{
 "query": "letrozole",
 "ingredient": "letrozole",
 "slug": "letrozole",
 "rxcui": "72965",
 "brands": [
  "Femara"
 ],
 "names": [
  "letrozole"
 ],
 "classes": [
  {
   "id": "L02BG",
   "name": "Aromatase inhibitors"
  }
 ],
 "alternatives": [
  "aminoglutethimide",
  "anastrozole",
  "exemestane",
  "formestane"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 24
  },
  "boxed_warning": "",
  "indications_and_usage": "Letrozole tablets are 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. The effectiveness of letrozole tablets in extended adjuvant treatment of early breast cancer is based on an analysis of disease-free survival in patients treated with letrozole tablets for a median of 60 months [see Clinical Studies (14.2 , 14.3) ] . 1.3 First and Second-Line Treatment of Advanced Breast Cancer Letrozole tablets are indicated for first-...",
  "contraindications": "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) ] . Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions (6) ] . Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions (6) ] . Pregnancy ( 4 ) Known hypersensitivity to the active substance, or to any of the excipients ( 4 )",
  "warnings_and_cautions": "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 tablets 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 fro...",
  "warnings": "",
  "adverse_reactions": "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 AvKARE, Inc. at 1-855-361-3993 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 tablets and tamoxifen. Certain adverse reactions were pr...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Contraindications ( 4 ) 7/2017 Warnings and Precautions, Embryo-Fetal Toxicity ( 5.6 ) 7/2017",
  "information_for_patients": "Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during letrozole tablets therapy and for at least 3 weeks after the last dose. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with letrozole tablets [see Warnings and Precautions (5.6) and Use in Specific Populations (8.1 , 8.3) ] . Lactation Advise women not to breastfeed during letrozole tablets treatment and for at least 3 weeks after the last dose [see Use in Specific Populations (8.2) ] . Infertility Advise females and males of reproductive potential of the potential for reduced fertility from letrozole tablets [see Use in Specific Populations (8.3) ] . Fatigue and Dizziness Since fatigue and dizziness have been observed with the use of letrozole tablets and somnolence was uncommonly reported, caution is advised when driving or using machinery. Bone Effects Consideration should be given to monitoring bone mineral density.",
  "spl_medguide": "",
  "clinical_studies": "14.1 Updated Adjuvant Treatment of Early Breast Cancer In a multicenter study (BIG 1-98, NCT00004205) enrolling over 8,000 postmenopausal women with resected, receptor-positive early breast cancer, one of the following treatments was randomized in a double-blind manner: Option 1: tamoxifen for 5 years Letrozole tablets for 5 years tamoxifen for 2 years followed by letrozole tablets for 3 years Letrozole tablets for 2 years followed by tamoxifen for 3 years Option 2: tamoxifen for 5 years Letrozole tablets for 5 years The study in the adjuvant setting, BIG 1-98 was designed to answer two primary questions: whether letrozole tablets for 5 years was superior to Tamoxifen for 5 years (Primary Core Analysis) and whether switching endocrine treatments at 2 years was superior to continuing the same agent for a total of 5 years (Sequential Treatments Analysis). Selected baseline characteristics for the study population are shown in Table 6. The primary endpoint of this trial was disease-free survival (DFS) (i.e., interval between randomization and earliest occurrence of a local, regional, or distant recurrence, or invasive contralateral breast cancer, or death from any cause). The secondar...",
  "brand_name": "LETROZOLE",
  "manufacturer": "AvPAK",
  "application_number": "ANDA200161",
  "pharm_class_epc": [
   "Aromatase Inhibitor [EPC]"
  ],
  "route": [
   "ORAL"
  ],
  "effective_time": "20260120",
  "set_id": "93f317f1-96d1-498e-e053-2995a90ac60d",
  "has_boxed_warning": false,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 56889,
  "serious": 45338,
  "death": 5427,
  "hospitalization": 14680,
  "primary_suspect": 56780,
  "top_reactions": [
   [
    "Fatigue",
    7140
   ],
   [
    "Nausea",
    5243
   ],
   [
    "Neutropenia",
    5223
   ],
   [
    "Diarrhoea",
    4509
   ],
   [
    "Malignant Neoplasm Progression",
    4331
   ],
   [
    "White Blood Cell Count Decreased",
    3816
   ],
   [
    "Alopecia",
    3579
   ],
   [
    "Arthralgia",
    3530
   ],
   [
    "Asthenia",
    2828
   ],
   [
    "Neoplasm Progression",
    2784
   ],
   [
    "Pain",
    2723
   ],
   [
    "Dyspnoea",
    2710
   ],
   [
    "Vomiting",
    2607
   ],
   [
    "Death",
    2408
   ],
   [
    "Decreased Appetite",
    2301
   ]
  ],
  "by_year": {
   "2019": 6155,
   "2020": 6240,
   "2021": 6322,
   "2022": 5840,
   "2023": 5922,
   "2024": 5020,
   "2025": 4534,
   "2026": 2069
  },
  "by_year_primary": {
   "2019": 6154,
   "2020": 6239,
   "2021": 6318,
   "2022": 5820,
   "2023": 5884,
   "2024": 5004,
   "2025": 4516,
   "2026": 2059
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [],
 "recall_total": 0,
 "drugsfda": {
  "applications": 23,
  "nda": 1,
  "anda": 20,
  "first_approval": "19970725",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 10,
  "labeling_recent": 1,
  "sponsors": [
   "ACCORD HLTHCARE",
   "ACTAVIS TOTOWA",
   "APOTEX INC",
   "CHARTWELL RX",
   "EUGIA PHARMA",
   "FRESENIUS KABI USA",
   "HIKMA",
   "HIKMA PHARMS"
  ],
  "unapproved": false,
  "first_approval_fmt": "07/25/1997"
 },
 "trials": {
  "total": 904,
  "completed": 388,
  "terminated": 101,
  "with_results": 192,
  "industry": 357,
  "phase3": 202,
  "results_share": 0.4948453608247423,
  "terminated_share": 0.11172566371681415
 },
 "pubmed": {
  "rct": 351,
  "meta": 52,
  "recent_rct": 75,
  "cochrane": [
   {
    "pmid": "36165742",
    "title": "Aromatase inhibitors (letrozole) for ovulation induction in infertile women with polycystic ovary syndrome",
    "year": "2022"
   },
   {
    "pmid": "29797697",
    "title": "Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome",
    "year": "2018"
   },
   {
    "pmid": "24213953",
    "title": "Tamoxifen or letrozole versus standard methods for women with estrogen-receptor positive breast cancer undergoing oocyte or embryo cryopreservation in assisted reproduction",
    "year": "2013"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 0.0,
  "records": 0,
  "by_name": [],
  "names_checked": [
   "letrozole",
   "Femara"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 861594,
  "beneficiaries": 213759,
  "spend": 20503395.1,
  "by_brand": [
   {
    "brand": "Letrozole",
    "claims": 860689,
    "per_claim": 22.299198282,
    "is_generic": true
   },
   {
    "brand": "Femara",
    "claims": 905,
    "per_claim": 1448.3098674,
    "is_generic": false
   }
  ],
  "per_claim": 23.797049538413685
 },
 "mdl": [],
 "dsc": [],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": true,
  "status": "AddedToEml",
  "name": "letrozole",
  "matched": "letrozole",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 11579,
  "fills": 861594,
  "per_million": 13439.04437588934,
  "ratio": 4.853480767389335,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 86,
   "letter": "B",
   "why": [
    "13,439 FDA reports naming it as the suspect drug per million Medicare fills, 4.9x the median drug on this site (-14)",
    "Death share in reports is near or below the FAERS average (1.0x)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 72,
   "letter": "C",
   "why": [
    "351 randomized trials and 52 systematic reviews/meta-analyses indexed in PubMed",
    "On the WHO Model List of Essential Medicines (shown for context; no score effect)",
    "3 independent Cochrane review(s) exist",
    "Only 49% of completed registered trials posted results (-8)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 95,
   "letter": "A",
   "why": [
    "No recalls on record since 2016",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $0 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 100,
   "letter": "A",
   "why": [
    "Generic versions approved (20 applications)",
    "4 same-class alternatives exist"
   ],
   "weight": 0.1
  }
 },
 "total": 87,
 "grade": "B",
 "questions": [
  "The most-reported problems in FDA's adverse event data are fatigue, nausea, neutropenia, diarrhoea. How would we recognize and handle those?",
  "Why this one over aminoglutethimide, anastrozole, exemestane? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}