is frequently stimulated by estrogens. Letrozole reduces the amount of estrogen by blocking an enzyme (“aromatase”) involved in the production of estrogens. As a consequence tumour cells slow or stop growing.

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Contents

[edit] BRAND NAMES

Other brand names: Femar

[edit] STRUCTURE

Letrozole.jpg

[edit] MECHANISM OF ACTION

Many breast cancers have estrogen receptors and growth of these tumors can be stimulated by estrogens. The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women, the principal source of circulating estrogen (primarily estradiol) is conversion of adrenally-generated androstenedione to estrone by aromatase in peripheral tissues, such as adipose tissue, with further conversion of estrone to estradiol.

Letrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations.

[edit] INDICATIONS

FDA-approved use:

  • Early breast cancer:
    • Adjuvant treatment (After surgery) of postmenopausal women with hormone receptor-positive early breast cancer (cancer that has not spread), to reduce the chance of the cancer coming back.
    • Extended adjuvant treatment (After surgery) of postmenopausal women with hormone receptor-positive early breast cancer (cancer that has not spread) who have received 5 years of adjuvant tamoxifen therapy, to reduce the chance of the cancer coming back. (FDA approved)


  • Advanced breast cancer:
    • First line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
    • Second line treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.


Off-label uses:

  • Ovulation induction: Letrozole is used for ovarian stimulation by fertility doctors because it has fewer side-effects than clomiphene (Clomid) and less chance of multiple gestation. Antiestrogenic effects of clomiphene such as poor cervical mucus and thin endometrium are not expected with Letrozole. In addition, because estrogen receptors in the brain are not depleted with Letrozole, normal negative feedback occurs with this drug and generally results in monoovulation.[1] . Letrozole is efficacious in treating women with chronic anovulation, unexplained infertility and diminished ovarian reserve.
  • Letrozole has been also used to treat endometriosis. letrozole resulted in a significant reduction in pelvic pain and stage of endometriosis.[2]

[edit] DOSAGE

Recommended dose in early and advanced breast cancer is 2,5 mg (One tablet) once daily without regard to meals.

In the adjuvant and extended adjuvant setting, treatment with Letrozole should continue for 5 years or until tumour relapse occurs, whichever is first

For patients with advanced breast cancer, treatment with Letrozole should continue until tumor progression is evident.


Ovulation induction (Off-label): Letrozole is typically administered for 5 days, on days 3–7 of the menstrual cycle at doses of 2.5–7.5 mg/day

[edit] CONTRAINDICATIONS

  • Premenopausal women
  • Pregnancy and breastfeeding.
  • Patients with known hypersensitivity to Letrozole

[edit] WARNINGS AND PRECAUTIONS

  • Decrease in bone mineral density: Letrozole lowers circulating estrogen levels, so it may cause a reduction in bone mineral density with a possible consequent increased risk of fracture. Women with a history of osteoporosis and/or fractures, or who are at increased risk of osteoporosis, should have their bone mineral density formally assessed prior to the commencement of therapy and should consider bone mineral density monitoring during the therapy.
  • One of the most frequently reported adverse reactions in clinical studies is hypercholesterolemia. Consider cholesterol monitoring.
  • Since fatigue, dizziness and somnolence has been reported uncommonly, caution is advised when driving or using machines.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category X (US). Letrozole is contraindicated in women who are or may become pregnant. Studies in animals have shown reproductive toxicity. If Letrozole is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and potential risk for pregnancy loss.
  • Nursing Mothers: It is not known if letrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from letrozole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

[edit] SIDE EFFECTS

Letrozole is generally well tolerated, most common adverse effects include:

  • Hot flushes and increased sweating
  • Hypercholesterolemia
  • Pain in bones and joints (arthralgia)
  • Fatigue

Other possible side effects:

  • Nausea
  • Headache
  • Vaginal dryness (Vaginal moisturisers or lubricants can be helpful)
  • Insomnia
  • Hair loss. this side effect is usually mild and the hair grows back at the end of treatment.
  • Vaginal bleeding
  • Risk of osteoporosis. Letrozole increases the risk of fracture compared with tamoxifen.

Letrozole is not associated with the estrogen-like adverse/benefit effects of tamoxifen (Tamoxifen blocks the effects of estrogen in breast tissue BUT ACTS LIKE ESTROGEN AGONIST in the uterus and bone: Tamoxifen has been associated with endometrial hyperplasia, fibroids, polyps, and endometrial tumors and may INCREASE bone density)

[edit] RELATED LINKS

Infertility: Clomiphene Versus Letrozole

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/22031258
  2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135533/