{
 "query": "estradiol",
 "ingredient": "estradiol",
 "slug": "estradiol",
 "rxcui": "4083",
 "brands": [
  "Yuvafem",
  "Dotti",
  "Estring",
  "Imvexxy",
  "Lyllana",
  "Climara",
  "Femring",
  "Vagifem",
  "Estrace",
  "Estrogel",
  "Depo-estradiol",
  "Minivelle",
  "Divigel",
  "Evamist",
  "Menostar",
  "Elestrin",
  "Delestrogen",
  "Alora",
  "Vivelle"
 ],
 "names": [
  "estradiol",
  "estradiol 3-benzoate",
  "estradiol acetate",
  "estradiol cypionate",
  "estradiol hemihydrate",
  "estradiol valerate"
 ],
 "classes": [
  {
   "id": "G03CA",
   "name": "Natural and semisynthetic estrogens, plain"
  }
 ],
 "alternatives": [
  "chlorotrianisene",
  "estetrol",
  "estriol",
  "estrogens, conjugated (usp)",
  "estrone",
  "ethinyl estradiol",
  "promestriene"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 86,
   "TRANSDERMAL": 39,
   "VAGINAL": 32,
   "TOPICAL": 18,
   "INTRAMUSCULAR": 5
  },
  "boxed_warning": "ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of \u201cnatural\u201d estrogens results in a different endometrial risk profile than \u201csynthetic\u201d estrogens at equivalent estrogen doses. (See WARNINGS, Malignant neoplasms, Endometrial cancer .) CARDIOVASCULAR AND OTHER RISKS Estrogens with or without progestins should not be used for the prevention of cardiovascular disease. (See WARNINGS, Cardiovascular disorders .) The Women\u2019s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (See CLINICAL PHARMACOLOGY, Clinical Studies . ) The Women\u2019s Health Initiative Memory Study (WHIMS), a substudy of WH...",
  "indications_and_usage": "INDICATIONS AND USAGE Estradiol tablets are indicated in the: Treatment of moderate to severe vasomotor symptoms associated with the menopause. Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease. Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Prevention of osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered to be appropriate. (See CLINICAL PHARMACOLOGY , Clinical Studies . ) The mainstays for decreasing the risk of postmenopausal osteoporosis are weight bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average ...",
  "contraindications": "CONTRAINDICATIONS Estrogens should not be used in individuals with any of the following conditions: Undiagnosed abnormal genital bleeding. Known, suspected or history of cancer of the breast except in appropriately selected patients being treated for metastatic disease. Known or suspected estrogen-dependent neoplasia. Active deep vein thrombosis, pulmonary embolism or history of these conditions. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction. Liver dysfunction or disease. Estradiol tablets should not be used in patients with known hypersensitivity to its ingredients. Estradiol tablets 2 mg contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Known or suspected pregnancy. There is no indication for estradiol tablets in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens a...",
  "warnings_and_cautions": "",
  "warnings": "WARNINGS See BOXED WARNINGS . 1. Cardiovascular disorders Estrogen and estrogen/progestin therapy has been associated with an increased risk of cardiovascular events such as myocardial infarction and stroke, as well as venous thrombosis and pulmonary embolism (venous thromboembolism or VTE). Should any of these occur or be suspected estrogens should be discontinued immediately. Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. a. Coronary heart disease and stroke In the Women\u2019s Health Initiative (WHI) study, an increase in the number of myocardial infarctions and strokes has been observed in women receiving CE compared to placebo. These observations are preliminary, and the study is continuing . (See CLINICAL PHARMACOLOGY, Clinical Studies .) In the CE/MPA substudy of WHI, an increased risk of coronary heart disease (CHD) events (defined as nonfatal myocardial infarction and CHD death) was observed in women receiving CE/MPA compared to women receivi...",
  "adverse_reactions": "ADVERSE REACTIONS See BOXED WARNINGS , WARNINGS , and PRECAUTIONS . The following additional adverse reactions have been reported with estrogen and/or progestin therapy. 1. Genitourinary system Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting, dysmenorrhea Increase in size of uterine leiomyomata Vaginitis, including vaginal candidiasis Change in amount of cervical secretion Changes in cervical ectropion Ovarian cancer; endometrial hyperplasia; endometrial cancer 2. Breasts Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer 3. Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure 4. Gastrointestinal Nausea, vomiting Abdominal cramps, bloating Cholestatic jaundice Increased incidence of gallbladder disease Pancreatitis Enlargement of hepatic hemangiomas 5. Skin Chloasma or melasma that may persist when drug is discontinued Erythema multiforme Erythema nodosum Hemorrhagic eruption Loss of scalp hair Hirsutism Pruritus, rash 6. Eyes Retinal vascular thrombosis Steepening of cor...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "",
  "information_for_patients": "B. Patient Information Physicians are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe estradiol tablets.",
  "spl_medguide": "",
  "clinical_studies": "Clinical Studies Osteoporosis Most prospective studies of efficacy for this indication have been carried out in white menopausal women, without stratification by other risk factors, and tend to show a universally salutary effect on bone. The results of a two-year, randomized, placebo-controlled, double-blind, dose-ranging study have shown that treatment with 0.5 mg estradiol daily for 23 days (of a 28 day cycle) prevents vertebral bone mass loss in postmenopausal women. When estrogen therapy is discontinued, bone mass declines at a rate comparable to the immediate postmenopausal period. There is no evidence that estrogen replacement therapy restores bone mass to premenopausal levels. Women\u2019s Health Initiative Studies The Women\u2019s Health Initiative (WHI) enrolled a total of 27,000 predominantly healthy postmenopausal women to assess the risks and benefits of either the use of oral 0.625 mg conjugated estrogens (CE) per day alone or the use of oral 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate (MPA) per day compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of coronary heart disease (CHD) (nonfatal myocardi...",
  "brand_name": "Estradiol",
  "manufacturer": "PharmPak, Inc.",
  "application_number": "ANDA040197",
  "pharm_class_epc": [
   "Estrogen [EPC]"
  ],
  "route": [
   "ORAL"
  ],
  "effective_time": "20250116",
  "set_id": "20b50139-4e13-4f0c-aaf5-ecb83911d9e6",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 73409,
  "serious": 28819,
  "death": 1195,
  "hospitalization": 9515,
  "primary_suspect": 73236,
  "top_reactions": [
   [
    "Drug Ineffective",
    7091
   ],
   [
    "Product Adhesion Issue",
    5758
   ],
   [
    "Off Label Use",
    5744
   ],
   [
    "Headache",
    4532
   ],
   [
    "Fatigue",
    4046
   ],
   [
    "Nausea",
    4005
   ],
   [
    "Pain",
    2965
   ],
   [
    "Hot Flush",
    2873
   ],
   [
    "Diarrhoea",
    2696
   ],
   [
    "Arthralgia",
    2492
   ],
   [
    "Dizziness",
    2453
   ],
   [
    "Wrong Technique In Product Usage Process",
    2418
   ],
   [
    "Rash",
    2249
   ],
   [
    "Pruritus",
    2241
   ],
   [
    "No Adverse Event",
    2157
   ]
  ],
  "by_year": {
   "2019": 7847,
   "2020": 6737,
   "2021": 5584,
   "2022": 5197,
   "2023": 5526,
   "2024": 5714,
   "2025": 7628,
   "2026": 4714
  },
  "by_year_primary": {
   "2019": 7842,
   "2020": 6734,
   "2021": 5553,
   "2022": 5153,
   "2023": 5489,
   "2024": 5690,
   "2025": 7616,
   "2026": 4698
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class II",
   "date": "20260512",
   "reason": "Defective Container; packets were found to be either empty or partially full.",
   "firm": "ANI Pharmaceuticals, Inc.",
   "status": "Ongoing"
  },
  {
   "class": "Class III",
   "date": "20240516",
   "reason": "Failed Impurities/Degradation Specifications.",
   "firm": "Zydus Pharmaceuticals (USA) Inc",
   "status": "Ongoing"
  },
  {
   "class": "Class III",
   "date": "20240516",
   "reason": "Failed Impurities/Degradation Specifications.",
   "firm": "Zydus Pharmaceuticals (USA) Inc",
   "status": "Ongoing"
  },
  {
   "class": "Class III",
   "date": "20230221",
   "reason": "Failed Content Uniformity Specifications: The Spray Content Uniformity (SCU) requirement for Standard Deviation did not meet the requirement at the 18-month stability time point.",
   "firm": "Padagis US LLC",
   "status": "Ongoing"
  },
  {
   "class": "Class II",
   "date": "20220126",
   "reason": "CGMP Deviations: Products were exposed to temperatures outside of the products labeled storage conditions.",
   "firm": "CARDINAL HEALTHCARE",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20210416",
   "reason": "Defective Delivery System: Out of specification for release rate testing and shear, an attribute related to the adhesive properties of the transdermal patches. As a result, patients could experience patches that do not stick well to the ski",
   "firm": "Noven Pharmaceuticals Inc",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20210416",
   "reason": "Defective Delivery System: Out of specification for release rate testing and shear, an attribute related to the adhesive properties of the transdermal patches. As a result, patients could experience patches that do not stick well to the ski",
   "firm": "Noven Pharmaceuticals Inc",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20210315",
   "reason": "CGMP Deviations: Intermittent exposure to temperature excursion during storage.",
   "firm": "Cardinal Health Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20191022",
   "reason": "Defective Delivery System: complaints for difficulty in pushing the plunger of the applicator.",
   "firm": "Glenmark Pharmaceuticals Inc., USA",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20190603",
   "reason": "Defective Delivery System: Estradiol Vaginal Inserts USP plunger is not functioning properly.",
   "firm": "Glenmark Pharmaceuticals Inc., USA",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20181226",
   "reason": "Defective Delivery System: Customer complaints of malfunctioning plunger of the applicator",
   "firm": "Glenmark Pharmaceuticals Inc., USA",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20180907",
   "reason": "Defective Delivery System: out of specification results for shear, an attribute related to the adhesive properties of the transdermal patches.",
   "firm": "Noven Pharmaceuticals, Inc.",
   "status": "Terminated"
  }
 ],
 "recall_total": 21,
 "drugsfda": {
  "applications": 32,
  "nda": 7,
  "anda": 25,
  "first_approval": "19790228",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 53,
  "labeling_recent": 13,
  "sponsors": [
   "ABBVIE",
   "AM REGENT",
   "AMNEAL",
   "AUROBINDO PHARMA",
   "BRISTOL MYERS SQUIBB",
   "DR REDDYS",
   "DURAMED PHARMS BARR",
   "ENCUBE"
  ],
  "unapproved": false,
  "first_approval_fmt": "02/28/1979"
 },
 "trials": {
  "total": 2017,
  "completed": 1142,
  "terminated": 244,
  "with_results": 489,
  "industry": 926,
  "phase3": 358,
  "results_share": 0.42819614711033277,
  "terminated_share": 0.12097174020823004
 },
 "pubmed": {
  "rct": 1090,
  "meta": 48,
  "recent_rct": 91,
  "cochrane": [
   {
    "pmid": "33251587",
    "title": "Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women",
    "year": "2020"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 140238.56,
  "records": 3849,
  "by_name": [
   [
    "Estrogel",
    73588.4
   ],
   [
    "Femring",
    65659.58
   ],
   [
    "Estring",
    990.58
   ]
  ],
  "names_checked": [
   "estradiol",
   "Yuvafem",
   "Dotti",
   "Estring",
   "Imvexxy",
   "Lyllana",
   "Climara",
   "Femring",
   "Vagifem",
   "Estrace",
   "Estrogel",
   "Depo-estradiol",
   "Minivelle",
   "Divigel",
   "Evamist",
   "Menostar",
   "Elestrin",
   "Delestrogen",
   "Alora",
   "Vivelle"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 5150722,
  "beneficiaries": 1950923,
  "spend": 401309836.79999995,
  "by_brand": [
   {
    "brand": "Estradiol",
    "claims": 4055858,
    "per_claim": 53.788441686,
    "is_generic": true
   },
   {
    "brand": "Estradiol (Twice Weekly)",
    "claims": 319673,
    "per_claim": 95.823513434,
    "is_generic": false
   },
   {
    "brand": "Estradiol (Once Weekly)",
    "claims": 212657,
    "per_claim": 86.467562507,
    "is_generic": false
   },
   {
    "brand": "Yuvafem",
    "claims": 203105,
    "per_claim": 149.57359819,
    "is_generic": false
   },
   {
    "brand": "Dotti",
    "claims": 122816,
    "per_claim": 108.4347037,
    "is_generic": false
   },
   {
    "brand": "Estring",
    "claims": 90750,
    "per_claim": 542.01820298,
    "is_generic": false
   },
   {
    "brand": "Imvexxy",
    "claims": 34317,
    "per_claim": 398.37804936,
    "is_generic": false
   },
   {
    "brand": "Lyllana",
    "claims": 24542,
    "per_claim": 112.85631244,
    "is_generic": false
   },
   {
    "brand": "Climara",
    "claims": 22120,
    "per_claim": 138.8360547,
    "is_generic": false
   },
   {
    "brand": "Estradiol Valerate",
    "claims": 14281,
    "per_claim": 129.86319235,
    "is_generic": true
   },
   {
    "brand": "Vivelle-Dot",
    "claims": 10989,
    "per_claim": 292.46102011,
    "is_generic": false
   },
   {
    "brand": "Femring",
    "claims": 9145,
    "per_claim": 763.48551121,
    "is_generic": false
   },
   {
    "brand": "Vagifem",
    "claims": 7733,
    "per_claim": 397.36811587,
    "is_generic": false
   },
   {
    "brand": "Estrace",
    "claims": 6218,
    "per_claim": 315.2047459,
    "is_generic": false
   },
   {
    "brand": "Estrogel",
    "claims": 3339,
    "per_claim": 222.51567236,
    "is_generic": false
   },
   {
    "brand": "Depo-Estradiol",
    "claims": 3076,
    "per_claim": 217.84857932,
    "is_generic": false
   },
   {
    "brand": "Minivelle",
    "claims": 2918,
    "per_claim": 437.32357094,
    "is_generic": false
   },
   {
    "brand": "Divigel",
    "claims": 2356,
    "per_claim": 264.26404499,
    "is_generic": false
   },
   {
    "brand": "Evamist",
    "claims": 1700,
    "per_claim": 221.43227647,
    "is_generic": false
   },
   {
    "brand": "Menostar",
    "claims": 1679,
    "per_claim": 360.54353186,
    "is_generic": false
   },
   {
    "brand": "Elestrin",
    "claims": 975,
    "per_claim": 287.63888205,
    "is_generic": false
   },
   {
    "brand": "Delestrogen",
    "claims": 475,
    "per_claim": 162.89717895,
    "is_generic": false
   }
  ],
  "per_claim": 77.91331716213764
 },
 "mdl": [],
 "dsc": [],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": false,
  "status": "ApplicationRejected",
  "name": "estradiol",
  "matched": "estradiol",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 18004,
  "fills": 5150722,
  "per_million": 3495.4322908516515,
  "ratio": 1.2623675406412564,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 63,
   "letter": "C",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "3,495 FDA reports naming it as the suspect drug per million Medicare fills, 1.3x the median drug on this site (-2)",
    "Death share in reports is near or below the FAERS average (0.2x)",
    "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 75,
   "letter": "B",
   "why": [
    "1090 randomized trials and 48 systematic reviews/meta-analyses indexed in PubMed",
    "1 independent Cochrane review(s) exist",
    "Only 43% of completed registered trials posted results (-8)",
    "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 85,
   "letter": "B",
   "why": [
    "Recalls since 2016: 0 Class I, 16 Class II, 4 Class III across 25 generic makers (-7)",
    "13 label changes approved since 2021: the safety story is still moving (-8)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 85,
   "letter": "B",
   "why": [
    "Pharma paid doctors $140,239 tied to this drug last year (-15)",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 100,
   "letter": "A",
   "why": [
    "Generic versions approved (25 applications)",
    "7 same-class alternatives exist"
   ],
   "weight": 0.1
  }
 },
 "total": 76,
 "grade": "B",
 "questions": [
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are product adhesion issue, headache. How would we recognize and handle those?",
  "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?",
  "Why this one over chlorotrianisene, estetrol, estriol? 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.)"
 ]
}