1. Clinical Overview
Letrozole is a potent, selective, non-steroidal, third-generation aromatase inhibitor. It is a first-line endocrine therapy for hormone receptor-positive (HR+) breast cancer in postmenopausal women. It works by inhibiting the aromatase enzyme, which is responsible for the conversion of androgens to estrogens, thereby significantly reducing systemic estrogen levels. In the Indian context, it is a cornerstone of adjuvant and metastatic treatment for HR+ breast cancer and is also widely used for ovulation induction in anovulatory infertility, particularly in women with Polycystic Ovary Syndrome (PCOS).
| Onset | Duration | Bioavailability |
|---|---|---|
| Pharmacological effect begins within hours, but clinical/endocrine response (estradiol suppression) is typically observed within 24-48 hours. Maximal estradiol suppression occurs within 2-3 days of continuous dosing. | The pharmacological effect persists for the duration of dosing. Estradiol levels return to baseline approximately 3-6 days after discontinuation. | Approximately 99.9%. |
2. Mechanism of Action
Letrozole is a competitive, reversible inhibitor of the aromatase enzyme complex (cytochrome P450 heme protein, CYP19). It binds to the heme moiety of the aromatase enzyme, blocking the conversion of androstenedione and testosterone to estrone and estradiol, respectively. This leads to a profound reduction in circulating estrogen levels in all tissues, depriving estrogen-dependent breast cancer cells of their primary growth stimulus.
3. Indications & Uses
- Adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women.
- First-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer in postmenopausal women.
- Ovulation induction in anovulatory women with Polycystic Ovary Syndrome (PCOS) or other causes of anovulation (using the 5mg dose for a limited duration).
4. Dosage & Administration
Adult Dosage: Breast Cancer: 2.5 mg orally once daily, with or without food. Infertility (Ovulation Induction): 2.5 mg to 5.0 mg (as per this monograph) orally once daily, starting on day 3-5 of menstrual cycle (spontaneous or induced) for 5 days. Dose may be adjusted in subsequent cycles based on response. Treatment beyond 3-4 cycles per indication is not recommended without re-evaluation.
Administration: Take tablet whole with a glass of water, at approximately the same time each day. Can be taken with or without food. For infertility, timing relative to menstrual cycle is critical. Missed dose: If forgotten, take as soon as remembered unless it is almost time for the next dose. Do not double the dose.
5. Side Effects
Common side effects may include:
- Hot flashes (flushing)
- Fatigue/asthenia
- Arthralgia (joint pain) / Myalgia (muscle pain)
- Headache
- Nausea
- Increased sweating
- Peripheral edema
- Hypercholesterolemia (increased LDL)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Tamoxifen | Co-administration reduces letrozole plasma levels by ~38%. Avoid concomitant use. | Major |
| Estrogen-containing therapies (HRT, contraceptives) | May counteract the therapeutic effect of letrozole. Contraindicated. | Major |
| CYP2A6 and CYP3A4 inducers (e.g., Rifampicin, Phenytoin, Carbamazepine) | May decrease letrozole plasma concentrations, reducing efficacy. | Moderate |
| CYP2A6 and CYP3A4 inhibitors (e.g., Ketoconazole, Cimetidine) | May increase letrozole plasma concentrations, potentially increasing toxicity. | Moderate |
| Warfarin | Cases of increased INR reported. Monitor INR closely when starting or stopping letrozole. | Moderate |
7. Patient Counselling
- DO take the tablet at the same time each day to maintain steady levels.
- DO inform all your doctors (including dentists) that you are taking letrozole.
- DO use effective non-hormonal contraception (barrier methods, copper-T) if you are of childbearing potential.
- DO NOT take if you are pregnant or planning to become pregnant without discussing with your oncologist/fertility specialist.
- DO NOT take any estrogen-containing products (HRT, creams, birth control pills).
- DO NOT start any new medication, including OTC or herbal supplements, without consulting your doctor.
8. Toxicology & Storage
Overdose: Expected symptoms would be an extension of its pharmacological effects and side effects: severe dizziness, severe fatigue, severe hot flashes, severe joint pain, and potentially severe gastrointestinal disturbances. No specific experience with acute overdose in humans.
Storage: Store below 30°C. Protect from light and moisture. Keep the tablet in the original blister pack or container until use. Keep out of reach of children.