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Yuvafem Estradiol 10 ug Tablet, 18-count — NDC 42291-0962-18 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Yuvafem Estradiol 10 ug Tablet, 18-count — NDC 42291-962-18 (Billing 42291-0962-18)

by AvKARE · 18 APPLICATOR in 1 CARTON / 1 TABLET in 1 APPLICATOR

This is a package of 18 tablets of Yuvafem Estradiol 10 ug Tablet from AvKARE, marketed since Oct 2016 and currently FDA-listed.

NDC 42291-0962-18
🏷️ FDA NDC (as labeled) 42291-962-18 billing pads the product segment with a zero
This package
Contains18-count Pack sizes2 compare ↓
Also priced by: Part D plans $7.62/unit — full pricing hub ↓
Product page 42291-0962-08 Also comes in: 8 tablets 42291-962-08
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 42291-962-18 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
42291 labeler · 962 product · 18 package
Package marketed since
Oct 19, 2016
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
18 EA per package
Barcode (UPC-A, from the NDC)
3 4229196218 7
FDA record last changed
Jul 24, 2026
⚠️
Other active recalls for Estradiol (different manufacturers) — 4 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · May 12, 2026 — Defective Container; packets were found to be either empty or partially full. (ANI Pharmaceuticals, Inc.) · FDA recall D-0543-2026
Class III · May 16, 2024 — Failed Impurities/Degradation Specifications. (Zydus Pharmaceuticals (USA) Inc) · FDA recall D-0543-2024
Class III · May 16, 2024 — Failed Impurities/Degradation Specifications. (Zydus Pharmaceuticals (USA) Inc) · FDA recall D-0542-2024
Class III · Feb 21, 2023 — Failed Content Uniformity Specifications: The Spray Content Uniformity (SCU) requirement for Standard Deviation did not meet the requirement at the 18-month stability time point. (Padagis US LLC) · FDA recall D-0464-2023
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42291-962-18
Product NDC 42291-962
11-digit billing NDC 42291096218
NCPDP billing unit EA — each (per item)
RxCUI 884707, 1797113
UNII 4TI98Z838E
Application # ANDA205256
SPL Set ID d20abc9a-8f47-e274-c9b1-b71c9489761f
Established class (EPC) Estrogen
Mechanism of action Estrogen Receptor Agonists
Chemical class Estradiol Congeners
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-10-19
Route VAGINAL
Dosage form TABLET
Substance ESTRADIOL
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 55350020000310
GPI class Yuvafem
GCN Seq No 065966
GCN 28107
HICL code 001421
Ingredient (HICL) Estradiol
HIC1 code Q
Therapeutic class — broad (HIC1) Ear/Eye/Nose/Rectum/Topical/Vagina/Other
HIC2 code Q4
Therapeutic class — intermediate (HIC2) Vaginal Preparations
HIC3 code Q4K
Therapeutic class — specific (HIC3) Vaginal Estrogen Preparations
AHFS code 68:16.04.00
AHFS class Estrogens
FDB label name YUVAFEM 10 MCG VAGINAL INSERT
FDB brand name Yuvafem
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 065966
  • GCN: 28107
  • GPI-14 (Medi-Span): 55350020000310
  • HICL (First Databank): 001421
  • AHFS class code: 68:16.04.00
  • RxCUI (RxNorm): 884707
Why two NDCs? The FDA registers this code as 42291-962-18 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 42291-0962-18. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Radioactive Diagnostic Agent class.

Pharmacologic class Radioactive Diagnostic Agent, Estrogen
Drug family (ATC) Natural and semisynthetic estrogens, plain, Progestogens and estrogens, sequential preparations
How it works Positron Emitting Activity, Estrogen Receptor Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name YUVAFEM 10 MCG VAGINAL INSERT Ingredient Estradiol
📗 Our plain-language guide HelloPharmacist
  • It's an estrogen used mainly for menopause symptoms like hot flashes and vaginal dryness. Some patches are also used for low estrogen from ovarian problems or to prevent osteoporos...
  • That depends on the form. Patches go on the skin once or twice a week depending on the brand, and the injection goes into a muscle. Use the lowest dose that works for the shortest...
  • Headache, breast tenderness, spotting or irregular bleeding, cold-like symptoms and skin irritation where a patch sits are the most common. Tell your doctor if they bother you or d...
  • Get urgent help for chest pain, sudden weakness or trouble speaking, a swollen painful leg, sudden shortness of breath or sudden vision changes. These could be a stroke or blood cl...
📖 Read our full Estradiol guide →
5
Nutrient depletion considerations

Estradiol may be associated with lower levels of 5 nutrients — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Estradiol nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer 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
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
42291-0962-08 42291-962-08 Main listing 8 APPLICATOR in 1 CARTON / 1 TABLET in 1 APPLICATOR 2016-10-19 — Active
42291-0962-18 You're viewing this 18 APPLICATOR in 1 CARTON / 1 TABLET in 1 APPLICATOR 2016-10-19 — Active

Pack size FAQ

What quantity is in this package?
This is a 18-count package — 18 applicator in 1 carton / 1 tablet in 1 applicator.
How does this package differ from NDC 42291-0962-08?
Both are Yuvafem Estradiol 10 ug Tablet — the drug itself is identical. This page's package is the 18-count one, while NDC 42291-0962-08 is the 8 tablets package.
What NDC number is used to bill for this package of Yuvafem Estradiol 10 ug Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Estradiol 10 ug 00093-3223-08 Teva 8 inserts $5.518 AB Availability likely —
Estradiol Vaginal Inserts 10 ug 59651-0439-08 Aurobindo 1 tablet $5.518 AB Availability likely —
Yuvafem 10 ug 65162-0226-21 Amneal 8 tablets $5.518 AB Availability likely —
Estradiol Vaginal Inserts 10 ug 68462-0711-71 Glenmark 1 tablet $5.518 AB Availability likely —
Estradiol Vaginal Inserts 10 ug 72603-0874-08 NorthStar 1 tablet $5.518 AB Availability likely —
Vagifem 10 ug 00169-5176-03 Novo 8 inserts $20.325 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 —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2016
On the market since
Oct 2016
📍
2026
Currently FDA-listed
10 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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.

🧪 Avoiding an ingredient? See Estradiol inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerAvKARE
Application holderAMNEAL PHARMACEUTICALS
FDA applicationANDA205256 (ANDA)
Labeler code42291
First marketedOct 2016
Product typeHuman Prescription Drug
Portfolio384 products on file

More NDCs from AvKARE labeler code 42291

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🆘 Overdosage 🧬 Clinical Pharmacology 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📚 References 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage 29 words ▾

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 177 words ▾

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 55 words ▾

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 166 words ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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 116 words ▾

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 ~2 min read ▾

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 38 words ▾

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 ~3 min read ▾

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… [Excerpted — this section continues on DailyMed.]

📦 How Supplied / Storage and Handling 105 words ▾

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 144 words ▾

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 ~2 min read ▾

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.

Rev. 11-2017-03 AV 11/17 9ec90e26-figure-02 9ec90e26-figure-03 9ec90e26-figure-04 9ec90e26-figure-05

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Effects on Atrophic Vaginitis Yuvafem 10 mcg A 12-month double-blind, randomized, parallel group, placebo-controlled multicenter study was conducted in the U.S. and Canada to evaluate the efficacy and safety of Yuvafem 10 mcg in the treatment of atrophic vaginitis in 309 postmenopausal women between 46 and 81 years of age (mean 57.6 years of age) who at baseline identified their most bothersome symptom of atrophic vaginitis from among six symptoms (vaginal dryness, vaginal and/or vulvar irritation/itching, vaginal soreness, dysuria, dyspareunia and vaginal bleeding associated with intercourse).

Women inserted one insert intravaginally each day for 14 days, then one insert twice weekly for the remaining 50 weeks. The majority (92.9 percent) of the women were Caucasian (n=287), 3.2 percent were Black (n=10), 1.6 percent were Asian (n=5) and 2.2 percent were Other (n=7). All subjects were assessed for improvement in the mean change from baseline to Week 12 for co-primary efficacy variables of: a composite of most bothersome symptoms of atrophic vaginitis; percentage of vaginal superficial cells and percentage of vaginal parabasal cells on a vaginal smear; and vaginal pH.

Relief of Vaginal Symptoms Yuvafem 10 mcg was statistically superior to placebo in reducing the severity of a composite score of most bothersome symptoms associated with atrophic vaginitis at Week 12 (see Table 5). Table 5: Mean Change from Baseline to Week 12 in a Composite Score of Most Bothersome Symptoms Compared to Placebo – ITT Population a Placebo Yuvafem 10 mcg ITT Population a N 93 190 Baseline mean composite score 2.29

2.35Change from baseline at Week 12 (LOCF) -0.84 -1.20 p-value versus Placebo --- 0.002 a All randomized subjects who received at least one dose of study drug and had at least one post-baseline evaluation. Also demonstrated for Yuvafem 10 mcg compared to placebo was a statistically significant increase in the percentage of superficial cells at Week 12 (13.2 percent compared to 3.8 percent for matching placebo, p<0.001), a statistically significant decrease in parabasal cells at Week 12 (-37 percent compared to -9.3 percent for matching placebo, p<0.001), and a statistically significant mean reduction between baseline and Week 12 in vaginal pH score (-1.3 compared to -0.4 for matching placebo, p<0.001).

Endometrial safety was assessed by endometrial biopsy at the screening and final study visit. Of the 172 subjects in the Yuvafem 10 mcg group who had a biopsy performed at end of study, 92 subjects had endometrial tissue that was atrophic or inactive and 73 subjects had no tissue or tissue insufficient for diagnosis. There was one case of adenocarcinoma grade 2 and one case of complex hyperplasia without atypia.

Three subjects exhibited polyps (two atrophic polyps and one adenomyomatus type polyp) and two others had adenomyosis and an atypical epithelial proliferation. Endometrial safety of Yuvafem 10 mcg was additionally evaluated in a second, 12 month, open-label, multicenter safety study. Of the 297 subjects who had a biopsy performed at end of study, 183 subjects had endometrial tissue that was atrophic or inactive and 111 subjects had no tissue or tissue insufficient for diagnosis.

There was one case of complex hyperplasia without atypia. Two subjects exhibited polyps. Yuvafem 25 mcg A placebo-controlled comparison study was done in the U.S., in which 230 women were randomized to receive either placebo, Yuvafem 25 mcg or 10 mcg estradiol vaginal inserts.

Women inserted one insert intravaginally each day for 14 days, then one insert twice weekly for the remaining 10 weeks. All subjects were assessed for vaginal symptoms. Yuvafem 25 mcg was superior to placebo in reducing the severity of a composite score of symptoms associated with atrophic vaginitis (see Table 6).

An open-label, controlled comparison study was done in Canada in which 159 women were randomized to receive either Yuvafem 25 mcg or a comparator dr… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 35 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenicity, Mutagenicity, Impairment of Fertility 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.

📚 References ~1 min read ▾

15 REFERENCES Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA .

2007; 297:1465-1477. Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease.

Arch Int Med . 2006; 166:357-365. Curb JD, et al.

Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med . 2006; 166:772-780.

Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA .

2004; 292:1573-1580. Stefanick ML, et al. Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy.

JAMA . 2006; 295:1647-1657. Chlebowski RT, et al.

Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA . 2003; 289:3234-3253.

Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic cancers and Associated Diagnostic Procedures. JAMA .

2003; 290:1739-1748. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women.

JAMA . 2004; 291:2947-2958. Jackson RD, et al.

Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women’s Health Initiative Randomized Trial. J Bone Miner Res . 2006; 21:817-828.

Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women’s Health Initiative. Circulation .

2006; 113:2425-2434.

📄 Patient Package Insert ~3 min read ▾

FDA-Approved Patient Labeling Yuvafem® (estradiol vaginal inserts) Read this PATIENT INFORMATION before you start using Yuvafem and read what you get each time you refill your Yuvafem prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

What is the most important information I should know about Yuvafem (an estrogen hormone) 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 Yuvafem. Vaginal bleeding after menopause may be a warning sign of cancer in the uterus (womb).

Your healthcare provider should check any unusual vaginal bleeding to find out the cause. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dimentia (decline of 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 attack, strokes or dementia Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots Using estrogens with progestin may increase your chance of getting dementia, based on a study of women 65 years of age or older You and your healthcare provider should talk regularly about whether you still need treatment with Yuvafem What are Yuvafem?

Yuvafem are a medicine that contains estradiol (an estrogen hormone) in a vaginal insert. What are Yuvafem used for? Estradiol vaginal inserts are used after menopause to: Treat menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with Yuvafem to control these problems.

Who should not use Yuvafem? Do not start using Yuvafem if you: Have unusual vaginal bleeding Currently have or have had certain cancers 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 Yuvafem.

Had a stroke or heart attack Currently have or have had blood clots Currently have or have had liver problems Have been diagnosed with a bleeding disorder Are allergic to Yuvafem or any of its ingredients See the list of ingredients in Yuvafem at the end of this leaflet. Think you may be pregnant Tell your healthcare provider: If you have any unusual vaginal bleeding 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.

About all of your medical problems Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. About all the medicines you take This includes prescription and nonprescription medicines, vitamins and herbal supplements. Some medicines may affect how Yuvafem work.

Yuvafem may also affect how your other medicines work. If you are going to have surgery or will be on bed rest You may need to stop using Yuvafem. If you are breast feeding The hormone in Yuvafem can pass into your breast milk.

How should I use Yuvafem? Yuvafem is an insert that you place in your vagina with an applicator. Take the dose recommended by your healthcare provider and talk to him or her about how well that dose is working for you Estrogens should be used at the lowest dose possible for your treatment only as long as needed You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are using and whether you still need t… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 8 words ▾

• Warnings and Precautions, Malignant Neoplasms (5.3) 11/2017

📄 Package Label / Principal Display Panel 187 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL AvKARE NDC 42291- 962 -18 Yuvafem® (estradiol vaginal inserts, USP) 10 mcg 3 Blister packs each containing 6 vaginal inserts (with disposable applicators) 18 Vaginal Inserts (with disposable applicators) Rx only Contents: 18 vaginal inserts with disposable applicators. Each insert contains: estradiol, USP 10 mcg; corn starch, hypromellose, lactose monohydrate and magnesium stearate. The film coating contains hypromellose and polyethylene glycol.

Dosage: One (1) Yuvafem insert inserted vaginally once per day for two weeks, then one (1) insert inserted twice weekly (for example, Tuesday and Friday). Each insert is contained in a disposable single-use applicator. Please read the Patient Package Insert for complete product information.

Dispenser: This carton contains information intended for the patient. This information is to be provided to the patient with each package dispensed. Keep out of reach of children.

This package is not child-resistant. Store at 20° to 25° (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [ see USP Controlled Room Temperature]. Do not refrigerate.

Manufactured for: AvKARE, Inc. Pulaski, TN 38478 Mfg. Rev.

03-2018-05 AV 03/18 N3 42291 96218 7 Label Label 2

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Yuvafem — the program that covers self-administered drugs. 2 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Yuvafem. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$6.23M
Claims incl. refills
50.1K
Beneficiaries
39.6K
Spend / beneficiary
$157.15
Spend / claim
$124.26
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Estradiol — the ingredient across all brands.

Top reported reactions

Pain18,989
Pulmonary Embolism14,183
Injury11,633
Deep Vein Thrombosis11,586
Nausea11,321
Anxiety11,178
Headache10,251

Age at onset

Neonate62
Infant12
Child43
Adolescent475
Adult16,300
Elderly4,063

Reporter sex

187,988 reports
Male · 1%
Female · 99%
Unknown · 0%

Serious outcomes

Hospitalization42,755
Disabling5,947
Life-threatening5,296
Death3,354
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 9,564 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product
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.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by AvKARE. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 8 tablets (42291-0962-08). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
AvKARE is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 42291-0961-30 · AvKARE 42291-0965-90 · AvKARE →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.