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).
Adult: 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.
Note: 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.
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.
Pregnancy: Pregnancy Category D (US FDA). Teratogenic and fetotoxic in animal studies. Contraindicated in pregnancy. Can cause fetal harm. Women of childbearing potential must use effective non-hormonal contraception during and for at least 3 weeks after treatment. For infertility use, pregnancy must be excluded before starting therapy.
Driving: May cause dizziness, fatigue, and somnolence. Patients should be cautioned about operating machinery or driving until they know how letrozole affects them.
| 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 |