Estrace
Estradiol · Cream · Vaginal
Uses
(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
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
(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
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 the WHI estrogen-alone substudy, the risk of VTE (DVT and PE) was increased for women receiving daily CE (0.625 mg)-alone compared to women receiving placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years 5 [see CLINICAL STUDIES ]. Should a VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was observed during the first year and persisted 6 [see CLINICAL STUDIES ]. Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. 2. Malignant N eoplasms a. Endometrial C ancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than one year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for five to ten years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued.
Precautions
PRECAUTIONS A. General 1 . Addition of a P rogestin W hen a W oman H as N ot H ad a H ysterectomy Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include a possible increased risk of breast cancer. 2. Elevated B lood P ressure In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen. 3. Hypertriglyceridemia In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis and other complications. Consider discontinuation of treatment if pancreatitis occurs. 4. Hepatic Impair ment and /or P ast H istory of C holestatic J aundice Estrogens may be poorly metabolized in patients with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised and in the case of recurrence, medication should be discontinued. 5. Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T 4 and T 3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range. 6. Fluid R etention Estrogens may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as a cardiac or renal dysfunction, warrant careful observation when estrogen-alone is prescribed. 7. Hypocalcemia Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur . 8. Exacerbation of E ndometriosis A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen alone therapy. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered. 9 . Exacerbation of O ther C onditions Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions. B. P atient I nformation Physicians are advised to discuss the PATIENT INFORMATION leaflet with women for whom they prescribe ESTRACE (estradiol vaginal cream USP 0.01%). C. Laboratory Tests Serum FSH and estradiol levels have not been shown to be useful in the management of moderate to severe symptoms of vulvar and vaginal atrophy. D. D rug- L aboratory T est I nteractions Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone levels, as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay. T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Women on thyroid replacement therapy may require higher dose of thyroid hormone. Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma high-density lipoprotein (HDL) and HDL 2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglycerides levels. Impaired glucose tolerance. E. C arcinogenesis , M utagenesis , and Impairment of Fertility Long-term continuous administration of estrogen, with and without progestin, in women with and without a uterus, has shown an increased risk of endometrial cancer, breast cancer, and ovarian cancer. (See BOXED WARNINGS , WARNINGS and PRECAUTIONS .) Long term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. F. P regnancy ESTRACE should not be used during pregnancy [see CONTRAINDICATIONS ]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy. G. N ursing Mothers ESTRACE should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the milk of women receiving estrogen therapy.
Side effects
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.
Pregnancy
F. P regnancy ESTRACE should not be used during pregnancy [see CONTRAINDICATIONS ]. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.
Pediatric use
H. P ediatric U se ESTRACE Vaginal Cream is not indicated in children. Clinical studies have not been conducted in the pediatric population.
Geriatric use
I. Geriatric Use There have not been sufficient numbers of geriatric patients involved in studies utilizing ESTRACE to determine whether those over 65 years of age differ from younger subjects in their response to ESTRACE. The Women’s Health Initiative Study In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age [see CLINICAL STUDIES and WARNINGS ] . In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age [see CLINICAL STUDIES and WARNINGS ]. The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo [see CLINICAL STUDIES and WARNINGS ]. Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 10 [see CLINICAL STUDIES and WARNINGS ].
Overdosage
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.
Description
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.
How supplied
(estradiol vaginal cream USP 0.01%). N DC 0430-3754-14: Tube containing 1 ½ 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.
Patient information
B. P atient I nformation Physicians are advised to discuss the PATIENT INFORMATION leaflet with women for whom they prescribe ESTRACE (estradiol vaginal cream USP 0.01%). PATIENT INFORMATION EST RA C E ® C R E A M (es-trays) (estradiol vaginal cream USP 0.01%) Read this Patient Information before you start using ESTRACE Vaginal Cream and each time you refill. There may be new information. This information does not take the place of talking with your healthcare provider about your menopausal symptoms or your treatment. W h at is t h e m ost i m p o r t a n t i n f o r m a t ion I s h o u ld kn o w a b o u t E S T RACE Vagi n al C re a m ( an e s tr o g e n h o r m o ne ) ? Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Report any unusual vaginal bleeding right away while you are using ESTRACE Vaginal Cream. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Have your healthcare provider check any unusual vaginal bleeding to find out the cause. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia (decline in brain function). Using estrogen-alone may increase your chances of getting strokes or blood clots. Using estrogen-alone may increase your chance of getting dementia, based on a study of women - 65 years of age or older. Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes or dementia. Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older. Talk regularly with your healthcare provider about whether you still need treatment with ESTRACE Vaginal Cream. W h at is EST RACE V a gi n al C re a m ? ESTRACE Vaginal Cream is a prescription medicine that contains estradiol (an estrogen hormone). W h at is EST RACE V a gi n al C re a m u s e d f o r? EST RACE Vagi n al C re am is u s e d a f te r me n o p a u se t o: T re at m o d e r a t e t o s e v e r e m e n o p a u sal c h a n g e s in a n d a r o u n d t h e vagi n a. Talk regularly with your healthcare provider about whether you still need treatment with ESTRACE. W h o s h o u l d n ot u se E S T RACE Vagi n al C re a m ? Do not start using ESTRACE Vaginal Cream if you: have unu s u a l vagi n al b l ee d i ng. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Have your healthcare provider check any unusual bleeding to find out the cause. c u rre n t ly h ave or h ave h ad cert ain c a n cers . Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use ESTRACE Vaginal Cream. c u rre n t ly h ave or h ave h ad b lo o d c lo t s . had a stroke or heart attack. a r e all er g i c t o EST RACE Vagi n al C re a m or a n y of i t s i n g re d i e n t s. See the list of ingredients in ESTRACE Vaginal Cream at the end of this leaflet. c u rre n t ly h ave or h ave h ad liv e r p r o b l e m s. have b ee n d iag n os e d wi t h a b l ee d i n g d iso r d e r. th i n k you m ay b e p re g n a n t. Before you use ESTRACE Vaginal Cream, tell your healthcare provider about all of your medical conditions, including if you: h ave unu s u al va g i n al b l ee d i ng. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. have any other medical conditions. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), diabetes, epilepsy (seizures), migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. a r e goi n g t o h ave s u r g er y or w ill b e on be d re s t . Your healthcare provider will let you know if you need to stop using ESTRACE Vaginal Cream. are breastfeeding. The hormone in ESTRACE Vaginal Cream can pass into your breast milk. Tell your healthcare provider about the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how ESTRACE works. ESTRACE may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. How s h o u ld I u se E S T RACE Vagi n al C re a m ? ESTRACE Vaginal Cream is a cream that you place in your vagina with the applicator provided with the cream. Take the dose recommended by your healthcare provider and talk to them about how well that dose is working for you. Use estrogens at the lowest dose possible for your treatment only as long as needed. Talk regularly (for example, every 3 to 6 months) with your healthcare provider about the dose you are using and whether you still need treatment with ESTRACE Vaginal Cream. Figure A Step 1 Wash and dry your hands well. Step 2. Remove the cap from the ESTRACE Vaginal Cream tube. (There is no seal on tube). Step 3. Hold the applicator as shown. Do not separate the plunger from applicator (Figure B). Figure B Step 4. Screw threaded end of applicator onto the open nozzle of the ESTRACE Vaginal Cream tube until secure. Do not attach the plunger end of the applicator onto the open ESTRACE Vaginal Cream tube (see Figure C ). Figure C Step 5. Position upright to view the calibrated gram amounts. Step 6. Gently squeeze tube from the bottom to push the prescribed amount of ESTRACE Vaginal Cream into the applicator. As ESTRACE Vaginal Cream is squeezed out, the plunger will rise to indicate the amount of grams (see Figure D). Figure D *This Figure shows a 2 g dose for illustrative purposes only. Your prescribed dosage may vary. Step 7.
Label text from the FDA structured product label by Allergan, Inc. (revised May 29, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Estradiol in 2 products
Estrace NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-2321 | Estradiol .1 mg/g Cream | A-S Medication Solutions | ANDA |
| 0430-3754 | Estradiol .1 mg/g Cream | Allergan, Inc. | ANDA |
Frequently asked questions
What is Estrace used for?
(estradiol vaginal cream USP 0.01%) is indicated in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
What are the side effects of Estrace?
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… See the full label for the complete list.
Who makes Estrace?
Estrace is listed by 2 labelers in the FDA NDC directory, including A-S Medication Solutions, Allergan, Inc..