Letrozole:

1. Introduction

Letrozole is a non-steroidal aromatase inhibitor primarily used in the treatment of hormone receptor-positive breast cancer in postmenopausal women. By inhibiting aromatase, letrozole reduces oestrogen production, which can slow or stop the growth of oestrogen-dependent tumours. It is also used off-label for ovulation induction in infertility treatments.

2. Indications

  • Approved Indications:
    • Hormone receptor-positive early breast cancer (adjuvant therapy).
    • Advanced or metastatic hormone receptor-positive breast cancer.
    • Extended adjuvant treatment in postmenopausal women following tamoxifen therapy.
  • Off-Label Uses:
    • Ovulation induction in women with polycystic ovary syndrome (PCOS) or unexplained infertility.

3. Dosage

  • Breast Cancer:
    • Early Breast Cancer: 2.5 mg orally once daily for 5 years or as directed.
    • Metastatic Breast Cancer: 2.5 mg orally once daily until disease progression.
  • Ovulation Induction (Off-Label):
    • 2.5–7.5 mg orally once daily for 5 days, starting on day 3 or 5 of the menstrual cycle.

4. Administration

  • Take orally with or without food, preferably at the same time each day.

5. Forms Available

  • Tablets: 2.5 mg.

6. Side Effects

6.1. Common Side Effects

  • Hot flashes.
  • Fatigue.
  • Nausea.
  • Arthralgia (joint pain).

6.2. Less Common Side Effects

  • Headache.
  • Dizziness.
  • Increased sweating.
  • Hair thinning or loss.

6.3. Rare but Serious Side Effects

  • Osteoporosis or bone fractures.
  • Liver enzyme elevation.
  • Cardiovascular events (e.g., deep vein thrombosis, stroke).

7. Warnings

  • Bone Density: Long-term use may cause bone loss (osteopenia or osteoporosis). Regular bone density monitoring is advised.
  • Cardiovascular Risks: Use cautiously in patients with pre-existing cardiovascular disease, as letrozole may increase the risk of thromboembolic events.
  • Liver Impairment: Monitor liver function during prolonged use.

8. Precautions

  • Avoid use in premenopausal women, except for ovulation induction under specialist care.
  • Use cautiously in patients with a history of osteoporosis or fractures.
  • Patients should report symptoms of blood clots, such as leg swelling or chest pain, immediately.

9. Interactions

  • Drug-Drug Interactions:
    • Tamoxifen: May reduce the effectiveness of letrozole. Avoid concurrent use.
    • Oestrogen-containing products: Counteracts the effects of letrozole.
    • CYP2A6 and CYP3A4 inducers (e.g., phenytoin, rifampin): May reduce letrozole levels.
  • Drug-Food Interactions:
    • No significant interactions, but consistency in administration is recommended.

10. Monitoring Parameters

  • For breast cancer: Regular monitoring of tumour progression (e.g., imaging and tumour markers).
  • For ovulation induction: Follicular development using ultrasound and hormonal levels (e.g., oestradiol).
  • Bone density (for long-term therapy).
  • Liver function tests (during prolonged treatment).

11. Use in Children

  • Not recommended due to lack of safety and efficacy data.

12. Use in Pregnancy

  • Category X: Contraindicated in pregnancy due to the risk of foetal harm. It is not to be used in pregnant or breastfeeding women.

13. Use in Elderly

  • Safe for use, but monitor for side effects such as bone loss and cardiovascular risks.

14. Use in Kidney Disease

  • No dose adjustment is required in mild to moderate renal impairment. Use cautiously in severe renal impairment (creatinine clearance <10 mL/min).

15. Use in Liver Disease

  • Use with caution in patients with moderate to severe hepatic impairment. Monitor liver function regularly.

16. Patient Counselling Points

  • Take letrozole at the same time each day to maintain consistent blood levels.
  • Notify your doctor if you experience symptoms like bone pain, severe fatigue, or chest pain.
  • For women using letrozole for ovulation induction, monitor closely for signs of ovarian hyperstimulation (e.g., abdominal pain or swelling).
  • Avoid pregnancy while on letrozole. Use effective contraception during and after therapy until cleared by your doctor.
  • Maintain a diet rich in calcium and vitamin D and consider weight-bearing exercises to reduce the risk of bone loss.

17. Table of Brand Names, Manufacturers, and Prices

Brand NameManufacturerPrice (USD)
FemaraNovartis$250–400 (30 tablets, 2.5 mg)
Generic LetrozoleVarious manufacturers$15–50 (30 tablets, 2.5 mg)

18. FAQs (15 Questions)

  1. What is letrozole used for?
    Letrozole is used to treat hormone receptor-positive breast cancer and for ovulation induction in infertility.
  2. How does letrozole work?
    It inhibits aromatase, reducing oestrogen production and slowing the growth of oestrogen-dependent tumours.
  3. When should I take letrozole?
    Take it once daily, at the same time each day, with or without food.
  4. Can letrozole cause side effects?
    Yes, common side effects include hot flashes, fatigue, and joint pain.
  5. Is letrozole safe during pregnancy?
    No, it is contraindicated due to the risk of foetal harm.
  6. How long should letrozole be taken for breast cancer?
    Typically, it is taken for 5 years, but duration may vary based on the patient’s condition.
  7. Can letrozole cause bone loss?
    Yes, long-term use may cause bone thinning or osteoporosis.
  8. What should I do if I miss a dose of letrozole?
    Take it as soon as you remember, unless it is close to the next dose. Do not double up.
  9. Does letrozole interact with tamoxifen?
    Yes, tamoxifen may reduce the effectiveness of letrozole. Avoid concurrent use.
  10. Can letrozole be used in premenopausal women?
    Generally no, except under specialist care for ovulation induction.
  11. How is letrozole used for ovulation induction?
    It is typically taken for 5 days starting on day 3 or 5 of the menstrual cycle to stimulate ovulation.
  12. Can letrozole cause cardiovascular problems?
    Yes, it may increase the risk of thromboembolic events and cardiovascular issues, especially in those with pre-existing conditions.
  13. How should letrozole be stored?
    Store at room temperature, away from moisture and heat.
  14. What dietary changes are recommended while taking letrozole?
    Increase calcium and vitamin D intake to counteract potential bone loss.
  15. Can letrozole be stopped abruptly?
    Stopping without medical advice is not recommended. Consult your doctor before discontinuation.