Estradiol 10 ug Insert, 8-count
Other active recalls for Estradiol (different manufacturers) — 4 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Radioactive Diagnostic Agent class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Estradiol is a form of estrogen — the main female sex hormone. When estrogen levels fall after menopause (or due to other conditions like ovarian failure), you can get symptoms lik...
- What exactly is estradiol and why has my doctor prescribed it?
- Apply the patch to a clean, dry area of skin — usually the lower abdomen. Never put it on your breasts. Press it firmly in place and leave it on for the full wear period — once a w...
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Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Estradiol — tap one for details:
Estradiol may be associated with lower levels of 5 nutrients — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII B1QE5P712K
Hypromellose 2208 is a plant-derived thickening agent that dissolves in water. It's used as a binder to help hold tablet ingredients together and as a coating on pills to control how quickly the medicine releases in your body.
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UNII 36SFW2JZ0W
Hypromellose 2910 is a plant-based thickening agent derived from cellulose. In medicines, it forms a protective coating on tablets or capsules and controls how quickly the drug dissolves and releases into your body.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 30IQX730WE
Polyethylene glycol 6000 is a synthetic polymer made from ethylene glycol units. It acts as a binder, filler, and solubilizer in medicines to help hold ingredients together, add bulk, and improve how well active drugs dissolve and absorb.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $7.56 | $60.49 / 8 insert |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Estradiol 10 ug 00093-3223-08 | Teva | 8 inserts | $5.645 | AB | Availability likely | — |
| Estradiol Vaginal Inserts 10 ug 59651-0439-08 | Aurobindo | 1 tablet | $5.645 | AB | Availability likely | — |
| Yuvafem 10 ug 65162-0226-21 | Amneal | 8 tablets | $5.645 | AB | Availability likely | — |
| Estradiol Vaginal Inserts 10 ug 68462-0711-71 | Glenmark | 1 tablet | $5.645 | AB | Availability likely | — |
| Estradiol Vaginal Inserts 10 ug 72603-0874-08 | NorthStar | 1 tablet | $5.645 | AB | Availability likely | — |
| Vagifem 10 ug 00169-5176-03 | Novo | 8 inserts | $20.324 | AB | Availability likely | — |
| Yuvafem 10 ug 42291-0962-08 | AvKARE | 8 tablets | — | AB | FDA listed | — |
| Estradiol 10 ug 53746-0226-21 | Amneal | 8 inserts | — | AB | FDA listed | — |
| Estradiol 10 ugthis 63629-8803-01 | Bryant | 8 inserts | — | AB | FDA listed | — |
| Estradiol 10 ug 63629-8804-01 | Bryant | 18 inserts | — | AB | FDA listed | — |
| Imvexxy 10 ug 68308-0748-00 | Mayne | 2 inserts | — | AB | Discontinued | — |
| Imvexxy 10 ug 50261-0110-02 | Mayne | 2 inserts | — | AB | Discontinued | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63629-8803-01 You're viewing this | 8 BLISTER PACK in 1 CARTON (63629-8803-1) / 1 APPLICATOR in 1 BLISTER PACK / 1 INSERT in 1 APPLICATOR | 2021-09-10 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER 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 progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions ( 5.3 )] .
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 Warnings and Precautions ( 5.2 ), and Clinical Studies ( 14.2 )] . 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 and 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 Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.3 )] . Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.2 , 5.4 ), and Clinical Studies ( 14.2 , 14.3 )] . Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI.
Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens 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 The WHI estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), DVT, 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 Warnings and Precautions ( 5.2 ), and Clinical Studies ( 14.2 )] .
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 and 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 Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.5 ), and Clinical Studies ( 14.3 )] . Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions ( 5.2 , 5.4 ), and Clinical Studies ( 14.2 , 14.3 )] .
Breast Cancer The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions ( 5.3 ), and Clinical Studies ( 14.2 )] . Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus pro…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Estradiol vaginal inserts are an estrogen indicated for the treatment of atrophic vaginitis due to menopause ( 1.1 )
1.1 Treatment of Atrophic Vaginitis due to Menopause
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women with a history of endometriosis may need a progestogen [see Warnings and Precautions ( 5.3 , 5.15 )] .
Use estrogen-alone, or in combination with a progestogen, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. Administer estradiol vaginal inserts intravaginally: 1 insert daily for 2 weeks, followed by 1 insert twice weekly (for example, Tuesday and Friday) ( 2.1 )
2.1Treatment of Atrophic Vaginitis due to Menopause Administer estradiol vaginal inserts intravaginally using the supplied applicator: 1 insert daily for 2 weeks, followed by 1 insert twice weekly (for example, Tuesday and Friday).
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Estradiol vaginal inserts, USP are white to off-white, round, film-coated, unscored, biconvex inserts containing 10 mcg of estradiol. Each vaginal insert is 6 mm in diameter and is administered in a disposable applicator. Vaginal Insert: One 10 mcg vaginal insert contains 10.3 mcg of estradiol hemihydrate equivalent to 10 mcg of estradiol ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Estradiol vaginal inserts is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.3 )]. Breast cancer or a history of breast cancer [ see Warnings and Precautions ( 5.3 )]. Estrogen-dependent neoplasia [ see Warnings and Precautions ( 5.3 )].
Active DVT, PE, or history of these conditions [see Warnings and Precautions ( 5.2 )]. Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions [see Warnings and Precautions ( 5.2 )]. Known anaphylactic reaction, or angioedema, or hypersensitivity to estradiol vaginal inserts [see Warnings and Precautions ( 5.16 )].
Hepatic impairment or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Undiagnosed abnormal genital bleeding ( 4 , 5.3 ) Breast cancer or a history of breast cancer ( 4 , 5.3 ) Estrogen-dependent neoplasia ( 4 , 5.3 ) Active DVT, PE, or history of these conditions ( 4 , 5.2 ) Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions ( 4 , 5.2 ) Known anaphylactic reaction, angioedema, or hypersensitivity to estradiol vaginal inserts ( 4 , 5.16 ) Hepatic impairment or disease ( 4 , 5.11 ) Protein C, protein S, or antithrombin deficient, or other known thrombophilic disorders ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Estrogens increase the risk of gallbladder disease ( 5.5 ) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.6 , 5.7 , 5.10 , 5.11 ) The estradiol vaginal inserts applicator may cause vaginal abrasion ( 5.18 ) Monitor thyroid function in women on thyroid replacement therapy ( 5.12 , 5.19 )
5.1Risks from Systemic Absorption Estradiol vaginal inserts are intended only for vaginal administration. Systemic absorption occurs with the use of estradiol vaginal inserts. The warnings, precautions, and adverse reactions associated with the use of systemic estrogen-alone therapy should be taken into account.
5.2Cardiovascular Disorders Increased risks of stroke and DVT are reported with estrogen-alone therapy. Increased risks of PE, DVT, stroke, and MI are reported with estrogen plus progestin therapy. Immediately discontinue estrogen with or without progestogen therapy if any of these occur or are suspected.
Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus). Stroke The WHI estrogen-alone substudy reported a statistically significant increased risk of stroke 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, respectively).
The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies ( 14.2 )] . Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected. 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).
1 The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke 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, respectively) [see Clinical Studies ( 14.2 )] . The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen with or without progestogen therapy if a stroke occurs or is suspected.
Coronary Heart Disease The WHI estrogen-alone substudy reported no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies ( 14.2 )] . Subgroup analysis of women 50 to 59 years of age, who were less than 10 years since menopause, suggests a reduction (not statistically significant) of CHD events in those women receiving daily CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-years).
1 The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of CHD events 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). 1 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 ( 14.2 )] . In postmenopausal women with documented heart disease (n=2,763), average 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 CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo gr…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions ( 5.2 )] Malignant Neoplasms [see Boxed Warning , Warnings and Precautions ( 5.3 )] The most common adverse reactions (incidence ≥5 percent) with estradiol vaginal inserts are: back pain, vulvovaginal pruritus, vulvovaginal mycotic infection and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction 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. In a 12-month randomized, double-blind, parallel group, placebo-controlled study, a total of 309 postmenopausal women were randomized to receive either placebo or estradiol 10 mcg vaginal inserts. Adverse reactions with an incidence of ≥5 percent in the estradiol 10 mcg group and greater than those reported in the placebo group are listed in Table 1.
Table 1: Treatment-Emergent Adverse Reactions Reported at a Frequency of ≥ 5 Percent in Women Receiving Estradiol 10 mcg Body System Adverse Reaction Treatment Number (%) of Women Placebo N = 103 n (%) Estradiol N = 205 n (%) Body As A Whole Back Pain 2 (2) 14 (7) Digestive System Diarrhea 0 11 (5) Urogenital System Vulvovaginal Mycotic Infection 3 (3) 17 (8) Vulvovaginal Pruritus 2 (2) 16 (8) N = Total number of women in study. n = Number of women who experienced adverse reactions.
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of estradiol 10 mcg. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders Diarrhea General disorders and administration site conditions Drug ineffective Immune system disorders Hypersensitivity Investigations Blood estrogen increased Weight increased Metabolism and nutrition disorders Fluid retention Neoplasms benign and malignant Breast cancer Endometrial cancer Psychiatric disorders Depression Insomnia Central Nervous System Aggravated migraine Reproductive system and breast disorders Endometrial hyperplasia Vulvovaginal burning sensation Vulvovaginal pain Genital pruritus Vulvovaginal rash Vulvovaginal swelling Vaginismus Vaginal ulceration Skin and subcutaneous tissue disorders Rash Rash erythematous Rash pruritic Urticaria Vascular disorders Deep vein thrombosis
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St.
John’s wort ( Hypericum perforatum ) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Estradiol vaginal inserts are not indicated for use in pregnancy. There are no data with the use of estradiol vaginal inserts in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2Lactation Risk Summary Estrogens are present in human milk and can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for estradiol vaginal inserts and any potential adverse effects on the breastfed child from estradiol vaginal inserts or from the underlying maternal condition.
8.4Pediatric Use Estradiol vaginal inserts are not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol vaginal inserts to determine whether those over 65 years of age differ from younger subjects in their response to estradiol vaginal inserts. The Women’s Health Initiative Studies 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 ( 14.2 )] . 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 ( 14.2 )] .
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 Warnings and Precautions ( 5.4 ), and Clinical Studies ( 14.3 )] . 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 8 [see Warnings and Precautions ( 5.4 ), and Clinical Studies ( 14.3 )] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Estradiol vaginal inserts are not indicated for use in pregnancy. There are no data with the use of estradiol vaginal inserts in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Estradiol vaginal inserts are not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
🧓 Geriatric Use ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol vaginal inserts to determine whether those over 65 years of age differ from younger subjects in their response to estradiol vaginal inserts. The Women’s Health Initiative Studies 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 ( 14.2 )] . 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 ( 14.2 )] .
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 Warnings and Precautions ( 5.4 ), and Clinical Studies ( 14.3 )] . 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 8 [see Warnings and Precautions ( 5.4 ), and Clinical Studies ( 14.3 )] .
🆘 Overdosage ▾
10 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 estradiol therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH, through a negative feedback mechanism.
Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
12.2Pharmacodynamics Generally, a serum concentration does not predict an individual woman’s therapeutic response to estradiol vaginal inserts nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.
12.3Pharmacokinetics Absorption Estrogen drug products are well absorbed through the skin, mucous membranes, and the gastrointestinal tract. The vaginal delivery of estrogens circumvents first-pass metabolism. In a single-center, randomized, open-label, multiple-dose study conducted in 29 patients, estradiol vaginal inserts 10 mcg demonstrated a mean estradiol (E2) C ave at Day 83 of 5.5 pg/mL after 12 weeks of treatment (see Table 2).
Table 2: Arithmetic Means of Estradiol (E2), Estrone (E1), and Estrone Sulfate (E1S) PK Parameters Following Multiple Doses a of Estradiol 10 mcg Uncorrected for baseline, N=29 E2 E1 E1S AUC 0-24 C ave (0-24) %CV b AUC 0-24 C ave (0-24) %CV b AUC 0-24 C ave (0-24) %CV b (h.pg/mL) (pg/mL) (h.pg/mL) (pg/mL) (h.pg/mL) (pg/mL) Day 1 242.08 10.09 33.02 485.21 20.22 44.86 5158.32 214.93
53.57Day 176.49 7.35 43.69 496.14 20.67 30.88 6323.41 263.48 50.07 14 Day 132.04 5.50 59.69 411.08 17.13 39.58 3804.65 158.53 49.76 83 a Patients received vaginal inserts as a once daily intravaginal treatment for the first 2 weeks and a twice weekly intravaginal maintenance for the following 10 weeks. b CV: Coefficient of Variance for both AUC 0-24 and C ave(0-24) Distribution The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs.
Estrogens circulate in the blood largely bound to SHBG and albumin. Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions.
These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption.
In postmenopausal women, a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. Excretion Estradiol, estrone, and estriol are excreted in the uri…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH, through a negative feedback mechanism.
Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Estradiol vaginal inserts USP, 10 mcg, are white to off-white, round, film-coated, unscored, biconvex inserts, debossed with " TV " on one side and " T5 " on the other side. Each insert is contained in a disposable, single-use applicator, packaged in a blister pack. Cartons contain 8 applicators with inset inserts. Estradiol vaginal inserts USP, 10 mcg: 8 applicators: NDC: 63629-8803-1 Keep out of reach of children
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Do not refrigerate. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504
📋 Description ▾
11 DESCRIPTION Estradiol vaginal inserts USP, 10 mcg are white to off-white, round, film-coated, unscored, biconvex inserts containing 10.3 mcg of estradiol hemihydrate, USP equivalent to 10 mcg of estradiol. Each 10 mcg estradiol vaginal insert contains the following excipients: corn starch, hypromellose, lactose monohydrate, magnesium stearate, and polyethylene glycol. Each estradiol vaginal insert is 6 mm in diameter and is placed in a disposable applicator.
Each insert-filled applicator is packaged separately in a blister pack. Estradiol vaginal inserts are used intravaginally. When the insert comes in contact with the vaginal mucosa, estradiol is released into the vagina.
Estradiol hemihydrate, USP is white to practically white crystals or powder and chemically described as estra1,3,5 (10)-triene-3,17β-diol, hydrate (2:1). The structural formula is: C 18 H 24 O 2 . 1/2 H 2 O M.W.
281.4 (Estradiol hemihydrate, USP) FDA approved dissolution test specifications differ from USP.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions ( 5.3 )] . Possible Serious Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 )] .
Possible Common Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen-alone therapy such as headache, breast pain and tenderness, nausea and vomiting. Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. F 4/2024