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ESTRACE
estradiol · Cream
Overview
Active ingredients
Source: NDC Directory| Ingredient | Strength | RxCUI | Monograph |
|---|---|---|---|
| Estradiol | .1 mg/g | 197657 | View |
Forms, strengths and routes
Source: NDC DirectoryPharmacologic classes are listed in the class section below.
Pharmacologic class
Source: NDC Directory| Class | Type | Browse |
|---|---|---|
| Estradiol Congeners [CS] | CS | All 30 members |
| Estrogen Receptor Agonists [MoA] | MoA | All 45 members |
| Estrogen [EPC] | EPC | All 45 members |
Regulatory status
Source: Drugs@FDANDC Directory| Product | Trade name | Form | Strength | Ingredient | Status | TE | Flags |
|---|---|---|---|---|---|---|---|
| 086069-001 | ESTRACE | CREAM | ESTRADIOL | Prescription | AB | RLD RS |
Therapeutic equivalence
Source: Orange BookWhat this rating means: Therapeutically equivalent — bioequivalence demonstrated by in vivo or in vitro testing
Codes beginning with “A” indicate products the FDA considers therapeutically equivalent. Codes beginning with “B” indicate bioequivalence has not been established. See methodology.
Approval history
Source: Drugs@FDA| Type | No. | Action | Status | Date | Review |
|---|---|---|---|---|---|
| Supplement | 27 | Labeling | Approved | February 15, 2024 | Standard |
| Supplement | 26 | Labeling | Approved | November 30, 2022 | Standard |
| Supplement | 24 | Labeling | Approved | August 15, 2018 | Standard |
| Supplement | 23 | Labeling | Approved | June 21, 2017 | Standard |
| Supplement | 18 | Labeling | Approved | August 17, 2005 | — |
| Supplement | 17 | Manufacturing (CMC) | Approved | March 27, 2001 | — |
| Supplement | 16 | Labeling | Approved | August 11, 2000 | — |
| Supplement | 15 | Manufacturing (CMC) | Approved | August 11, 2000 | — |
| Supplement | 12 | Labeling | Approved | August 3, 1998 | — |
| Supplement | 11 | Manufacturing (CMC) | Approved | September 9, 1997 | — |
| Supplement | 10 | Labeling | Approved | December 31, 1996 | — |
| Supplement | 9 | Manufacturing (CMC) | Approved | January 14, 1994 | — |
| Supplement | 8 | Labeling | Approved | September 23, 1992 | — |
| Supplement | 5 | Labeling | Approved | March 11, 1992 | — |
| Supplement | 7 | Labeling | Approved | June 7, 1991 | — |
| Supplement | 3 | Manufacturing (CMC) | Approved | October 16, 1987 | — |
| Supplement | 2 | Manufacturing (CMC) | Approved | July 17, 1986 | — |
| Original application | 1 | Approved | January 31, 1984 | — |
Prescribing information
Source: openFDA Drug LabelingReproduced verbatim from the Structured Product Labeling submitted to the FDA (effective 20240529). This is the manufacturer's labelling text, not a summary and not advice.
Boxed Warning
openFDA Drug LabelingWARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see WARNINGS , Malignant Neoplasms , Endometrial Cancer ]. Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see CLINICAL STUDIES and WARNINGS , Cardiovascular Disorders , and Probable Dementia ]. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo [see CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders ]. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) -alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see CLINICAL STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use ]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see CLINICAL STUDIES and WARNINGS , Cardiovascular Disorders , and Probable Dementia ]. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see CLINICAL STUDIES and WARNINGS , Cardiovascular Disorders ]. The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see CLINICAL STUDIES and WARNINGS , Probable Dementia and PRECAUTIONS , Geriatric Use ]. Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see CLINICAL STUDIES and WARNINGS , Malignant Neoplasms , Breast Cancer ]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Indications and Usage
openFDA Drug LabelingINDICATIONS AND USAGE ESTRACE (estradiol vaginal cream USP 0.01%) is indicated in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
Dosage and Administration
openFDA Drug LabelingDOSAGE AND ADMINISTRATION Use of ESTRACE alone or in combination with a progestin, should be limited to the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should reevaluate periodically as clinically appropriate to determine if treatment is still necessary. For treatment of vulvar and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. For women who have a uterus, adequate diagnostic measures, including directed and random endometrial sampling when indicated, should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal genital bleeding. Usual Dosage: The usual dosage range is 2 to 4 g (marked on the applicator) daily for one or two weeks, then gradually reduced to one half initial dosage for a similar period. A maintenance dosage of 1 g, one to three times a week, may be used after restoration of the vaginal mucosa has been achieved. NOTE: The number of doses per tube will vary with dosage requirements and patient handling.
Contraindications
openFDA Drug LabelingCONTRAINDICATIONS ESTRACE (estradiol vaginal cream USP 0.01%) should not be used in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Known, suspected, or history of cancer of the breast. Known or suspected estrogen-dependent neoplasia. Active DVT, PE or history of these conditions. Active arterial thromboembolic disease (for example, stroke, MI) or a history of these conditions. Known anaphylactic reaction or angioedema to ESTRACE (estradiol vaginal cream USP 0.01%). Known liver dysfunction or disease. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy.
Warnings
openFDA Drug LabelingWARNINGS See BOXED WARNINGS . Systemic absorption may occur with the use of ESTRACE (estradiol vaginal cream USP 0.01%). The warnings, precautions, and adverse reactions associated with oral estrogen treatment should be taken into account. 1. Cardiovascular D isorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke and MI has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately. Risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. a. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted [see CLINICAL STUDIES ]. Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years) 3 . In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years) [see CLINICAL STUDIES ]. The increase in risk was demonstrated after the first year and persisted 3 . Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. b. Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI and CHD death) was reported in women receiving estrogen-alone compared to placebo 4 [see CLINICAL STUDIES ]. Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years) 3 . In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years) 3 . An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see CLINICAL STUDIES ]. In postmenopausal women with documented heart disease (n = 2,763), average age 66.7 years of age, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand, three hundred and twenty one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in HERS, HERS II, and overall. c. Venous Thromboembolism In t …
Adverse Reactions
openFDA Drug LabelingADVERSE REACTIONS See BOXED WARNINGS , WARNINGS and PRECAUTIONS . Systemic absorption may occur with the use of ESTRACE. The warnings, precautions, and adverse reactions associated with oral estrogen treatment should be taken into account. The following adverse reactions have been reported with estrogen and/or progestin therapy. 1. Genitourinary S ystem Abnormal uterine bleeding or spotting; dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in cervical secretion; cystitis-like syndrome; application site reactions of vulvovaginal discomfort including burning and irritation; genital pruritus; ovarian cancer; endometrial hyperplasia; endometrial cancer. 2. Breasts Tenderness, enlargement, pain, nipple discharge, fibrocystic breast changes; breast cancer. 3. Cardiovascular Deep and superficial venous thrombosis; pulmonary embolism; myocardial infarction; stroke; increase in blood pressure. 4. Gastrointestinal Nausea, vomiting; abdominal cramps, bloating; increased incidence of gallbladder disease. 5. Skin Chloasma that may persist when drug is discontinued; loss of scalp hair; hirsutism; rash. 6. Eyes Retinal vascular thrombosis, intolerance to contact lenses. 7. Central N ervous S ystem Headache; migraine; dizziness; mental depression; nervousness; mood disturbances; irritability; dementia. 8. Miscellaneous Increase or decrease in weight; glucose intolerance; edema; arthralgias; leg cramps; changes in libido; urticaria; exacerbation of asthma; increased triglycerides; hypersensitivity.
Description
openFDA Drug LabelingDESCRIPTION Each gram of ESTRACE (estradiol vaginal cream USP 0.01%) contains 0.1 mg estradiol in a nonliquefying base containing purified water, propylene glycol, stearyl alcohol, white ceresin wax, mono- and di-glycerides, hypromellose 2208 (4000 cps), sodium lauryl sulfate, methylparaben, edetate di-sodium and tertiary -butylhydroquinone. Estradiol is chemically described as estra-1,3,5(10)-triene-3, 17(beta)-diol. It has an empirical formula of C 18 H 24 O 2 and molecular weight of 272.37. The structural formula is: The structural formula for ESTRACE (estradiol vaginal cream, USP, 0.01%) contains 0.1 mg estradiol in a nonliquefying base containing purified water, propylene glycol, stearyl alcohol, white ceresin wax, mono- and di-glycerides, hypromellose 2208 (4000 cps), sodium lauryl sulfate, methylparaben, edetate di-sodium and tertiary-butylhydroquinone. Estradiol is chemically described as estra-1,3,5(10)-triene-3, 17(beta)-diol. It has an empirical formula of C18H24O2 and molecular weight of 272.37.
Overdosage
openFDA Drug LabelingOVERDOSAGE Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of ESTRACE therapy together with institution of appropriate symptomatic care.
How Supplied / Storage and Handling
openFDA Drug LabelingHOW SUPPLIED ESTRACE (estradiol vaginal cream USP 0.01%). N DC 0430-3754-14: Tube containing 1 1⁄2 oz (42.5 g) with a calibrated plastic applicator for delivery of 1, 2, 3, or 4 g. Smooth semi solid cream. White or off-white. S t o r e at r o o m t e m p er a t u r e 20° t o 25°C ( 59° t o 77° F ) . P r o t ec t f r o m t e m p er a t u re s in e x c e ss of 40°C ( 104° F ) . Keep ESTRACE Vaginal Cream out of the reach of children.
Adverse event reports
Source: openFDA FAERSAttributed to this product's most-reported active ingredient: ESTRADIOL. Combination products with more than six active ingredients are not attributed, because a report count summed across a long ingredient list measures the list, not the medicine.
Packaging and NDCs
Source: NDC Directory| Package NDC | Product NDC | Labeler | Description | Marketing start |
|---|---|---|---|---|
| 50090-2321-0 | 50090-2321 | A-S Medication Solutions | 1 TUBE in 1 CARTON (50090-2321-0) / 42.5 g in 1 TUBE | March 2, 2016 |
| 0430-3754-14 | 0430-3754 | Allergan, Inc. | 36 CARTON in 1 CASE (0430-3754-14) / 1 TUBE, WITH APPLICATOR in 1 CARTON / 42.5 g in 1 TUBE, WITH APPLICATOR | July 1, 2001 |
| 50090-2321 | 50090-2321 | A-S Medication Solutions | — | July 1, 2001 |
| 0430-3754 | 0430-3754 | Allergan, Inc. | — | July 1, 2001 |
Sources for this page
| Dataset | Agency | Used for |
|---|---|---|
| NDC Directory | FDA | Identity, ingredients, strengths, forms, routes, labelers, packages |
| Drugs@FDA | FDA | Application, sponsor, submissions, review documents, marketing status |
| Orange Book | FDA | Therapeutic equivalence codes, reference drug flags, patents, exclusivity |
| Drug Labeling | FDA / NLM | Prescribing information reproduced above |
| FAERS | FDA | Adverse event report counts |
Generated September 25, 2026 · 11 sections on this page.