Yuvafem Estradiol 10 ug Tablet, 18-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.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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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 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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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.
5 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 | $7.62 | $137.24 / 18 tablet |
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🔁 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 ugthis 42291-0962-18 | AvKARE | 18 tablets | — | AB | FDA listed | — |
| Estradiol 10 ug 53746-0226-21 | Amneal | 8 inserts | — | AB | FDA listed | — |
| Estradiol 10 ug 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 | — |
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 |
|---|---|---|---|
| 42291-0962-08 | 8 APPLICATOR in 1 CARTON (42291-962-08) / 1 TABLET in 1 APPLICATOR (42291-962-11) | 2016-10-19 | Active |
| 42291-0962-18 You're viewing this | 18 APPLICATOR in 1 CARTON (42291-962-18) / 1 TABLET in 1 APPLICATOR (42291-962-11) | 2016-10-19 | Active |
Pack size FAQ
What quantity is in NDC 42291-0962-18?
What is the difference between NDC 42291-0962-18 and NDC 42291-0962-08?
What NDC number is used to bill for this package of Yuvafem Estradiol 10 ug Tablet?
🧭 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
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: 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 and Precautions (5.3) ] .
Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.2, 5.4) and Clinical Studies (14.2, 14.3) ] . 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 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 Warnings and Precautions (5.4) , Use in Specific Populations (8.5) and Clinical Studies (14.3) ] . 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 Warnings and Precautions (5.2, 5.4) and Clinical Studies (14.2, 14.3) ] . 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 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 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 Warnings and Precautions (5.4) , Use in Specific Populations (8.5) and Clinical Studies (14.3) ] . Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.3) and Clinical Studies (14.2) ] .
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. WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA See full prescribing information for complete boxed warning.
Estrogen-Alone Therapy There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens (5.3) Estrogen-alone therapy should not be used for the prevention of…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Yuvafem are an estrogen (estradiol) indicated for the treatment of atrophic vaginitis due to menopause (1.1)
1.1Treatment 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, a progestin should also be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.3, 5.15) ] .
Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. Yuvafem should be administered 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 Yuvafem should be administered intravaginally using the supplied applicator: 1 insert daily for 2 weeks, followed by 1 insert twice weekly (for example, Tuesday and Friday). Generally, women should be started at the 10 mcg dosage strength.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Yuvafem are small, white, round, film-coated, bi-convex vaginal inserts containing 10 mcg of estradiol. Each vaginal insert is 6 mm in diameter and is administered in a disposable applicator. Yuvafem, 10 mcg: One vaginal insert contains 10.3 mcg of estradiol hemihydrate, USP equivalent to 10 mcg of estradiol, USP (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Yuvafem should not be used in women with any of the following conditions: Undiagnosed abnormal genital bleeding Known, suspected, or history of breast cancer Known or suspected estrogen-dependent neoplasia Active DVT, PE, or history of these conditions Active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions Known anaphylactic reaction or angioedema to Yuvafem Known liver impairment or disease Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Known or suspected pregnancy Undiagnosed abnormal genital bleeding (4) Known, suspected, or history of breast cancer (4, 5.3) Known or suspected estrogen-dependent neoplasia (4, 5.3) Active DVT, PE, or history of these conditions (4, 5.2) Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions (4, 5.2) Known anaphylactic reaction or angioedema to Yuvafem Known liver impairment or disease (4, 5.11) Known protein C, protein S, or antithrombin deficient, or other known thrombophilic disorders (4) Known or suspected pregnancy (4, 8.1)
⚠️ 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 Yuvafem applicator may cause vaginal abrasion (5.17) Monitor thyroid function in women on thyroid replacement therapy (5.12, 5.19)
5.1Risks from Systemic Absorption Yuvafem are intended only for vaginal administration. Systemic absorption occurs with the use of Yuvafem. The warnings, precautions and adverse reactions associated with the use of systemic estrogen-alone therapy should be taken into account.
5.2Cardiovascular Disorders 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 (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) should be managed appropriately. 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 1 and persisted [see Clinical Studies (14.2) ] . 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).
1 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 (14.2) ] . The increase in risk was demonstrated after the first year and persisted. 1 Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.
Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.2) ] . Subgroup analysis of women 50 to 59 years of age suggests 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). 1 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).
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 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 d…
🤒 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) ] In prospective, randomized, placebo-controlled, double-blind studies the most common adverse reactions (incidence ≥5 percent) were upper respiratory tract infection, headache, abdominal pain, back pain, genital pruritus, moniliasis, vulvovaginal mycotic infection and diarrhea.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE, Inc. at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 Yuvafem 10 mcg inserts. Adverse reactions with an incident of > 5 percent in the Yuvafem 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 Yuvafem 10 mcg Body System Adverse Reaction Treatment Number (%) of Women Placebo N = 103 n = (%) Yuvafem 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) Vulvavaginal Pruritus 2 (2) 16 (8) N = Total number of women in study. n = Number of women who experienced adverse reactions. In a 12-week, randomized, double-blind, placebo-controlled study, 138 postmenopausal women were randomized to receive either placebo or Yuvafem 10 mcg inserts.
Adverse reactions with an incident of > 5 percent in the Yuvafem 25 mcg group and greater than those reported in the placebo group are listed in Table 2. Table 2: Treatment-Emergent Adverse Reactions Reported at a Frequency of > 5 Percent in Women Receiving Yuvafem 25 mcg Body System Adverse Reaction Treatment Number (%) of Women Placebo N = 47 N (%) Yuvafem N = 91 n (%) Body As A Whole Headache 3 (6) 8 (9) Abdominal Pain 2 (4) 6 (7) Back Pain 3 (6) 6 (7) Respiratory System Upper Respiratory Tract Infection 2 (4) 5 (5) Urogenital System Moniliasis Genital 1 (2) 5 (5) 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 Yuvafem 25 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. Genitourinary System Endometrial cancer, endometrial hyperplasia, vaginal irritation, vaginal pain, vaginismus, vaginal ulceration Breast Breast cancer Cardiovascular Deep vein thrombosis Gastrointestinal Diarrhea Skin Urticaria, erythematous or pruritic rash, genital pruritus Central Nervous System Aggravated migraine, depression, insomnia Miscellaneous Fluid retention, weight increase, drug ineffectiveness, hypersensitivity, blood estrogen increase Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy.
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug-drug interaction studies have been conducted for Yuvafem. Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism (7.1)
7.1Metabolic 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 side effects.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Estrogen administration to nursing women has been shown to decrease the quantity and quality of breast milk (8.3) Geriatric Use: An increased risk of probable dementia in women over 65 years of age was reported in the Women’s Health Initiative Memory ancillary studies of the Women’s Health Initiative (8.5) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 11/2017
8.1Pregnancy Yuvafem should not be used during pregnancy [see Contraindications (4) ] . 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.
8.3Nursing Mothers Yuvafem 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 breast milk of women receiving estrogen therapy. Caution should be exercised when Yuvafem is administered to a nursing woman.
8.4Pediatric Use Yuvafem is not indicated in children. 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 Yuvafem to determine whether those over 65 years of age differ from younger subjects in their response to Yuvafem. 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) ] .
8.6Renal Impairment The effect of renal impairment on the pharmacokinetics of Yuvafem has not been studied.
8.7Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of Yuvafem has not been studied.
🆘 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 Yuvafem 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 Currently, there are no pharmacodynamic data known for Yuvafem.
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, parallel group study conducted in 58 patients, Yuvafem 10 mcg demonstrated a mean estradiol (E2) C ave at Day 83 of 5.5 pg/mL and 11.59 pg/mL, respectively after 12 weeks of treatment (see Table 3).
Table 3: Arithmetic Means of Estradiol (E2), Estron (E1), and Estrone Sulfate (E1S) PK Parameters Following Multiple Doses a of Yuvafem 10 mcg Uncorrected for baseline, N=29 E2 E1 E1S AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b Day 1 242.08 10.09 33.02 485.21 20.22 44.86 5158.32 214.93
53.57Day 14 176.49 7.35 43.69 496.14 20.67 30.88 6323.41 263.48
50.07Day 83 132.04 5.50 59.69 411.08 17.13 39.58 3804.65 158.53 49.76 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) Table 4: Arithmetic Means of Estradiol (E2), Estron (E1), and Estrone Sulfate (E1S) PK Parameters Following Multiple Doses a of Yuvafem 10 mcg Uncorrected for baseline, N=29 E2 E1 E1S AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b AUC 0-24 (h.pg/mL) C ave (0-24) (pg/mL) %CV b Day1 495.27 20.64 25.70 567.07 23.63 28.96 5738.32 239.10
47.72Day 14 466.63 19.44 33.53 662.94 27.62 24.36 7725.90 321.91
43.67Day 83 278.27 11.59 61.83 500.06 20.84 34.99 4110.84 171.29 51.38 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) c N=28 for treatment before Day 14 and N=27 for treatments from Day 14. 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 liv…
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Yuvafem, 10 mcg , are supplied as white to off-white, round biconvex, film-coated unscored inserts debossed with “276” on obverse and “AN” on the reverse. Each Yuvafem, 10 mcg , is contained in a disposable, single-use applicator, packaged in a blister pack. Cartons contain 8 or 18 applicators with inset inserts. Yuvafem, 10 mcg 8 applicators: NDC 42291-962-08 18 applicators: NDC 42291-962-18 Keep out of reach of children
16.2Storage and Handling Store at 20º to 25ºC (68º to 77ºF), excursions permitted to 15º to 30ºC (59º to 86ºF) [See USP Controlled Room Temperature]. Do not refrigerate.
📋 Description ▾
11 DESCRIPTION Yuvafem (estradiol vaginal inserts), 10 mcg, are small, white, film-coated insertts containing 10.3 mcg of estradiol hemihydrate equivalent to 10 mcg of estradiol, USP. Each Yuvafem, 10 mcg contains the following excipients: corn starch, hypromellose, lactose monohydrate and magnesium stearate. The film coating contains hypromellose and polyethylene glycol.
Each Yuvafem 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. Yuvafem are used intravaginally.
When the insert comes in contact with the vaginal mucosa, estradiol, USP is released into the vagina. USP Dissolution Test is pending. Estradiol hemihydrate is a white, almost white or colorless crystalline solid, chemically described as estra-1,3,5 (10)-triene-3,17β-diol.
The chemical formula is C 18 H 24 O 2 • ½ H 2 O with a molecular weight of 281.4. The structural formula is: 9ec90e26-figure-01
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling .
17.1Vaginal Bleeding Inform postmenopausal women of the importance of reporting vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions (5.3) ] .
17.2Possible 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) ] .
17.3Possible Less Serious but 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.
17.4Instructions for Use of Applicator Step 1: Tear off a single applicator. Step 2: Separate the plastic wrap and remove the applicator from the plastic wrap as shown in Figure A. If after opening the package you see that the insert has come out of the applicator but has not fallen out of the package, carefully put it back into the applicator for insertion.
Please keep your hands clean and dry while handling the insert . Figure A Step 3: Hold the applicator so that the finger of one hand can press the applicator plunger as shown in Figure B. Figure B Step 4: Next select the best position for vaginal insertion of Yuvafem that is most comfortable for you.
See suggested reclining Figure C or standing Figure D position illustrated below: Figure C Figure D Step 5: Using the other hand, guide the applicator gently and comfortably through the vaginal opening (see Figures C and D above). If prior to insertion the insert falls out of the applicator, throw the insert and applicator away and use a new insert-filled applicator . Step 6: The applicator should be inserted (without forcing) as far as comfortably possible, or until half of the applicator is inside your vagina, whichever is less.
Step 7: Once the insert-filled applicator has been inserted, gently press the plunger until the plunger is fully depressed. This will eject the insert inside your vagina where it will dissolve slowly over several hours. Step 8: After depressing the plunger, gently remove the applicator and dispose of it the same way you would a plastic tampon applicator.
The applicator is of no further use and should be discarded properly. Insertion may be done at any time of the day. It is advisable to use the same time daily for all applications of Yuvafem (estradiol vaginal insert).
If you have any questions, please consult your healthcare provider or pharmacist. Manufactured for: AvKARE, Inc. Pulaski, TN 38478 YUVAFEM is a registered trademark of Amneal Pharmaceuticals LLC Mfg.
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