Letrozole exerts its therapeutic effects by inhibiting the enzyme aromatase, which is responsible for converting androgens (male hormones) into estrogens (female hormones) in peripheral tissues. This mechanism is particularly important in postmenopausal women, where the ovaries no longer produce estrogen, and peripheral aromatization becomes the primary source of estrogen.

1. Aromatase Inhibition:
   • Letrozole binds reversibly to the aromatase enzyme, preventing the conversion of androgens (such as androstenedione and testosterone) into estrogens (estrone and estradiol).
   • This leads to a significant reduction in circulating estrogen levels, which is beneficial in estrogen-dependent breast cancer.
2. Estrogen Suppression:
   • By lowering estrogen levels, letrozole inhibits the growth of hormone receptor-positive breast cancer cells that rely on estrogen for proliferation.
3. Ovulation Induction:
   • In fertility treatments, letrozole temporarily reduces estrogen levels, which stimulates the pituitary gland to release more follicle-stimulating hormone (FSH). This promotes the development of ovarian follicles and induces ovulation.

Letrozole is primarily used for the following conditions:

1. Breast Cancer Treatment:
   • Adjuvant Therapy: Used after surgery or other primary treatments to reduce the risk of cancer recurrence in postmenopausal women with hormone receptor-positive breast cancer.
   • Metastatic Breast Cancer: Used to treat advanced or metastatic breast cancer in postmenopausal women.
   • Neoadjuvant Therapy: Administered before surgery to shrink large tumors and make them more operable.
2. Ovulation Induction:
   • Used off-label to treat infertility in women with polycystic ovary syndrome (PCOS) or other ovulatory disorders.
3. Extended Adjuvant Therapy:
   • Used after completing 5 years of tamoxifen therapy to further reduce the risk of cancer recurrence.

The dosage of letrozole varies depending on the condition being treated. Always follow the prescribing physician's instructions.

Common Dosages:

• Breast Cancer: 2.5 mg orally once daily, with or without food. Treatment duration may range from 5 to 10 years, depending on the clinical scenario.
• Ovulation Induction: 2.5–5 mg orally once daily for 5 days, starting on day 3–5 of the menstrual cycle.

Administration Tips:

• Take the medication at the same time each day to maintain consistent levels in the body.
• Do not crush or chew the tablet; swallow it whole with water.
• For fertility treatment, follow the specific instructions provided by your fertility specialist.

Letrozole is generally well-tolerated, but some patients may experience side effects. These can include:

Common Side Effects:

• Hot flashes
• Fatigue
• Joint or muscle pain
• Headache
• Nausea
• Sweating
• Bone pain or osteoporosis (due to reduced estrogen levels)

Rare but Serious Side Effects:

• Signs of blood clots (e.g., leg pain, chest pain, shortness of breath)
• Severe allergic reactions (rash, itching, swelling, difficulty breathing)
• Liver dysfunction (e.g., jaundice, dark urine, abdominal pain)
• Cardiovascular events (e.g., heart attack, stroke)

If any severe side effects occur, discontinue use and seek medical attention immediately.

Before using letrozole, inform your healthcare provider if you have:

• A history of osteoporosis or bone disorders
• Liver or kidney disease
• Cardiovascular disease
• High cholesterol levels
• Allergies to letrozole or any of its components

Special Populations:

• Pregnancy: Letrozole is contraindicated during pregnancy as it may harm the fetus. It is classified as Pregnancy Category D.
• Breastfeeding: Letrozole is not recommended for use during breastfeeding.
• Elderly Patients: Use with caution due to the potential for increased side effects, particularly bone loss and cardiovascular risks.

Letrozole may interact with other medications, altering their effectiveness or increasing the risk of side effects. Notable interactions include:

1. Tamoxifen:
   • Concurrent use with tamoxifen may reduce the efficacy of letrozole.
2. Estrogen-Containing Therapies:
   • Estrogen-containing medications (e.g., hormone replacement therapy) may counteract the effects of letrozole.
3. CYP2A6 and CYP3A4 Inducers:
   • Drugs like rifampicin and phenytoin may reduce letrozole levels by increasing its metabolism.
4. Bisphosphonates:
   • Used to prevent bone loss in patients on long-term letrozole therapy.
5. Warfarin:
   • Letrozole may increase the risk of bleeding when used with anticoagulants like warfarin.

Always inform your healthcare provider about all medications, supplements, and herbal products you are taking.

Generic Names in Pharmacy

• Letrozole (the active ingredient in Femara)