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. It is a cornerstone of adjuvant and metastatic treatment in the Indian oncology setting.
Adult: 2.5 mg orally once daily, with or without food. Treatment duration for adjuvant therapy is typically 5 years, or up to 10 years in some protocols.
Note: Tablet should be swallowed whole with a glass of water. Can be taken at any time of day, but preferably at the same time each day. If a dose is missed, it should be taken 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, depriving estrogen-dependent (ER+) breast cancer cells of their primary growth stimulus.
Pregnancy: Pregnancy Category X. Letrozole can cause fetal harm. It is contraindicated in pregnancy. It may impair fertility. Women of childbearing potential must use effective non-hormonal contraception during therapy and for at least 3 weeks after discontinuation.
Driving: Patients should be cautioned that letrozole may cause dizziness, fatigue, and somnolence, which could impair the ability to drive or operate machinery.
| Tamoxifen | Co-administration reduces letrozole plasma levels by ~38%. Avoid concomitant use. | Major |
| Estrogen-containing therapies (HRT, contraceptives) | May counteract the pharmacological effect of letrozole. Contraindicated. | Major |
| CYP2A6 and CYP3A4 inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | May decrease letrozole plasma concentrations, potentially reducing efficacy. | Moderate |
| CYP2A6 and CYP3A4 inhibitors (e.g., Cimetidine, Ketoconazole) | May increase letrozole plasma concentrations, potentially increasing toxicity. Clinical significance is limited. | Minor |