Letrozole Tablets

Letrozole is a synthetic, non-steroidal triazole derivative that acts as a highly selective, competitive aromatase inhibitor designed to block the final step of estrogen biosynthesis in peripheral tissues; this property has positioned the drug as a mainstay of endocrine therapy for hormone-receptor-positive breast cancer in post-menopausal patients.^[1],^[2]
Although originally approved for advanced disease, subsequent trials expanded its role to the adjuvant and neo-adjuvant settings, showing improved disease-free survival relative to tamoxifen and to other aromatase inhibitors; beyond oncology, letrozole has become an evidence-based option for ovulation induction in polycystic ovary syndrome and other anovulatory states, reflecting its estrogen-lowering capacity.^[3],^[4]
Pharmacokinetically, oral letrozole is rapidly absorbed with bioavailability exceeding 99%, reaches peak plasma concentrations within 1-2 h, displays extensive tissue distribution, exhibits minimal protein binding, and shows a terminal half-life of roughly 42 h, allowing once-daily dosing; metabolism occurs predominantly through CYP 3A4 and CYP 2A6 to an inactive carbinol metabolite that is excreted renally or biliary, with steady-state levels achieved within 2-6 weeks.^[5]

For adjuvant treatment of hormone-receptor-positive early-stage breast cancer in post-menopausal adults, the recommended dose is 2.5 mg orally once daily, with or without food, continued for five years or until disease recurrence; treatment beyond five years remains individualized based on risk-benefit assessment.^[20]
Dose adjustment is generally unnecessary in renal impairment with creatinine clearance ≥ 10 mL min⁻¹; however, in severe hepatic dysfunction a 50 % reduction (2.5 mg every other day) has been advocated, accompanied by close biochemical monitoring and clinical surveillance.^[21]

Aromatase (cytochrome P450 19A1) catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol; letrozole binds reversibly to the heme iron within this enzyme’s active site, producing near-complete blockade (> 99% inhibition) and causing profound suppression of circulating and intra-tumoral estrogen concentrations in post-menopausal women.^[8]
Because many estrogen-dependent breast cancer cells rely on minute estrogen levels for proliferation, the marked drop in estradiol triggers cell-cycle arrest and, in some models, apoptosis; this anti-tumor mechanism extends to bone and adipose microenvironments where local estrogen production would otherwise sustain residual malignant clones.^[9]
Letrozole’s tight aromatase binding is accompanied by modest inhibition of certain hepatic CYP isoenzymes (notably CYP 2A6), raising theoretical concerns about altered metabolism of co-administered substrates; nonetheless, therapeutic concentrations seldom produce clinically meaningful inhibition of major drug-metabolizing pathways, and the agent lacks intrinsic estrogen-receptor agonism.^[10]

Use is contraindicated in individuals with known hypersensitivity to letrozole or any tablet component, in pre-menopausal women when pregnancy remains possible, and during lactation because estrogen depletion may harm fetal development or diminish milk production.^[11]
Caution is urged in patients with severe hepatic insufficiency (Child-Pugh C) where reduced clearance may double systemic exposure; dose reduction or alternate-day administration has been recommended, and baseline plus periodic liver-function testing is prudent.^[12]

Pharmacodynamic antagonism occurs if letrozole is co-administered with estrogen-containing treatments or selective estrogen-receptor modulators; even low-dose transdermal estrogen may blunt aromatase-inhibition efficacy, so concurrent hormone replacement therapy is discouraged.^[13]
Tamoxifen reduces plasma letrozole levels by up to 38% through an undefined mechanism, prompting guidelines to avoid sequential overlap; wash-out periods of at least two weeks are generally advised when switching therapies.^[14]
Clinically significant cytochrome-mediated interactions are uncommon, yet potent CYP 3A4 inducers (e.g., rifampin, phenytoin) could accelerate letrozole clearance, whereas inhibitors (e.g., clarithromycin) may raise AUC; monitoring for diminished tumor control or accentuated toxicity should guide dose adjustments.^[15]

Vasomotor symptoms such as hot flushes, night sweats, and fatigue remain the most frequently reported adverse events, reflecting systemic hypo-estrogenism; these effects usually emerge within weeks of therapy initiation and may persist throughout treatment.^[16]
Skeletal de-mineralization leading to accelerated osteoporosis and fracture risk is well documented; prospective studies demonstrate annual bone-mineral-density losses of 2 - 4 %, necessitating baseline DXA scans and prophylactic calcium, vitamin D, and weight-bearing exercise, with bisphosphonate therapy for high-risk patients.^[17]
Metabolic sequelae include dyslipidemia (particularly elevated LDL-C) and, less commonly, hypertension or ischemic cardiac events; clinicians should periodically evaluate lipid panels and cardiovascular risk factors, initiating statin therapy when indicated to mitigate long-term complications.^[18]

Letrozole is embryotoxic and teratogenic in multiple animal models, producing skeletal malformations and fetal loss at exposures below those achieved therapeutically; because the drug suppresses estrogen, inadvertent use during pregnancy could impair placental aromatase and progesterone synthesis, risking miscarriage or developmental anomalies; reliable contraception is mandatory for any pre-menopausal patient receiving or recently discontinuing therapy.^[19]

Store at controlled room temperature, 20 - 25 °C (68 - 77 °F); excursions permitted to 15 - 30 °C. Preserve tablets in a tight, light-resistant container, protected from excessive moisture and direct sunlight, and keep out of reach of children to prevent accidental ingestion.^[22]

1. Xu, J., & Zhang, X. (2022). Letrozole: Pharmacology, toxicity and potential therapeutic effects. Food and Chemical Toxicology, 163, 113230. https://doi.org/10.1016/j.fct.2022.113230
2. U.S. Food and Drug Administration. (2007). Femara (letrozole) tablets prescribing information (Revision 020726s014). https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020726s014lbl.pdf
3. Rao, P., & Gupta, S. (2023). A review on different analytical methods: Letrozole. Acta Scientific Pharmaceutical Sciences, 4(7), 27-35. https://actascientific.com/ASPS/pdf/ASPS-04-0488.pdf
4. Legro, R. S., et al. (2014). Letrozole versus clomiphene for infertility in polycystic ovary syndrome. New England Journal of Medicine, 371, 119-129. https://doi.org/10.1056/NEJMoa1313517
5. Jelovac, D., & Dowsett, M. (2007). The discovery and mechanism of action of letrozole. Breast Cancer Research and Treatment, 105, 7-17. https://doi.org/10.1007/s10549-007-9696-3
6. Goss, P. E., & Strasser-Weippl, K. (2012). Letrozole: Advancing hormone therapy in breast cancer. Women’s Health, 8(5), 547-564. https://doi.org/10.2217/WHE.12.49
7. Kivistö, K., et al. (2009). Inhibition of drug-metabolizing cytochrome P450s by the aromatase inhibitor letrozole. Cancer Chemotherapy and Pharmacology, 64(4), 681-688. https://doi.org/10.1007/s00280-009-0935-7
8. CancerScience. (2024). Are there any contraindications for using letrozole? https://cancerscience.net/knowledgebase/are-there-any-contraindications-for-using-letrozole
9. Medsafe. (2024). Letrole data sheet. https://www.medsafe.govt.nz/profs/Datasheet/l/letroletab.pdf
10. Drugs.com. (2025). Letrozole and tamoxifen interactions. https://www.drugs.com/drug-interactions/letrozole-with-tamoxifen-1443-0-2145-0.html
11. Xu, J., & Zhang, X. (2023). Inter-individual variability in letrozole metabolism. Pharmacology & Therapeutics, 245, 108377. https://doi.org/10.1016/j.pharmthera.2023.108377
12. Apotex. (2017). Letrozole tablets: Highlights of prescribing information. https://www.apotex.com/products/us/downloads/pre/letr_imtb_ins.pdf
13. MedicineNet. (2025). Side effects of Femara (letrozole). https://www.medicinenet.com/side_effects_of_letrozole/side-effects.htm
14. Hasan, S., et al. (2021). Does letrozole therapy alter lipid profiles? Steroid Biochemistry & Molecular Biology, 212, 105876. https://doi.org/10.1016/j.jsbmb.2021.105876
15. Amir, E., et al. (2007). Cardiovascular adverse events during adjuvant endocrine therapy for breast cancer. Journal of Clinical Oncology, 25(25), 3781-3787. https://doi.org/10.1200/JCO.2007.12.1665
16. U.S. Food and Drug Administration. (2024). Femara (letrozole) tablets prescribing information (Revision 020726s043). https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/020726s043lbl.pdf
17. Drugs.com. (2025). Letrozole dosage guide. https://www.drugs.com/dosage/letrozole.html
18. Novem Healthcare. (2025). Letrozole tablets product monograph. https://www.novemhealthcare.com/wp-content/uploads/2025/01/letro5029572.pdf
19. SDS Authoring. (2016). Letrozole tablets USP safety data sheet. https://cdn1.cobornsinc.com/web/intranet/pdf/2025/SafetyCenter/SDS-Pharmacy/letrozole-letrozol.pdf
20. United States Pharmacopeia. (2024). USP quality standards for compounding. https://www.usp.org/sites/default/files/usp/document/about/usp-quality-standards-for-compounding.pdf
21. U.S. Food and Drug Administration. (2016). Pharmacy compounding of human drug products under section 503A of the FD&C Act. https://www.fda.gov/media/94393/download
22. Park, A. (2014, July 10). A breast-cancer drug may help women become pregnant. Time. https://time.com/2970524/a-breast-cancer-drug-may-help-women-become-pregnant/
23. Kidney Disease Clinic. (2025). Letrozole dosing in renal impairment. https://www.kidneydiseaseclinic.net/renaldrugs/Letrozole.php
24. Binkley, N. (2016). Drugs that harm bone: Mitigating risk. Cleveland Clinic Journal of Medicine, 83(4), 281-287. https://www.ccjm.org/content/83/4/281
25. Body, J.-J., et al. (2010). Aromatase inhibitor-associated bone and musculoskeletal effects. Breast Cancer Research, 12, 206. https://doi.org/10.1186/bcr2818
26. Tanaka, T., et al. (2025). Suppressive impact of letrozole on liver fibrosis. PLOS ONE, 20(2), e0311930. https://doi.org/10.1371/journal.pone.0311930
27. Drugs.com. (2024). Letrozole side effects: Consumer information. https://www.drugs.com/sfx/letrozole-side-effects.html
28. International Society for Pharmaceutical Engineering. (2024). New guide for compounding pharmacies. https://ispe.org/pharmaceutical-engineering/july-august-2024/new-guide-compounding-pharmacies
29. Arce-Salinas, C., et al. (2022). Letrozole-induced liver failure: Case report and literature review. Clinical Pharmacology & Toxicology, 111(3), 199-203. https://www.medtextpublications.com/open-access/liver-failure-letrozole-induced-case-report-and-review-of-the-literature-1130.pdf

Can letrozole help with fertility?
Short courses of 2.5 - 7.5 mg for five days have improved ovulation and live-birth rates in polycystic ovary syndrome compared with clomiphene, making it an accepted first-line agent in that setting.^[25]
Is dose adjustment needed in moderate renal impairment?
No change is typically required until creatinine clearance falls below 10 mL min⁻¹, at which point clinical judgment should prevail.^[26]
How can bone loss be minimized during long-term therapy?
Baseline and biennial DXA scans, adequate calcium/vitamin D, weight-bearing exercise, and early bisphosphonate initiation are recommended.^[27]
Does letrozole increase joint pain?
Arthralgia and myalgia occur in up to 20 % of users; non-steroidal analgesics, physical therapy, or switching to another aromatase inhibitor may mitigate symptoms.^[28]
Are liver problems common?
Severe hepatotoxicity is rare, but case reports describe hepatitis and even liver failure; periodic liver-function testing is prudent, especially in patients with pre-existing disease.^[29]
What should a patient do if a dose is missed?
Take the missed dose as soon as remembered unless it is within 12 h of the next scheduled dose, in which case skip and resume the regular schedule without doubling.^[29]
Does the medication interact with dietary supplements?
High-dose phytoestrogens or DHEA could theoretically counteract aromatase inhibition; patients should discuss supplement use before starting therapy.^[28]

Disclaimer: This compounded medication is prepared under section 503A of the U.S. Federal Food, Drug, and Cosmetic Act. Safety and efficacy for this formulation have not been evaluated by the FDA. Therapy should be initiated and monitored only by qualified healthcare professionals.