Letrozole

The growth of some cancers of the breast is stimulated or maintained by estrogens. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents).

• Letrozole tablet is an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer ( 1.1 ) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy ( 1.2 ) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer ( 1.3 ) 1.1 Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. 1.2 Extended Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy.ICD-10: C50.919

• Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ( 8.1 )] . Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ( 8.1 )] .contraindicated

Letrozole tablets are taken orally without regard to meals ( 2 ): Recommended dose: 2.5.mg once daily ( 2.1 ) Patients with cirrhosis or severe hepatic impairment: 2.5 mg every other day ( 2.5 , 5.3 ) 2.1 Recommended Dose The recommended dose of letrozole tablet is one 2.5 mg tablet administered once a day, without regard to meals. 2.2 Use in Adjuvant Treatment of Early Breast Cancer In the adjuvant setting, the optimal duration of treatment with letrozole is unknown. In both the adjuvant study and the post approval adjuvant study, median treatment duration was 5 years. Treatment should be discontinued at relapse [see Clinical Studies ( 14.1 )]. 2.3 Use in Extended Adjuvant Treatment of Early Breast Cancer In the extended adjuvant setting, the optimal treatment duration with letrozole tablet is not known. The planned duration of treatment in the study was 5 years. In the final updated analysis, conducted at a median follow-up of 62 months, the median treatment duration for letrozole tablets was 60 months. Seventy-one (71%) percent of patients were treated for at least 3 years and 58% of patients completed at least 4.5 years of extended adjuvant treatment. The treatment should be discontinued at tumor relapse [see Clinical Studies ( 14.2 )]. 2.4 Use in First and Second-Line Treatment of Advanced Breast Cancer In patients with advanced disease, treatment with letrozole tablets should continue until tumor progression is evident [see Clinical Studies ( 14.4 , 14.5 )] .

Decreases in bone mineral density may occur. Consider bone mineral density monitoring ( 5.1 ) Increases in total cholesterol may occur. Consider cholesterol monitoring. ( 5.2 ) Fatigue, dizziness and somnolence may occur. Exercise caution when operating machinery ( 5.4 ) Embryo-Fetal toxicity: Can cause fetal harm when administered to pregnant women. Obtain a pregnancy test in females of reproductive potential. Advise females of reproductive potential to use effective contraception ( 5.6 , 8.1 , 8.3 ) 5.1 Bone Effects Use of letrozole may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Results of a safety study to evaluate safety in the adjuvant setting comparing the effect on lumbar spine (L2-L4) BMD of adjuvant treatment with letrozole to that with tamoxifen showed at 24 months a median decrease in lumbar spine BMD of 4.1% in the letrozole arm compared to a median increase of 0.3% in the tamoxifen arm (difference = 4.4%) ( P <0.0001) [see Adverse Reactions ( 6 )] . Updated results from the BMD substudy (MA-17B) in the extended adjuvant setting demonstrated that at 2 years patients receiving letrozole had a median decrease from baseline of 3.8% in hip BMD compared to a median decrease of 2.0% in the placebo group. The changes from baseline in lumbar spine BMD in letrozole and placebo treated groups were not significantly different [see Adverse Reactions ( 6 )].

The following adverse reactions are discussed in greater detail in other sections of the labeling. Bone effects [see Warnings and Precautions ( 5.1 )] Increases in cholesterol [see Warnings and Precautions ( 5.2 )] Fatigue and Dizziness [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (greater than 20%) were hot flashes, arthralgia; flushing, asthenia, edema, arthralgia, headache, dizziness, hypercholesterolemia, sweating increased, bone pain and musculoskeletal ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Treatment of Early Breast Cancer In study, BIG 1-98, the median treatment duration of adjuvant treatment was 60 months and the median duration of follow-up for safety was 96 months for patients receiving letrozole and tamoxifen. Certain adverse reactions were prospectively specified for analysis (see Table 1), based on the known pharmacologic properties and side effect profiles of the two drugs. Adverse reactions were analyzed irrespective of whether a symptom was present or absent at baseline.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on postmarketing reports, findings from animal studies and the mechanism of action, letrozole can cause fetal harm and is contraindicated for use in pregnant women. In post-marketing reports, use of letrozole during pregnancy resulted in cases of spontaneous abortions and congenital birth defects; however, the data are insufficient to inform a drug-associated risk [see Contraindications ( 4 ), Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.2 ) and Clinical Pharmacology ( 12.1 )]. In animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorption, fewer live fetuses, and fetal malformation affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily maximum recommended human dose (MRHD) on a mg/m 2 basis (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Metabolism

Absorption and Distribution: Letrozole is rapidly and completely absorbed from the gastrointestinal tract and absorption is not affected by food. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway.

Isolated cases of letrozole overdose have been reported. In these instances, the highest single dose ingested was 62.5 mg or 25 tablets. While no serious adverse reactions were reported in these cases, because of the limited data available, no firm recommendations for treatment can be made. However, emesis could be induced if the patient is alert. In general, supportive care and frequent monitoring of vital signs are also appropriate. In single-dose studies, the highest dose used was 30 mg, which was well tolerated; in multiple-dose trials, the largest dose of 10 mg was well tolerated. Lethality was observed in mice and rats following single oral doses that were equal to or greater than 2,000 mg/kg (about 4,000 to 8,000 times the daily maximum recommended human dose on a mg/m 2 basis); death was associated with reduced motor activity, ataxia and dyspnea. Lethality was observed in cats following single IV doses that were equal to or greater than 10 mg/kg (about 50 times the daily maximum recommended human dose on a mg/m 2 basis); death was preceded by depressed blood pressure and arrhythmias.

• Jul 25, 1997NDANDA020726Novartis Pharms
• Jun 3, 2011ANDAANDA091191Carnegie
• Jun 3, 2011ANDAANDA200161Natco Pharma Ltd
• Jun 3, 2011ANDAANDA090289Teva Pharms
• Jun 3, 2011ANDAANDA090934Accord Hlthcare
• May 4, 2017NDANDA209935Novartis
• Nov 14, 2018ANDAANDA205869Beijing Yiling
• Jan 11, 2019ANDAANDA211717Eugia Pharma

1. 1Fatigue7,34112%
2. 2Nausea5,4098.9%
3. 3Neutropenia5,0188.3%
4. 4Diarrhoea4,6017.6%
5. 5Malignant Neoplasm Progression4,3897.2%
6. 6Arthralgia3,8936.4%
7. 7White Blood Cell Count Decreased3,7756.2%
8. 8Alopecia3,6496.0%
9. 9Pain3,0095.0%
10. 10Asthenia2,9294.8%
11. 11Dyspnoea2,9034.8%
12. 12Neoplasm Progression2,7964.6%
13. 13Vomiting2,7454.5%
14. 14Death2,6754.4%
15. 15Headache2,4514.0%

Recent PubMed references pinned to Letrozole as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Comparative efficacy of modified antagonist protocols combining clomiphene citrate or letrozole for ovarian stimulation in patients with normal ovarian reserve.
  Frontiers in endocrinology · 2026 · Wei H, Lin H, Cai L, et al.
  PMID 42130742DOI 10.3389/fendo.2026.1814317
• Alginate-functionalized and PEGylated niosomes co-encapsulating letrozole and berberine for preclinical breast cancer therapy: Overcoming multidrug resistance.
  International journal of biological macromolecules · 2026 · Velashjerdi Z, Ghafouri H, Noorbazargan H, et al.
  PMID 42069205DOI 10.1016/j.ijbiomac.2026.152333
• Gonadotropin-releasing hormone agonist (GnRH-a) pretreatment duration and letrozole supplementation for optimizing live birth rates in women with adenomyosis undergoing frozen-thawed embryo transfer (GOLD-FET): study protocol for a multicenter, 2 × 2 factorial randomized controlled trial in China.
  Trials · 2026 · Xiong Y, Gu F, Du L, et al.
  PMID 42032741DOI 10.1186/s13063-026-09731-2
• Oestradiol concentration on ovulatory trigger day and live births in letrozole-stimulated frozen embryo transfer cycles.
  Reproductive biomedicine online · 2026 · Yeshua A, Flannagan K, Romanski P, et al.
  PMID 41980564DOI 10.1016/j.rbmo.2026.105631
• Letrozole for Ovulation Induction in Women With Polycystic Ovary Syndrome.
  Obstetrical & gynecological survey · 2026 · Li XL
  PMID 41950500DOI 10.1097/OGX.0000000000001494
• Modified letrozole vs GnRH antagonist protocols in ovarian aging women for IVF: an open-label, multicenter, randomized controlled trial.
  Nature communications · 2026 · Zhao Y, Zhao S, Xu J, et al.
  PMID 41862492DOI 10.1038/s41467-026-70964-5
• Protective Effects of Hesperidin on Letrozole-Induced Neurotoxicity: Involvement of Oxidative Stress, Apoptotic Signaling, and Inflammation.
  Journal of biochemical and molecular toxicology · 2026 · Ayhan İ, Kaplan MN, Kasim DD, et al.
  PMID 41817870DOI 10.1002/jbt.70777
• Targeted management of adenomyosis: frozen embryo transfer outcomes with GnRH-agonist and letrozole therapy: a case series.
  Journal of medical case reports · 2026 · Mojtahedi MF, Melado L, Edades J, et al.
  PMID 41803932DOI 10.1186/s13256-026-05907-1

The 10 most recently updated of 876 ClinicalTrials.gov registrations naming Letrozole as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Clinical Study of HRS-6209 Combined With Other Treatment Regimens in Patients With Breast Cancer
  Recruiting · Phase 1 · Phase 2 · Interventional · 80 enrolled · Jiangsu HengRui Medicine Co., Ltd.
  NCT06974929updated 2026-06-12
• A Trial of HRS-6209-205 to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HRS-6209 in Combination Therapy in Subjects With HR-Positive/HER2-Negative Cancer
  Recruiting · Phase 1 · Interventional · 15 enrolled · Atridia Pty Ltd.
  NCT07358377updated 2026-06-12
• Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
  Recruiting · Phase 3 · Interventional · 1,978 enrolled · National Cancer Institute (NCI)
  NCT07391774updated 2026-06-12
• Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)
  Active not recruiting · Phase 3 · Interventional · 10,273 enrolled · National Cancer Institute (NCI)
  NCT00310180updated 2026-06-11
• Neoadjuvant Dalpiciclib + AI → SHR-A1811 for HR+/HER2-Low Breast Cancer
  Not yet recruiting · Phase 2 · Interventional · 20 enrolled · Tang-Du Hospital
  NCT07618923updated 2026-06-11
• Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer
  Active not recruiting · Phase 3 · Interventional · 5,018 enrolled · National Cancer Institute (NCI)
  NCT01272037updated 2026-06-11
• Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 255 enrolled · Novartis Pharmaceuticals
  NCT01872260updated 2026-06-11
• Roll-over Study to Allow Continued Access to Ribociclib
  Active not recruiting · Phase 4 · Interventional · 134 enrolled · Novartis Pharmaceuticals
  NCT05161195updated 2026-06-11
• Reversing InGuinal Hernia Trial: The Evaluation of Sex Hormones to Reverse Inguinal Hernias in Males
  Not yet recruiting · Phase 1 · Interventional · 30 enrolled · Northwestern University
  NCT07604272updated 2026-06-11
• To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer
  Active not recruiting · Phase 1 · Interventional · 200 enrolled · Genentech, Inc.
  NCT03006172updated 2026-06-10

Frequently asked questions

How does Letrozole work?

The growth of some cancers of the breast is stimulated or maintained by estrogens. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents).

What is Letrozole used for?

According to FDA labeling, Letrozole carries indications including: Letrozole tablet is an aromatase inhibitor indicated for: Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer ( 1.1 ) Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy ( 1.2 ) First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer ( 1.3 ) 1.1 Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. 1.2 Extended Adjuvant Treatment of Early Breast Cancer Letrozole tablets are indicated for the extended adjuvant treatment of early breast cancer in postmenopausal women, who have received 5 years of adjuvant tamoxifen therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Letrozole?

Letrozole is classified as Aromatase inhibitors, Aromatase Inhibitor, Aromatase Inhibitors, Enzyme Inhibitors, Decreased Ovarian Estrogen Secretion.

What are the brand names for Letrozole?

Letrozole is marketed under brand names including Femara.

What are the contraindications for Letrozole?

Letrozole labeling lists contraindications including: Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ( 8.1 )] . Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations ( 8.1 )] .. Always consult the full prescribing information and a clinician.