Home › NDC Lookup › Ingredients › Estradiol › 50090-7987-00
🩹image loading
(from DailyMed)

Estradiol .0375 mg/d Patch, 4 pouches — NDC 50090-7987-0 (Billing 50090-7987-00)

by A-S Medication Solutions · 4 POUCH in 1 CARTON / 1 d in 1 POUCH

This is a package of 4 pouches of Estradiol .0375 mg/d Patch from A-S Medication Solutions, marketed since Aug 2006 and currently FDA-listed. It is this product's only package size.

NDC 50090-7987-00
🏷️ FDA NDC (as labeled) 50090-7987-0 billing pads the package segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 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

⚠️
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) 50090-7987-0
Product NDC 50090-7987
11-digit billing NDC 50090798700
NCPDP billing unit EA — each (per item)
RxCUI 403922
UNII 4TI98Z838E
Application # ANDA075182
SPL Set ID ba935918-39b3-4b56-bd83-78a29958e6d8
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 2006-08-09
Route TRANSDERMAL
Dosage form PATCH
Substance ESTRADIOL
TE code (Orange Book) AB2 · RLD · RS

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

GCN Seq No 052831
GCN 20069
HICL code 001421
Ingredient (HICL) Estradiol
HIC1 code G
Therapeutic class — broad (HIC1) Female Genital System
HIC2 code G1
Therapeutic class — intermediate (HIC2) Estrogens
HIC3 code G1A
Therapeutic class — specific (HIC3) Estrogenic Agents
AHFS code 68:16.04.00
AHFS class Estrogens
FDB label name ESTRADIOL 0.0375MG PATCH(1/WK)
FDB brand name Estradiol (Once Weekly)
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 052831
  • GCN: 20069
  • HICL (First Databank): 001421
  • AHFS class code: 68:16.04.00
  • RxCUI (RxNorm): 403922
Why two NDCs? The FDA registers this code as 50090-7987-0 — a 5-4-1 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 package segment → 50090-7987-00. 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 ESTRADIOL 0.0375MG PATCH(1/WK) Ingredient Estradiol
📖 What it is MedlinePlus · NLM

Transdermal estradiol (Climara®, Minivelle®, Vivelle-Dot®) is used to treat hot flashes (hot flushes; sudden feelings of mild or intense body heat) in women who are experiencing menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol (Climara®, Vivelle-Dot®) is also used to treat vaginal dryness, itching, and burning in women who are experiencing menopause. Transdermal estradiol (Climara®, Menostar®, Minivelle®, Vivelle-Dot®) is also used to prevent osteoporosis (a condition in which the bones become thin and weak and break easily) in women who are experiencing...

Read the full MedlinePlus article ↗
📗 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 $12.90 $51.61 / 4 d
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
50090-7987-00 You're viewing this Main listing 4 POUCH in 1 CARTON / 1 d in 1 POUCH 2026-06-03 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Estradiol .0375 mg/d 00378-4620-26 Mylan 8 patches $8.262 AB3 Availability likely —
Estradiol .0375 mg/d 00378-4643-26 Mylan 8 patches $8.262 AB1 Availability likely —
Estradiol .0375 mg/d 70710-1192-08 Zydus 8 patches $8.262 AB1 Availability likely —
Lyllana .0375 mg/d 65162-0148-08 Amneal 8 pouches $8.262 AB3 Availability likely —
Estradiol .0375 mg/d 68968-3437-08 Noven 8 pouches $8.262 AB3 Availability likely —
Dotti .0375 mg/d 65162-0992-08 Amneal 8 pouches $8.262 AB1 Availability likely —
Minivelle .0375 mg/d 68968-6637-08 Noven 8 pouches $11.584 AB3 Availability likely —
Estradiol .0375 mg/d 00378-3360-99 Mylan 4 patches $11.930 AB2 Availability likely —
Estradiol Transdermal System .0375 mg/d 00781-7122-54 Sandoz 4 patches $11.930 AB2 Availability likely —
Climara .0375 mg/d 50419-0456-04 Bayer 4 patches $18.298 AB2 Availability likely —
Vivelle-Dot .0375 mg/d 66758-0146-83 Sandoz 8 patches $18.376 AB1 Availability likely —
Estradiol .0375 mg/dthis 50090-7987-00 A-S 4 pouches — AB2 FDA listed —
estradiol .0375 mg/d 68382-0325-04 Zydus 4 patches — AB2 FDA listed —
estradiol .0375 mg/d 70771-1402-04 Zydus 4 patches — AB2 FDA listed —
Estradiol .0375 mg/d 70771-1564-08 Zydus 8 patches — AB1 FDA listed —
Estradiol .0375 mg/d 69238-1630-07 Amneal 8 pouches — AB1 FDA listed —
Estradiol .0375 mg/d 50090-7610-00 A-S 8 pouches — AB3 FDA listed —
Estradiol .0375 mg/d 00781-7138-40 Sandoz 24 patches — AB1 Discontinued —
Estradiol .0375 mg/d 69238-1293-07 Amneal 8 pouches — AB3 FDA listed —
Dotti .0375 mg/d 72162-2033-02 Bryant 8 pouches — AB1 FDA listed —
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

🏛️
2006
On the market since
Aug 2006
📍
2026
Currently FDA-listed
20 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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

LabelerA-S Medication Solutions
Application holderMYLAN TECHNOLOGIES INC
FDA applicationANDA075182 (ANDA)
Labeler code50090
First marketedAug 2006
Product typeHuman Prescription Drug
Portfolio2,811 products on file
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 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER Estrogen-Alone Therap y Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated to rule out malignancy in postmenopausal women with undiagnosed, persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ] .

Cardiovascular Disorders and Probable Dementia The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.3) ] . The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo.

It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5) , and Clinical Studies (14.4) ] . Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.3 , 14.4) ] . Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI.

Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.

Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia The WHI estrogen plus progestin substudy reported increased risks of 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 (5.1) , and Clinical Studies (14.3) ] .

The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.3) , Use in Specific Populations (8.5) , and Clinical Studies (14.4) ] . Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1 , 5.3) , and Clinical Studies (14.3 , 14.4) ] .

Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2) , and Clinical Studies (14.3) ] . Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen p… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Estradiol transdermal system continuous delivery (once-weekly) is indicated for: Estradiol transdermal system continuous delivery (once-weekly) is an estrogen indicated for: • Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) • Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) Limitations of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products. • Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure ( 1.3 ) • Prevention of Postmenopausal Osteoporosis ( 1.4 ) Limitations of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications.

Consider estrogen therapy only for women at significant risk of osteoporosis.

1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

1.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.

1.3Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure

1.4Prevention of Postmenopausal Osteoporosis Limitation of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women who have a history of endometriosis may need a progestogen [see Warnings and Precautions (5.2 , 5.14) ] .

Use estrogen-alone, or in combination with a progestogen at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. • Start therapy with estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day applied to the skin once-weekly. Dosage adjustment should be guided by the clinical response ( 2.1 ) • Place estradiol transdermal system continuous delivery (once-weekly) on a clean, dry area of the lower abdomen (below the umbilicus) or upper quadrant of the buttock.

Do not apply estradiol transdermal system continuous delivery (once-weekly) to the breasts ( 2.5 )

2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day applied to the skin once weekly. Make dosage adjustments based on the clinical response. Attempt to taper or discontinue estradiol transdermal system continuous delivery (once-weekly) at 3 to 6 month intervals.

2.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Start therapy with estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day applied to the skin once weekly. Make dosage adjustments based on the clinical response. Attempt to taper or discontinue estradiol transdermal system continuous delivery (once-weekly) at 3 to 6 month intervals.

2.3Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure Start therapy with 0.025 mg per day applied to the skin once weekly. Make dose adjustment based on the clinical response.

2.4Prevention of Postmenopausal Osteoporosis Start therapy with estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day applied to the skin once weekly.

2.5Application of the Estradiol Transdermal System Continuous Delivery (Once-Weekly) Site Selection • Place the adhesive side of estradiol transdermal system continuous delivery (once-weekly) on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. • Do not apply estradiol transdermal system continuous delivery (once-weekly) to or near the breasts. • Rotate the sites of application, with an interval of at least 1-week allowed between applications to the same site. • Select an area that is not oily, damaged, or irritated.

Avoid the waistline, since tight clothing may rub the transdermal system off. • Avoid application to areas where sitting would dislodge estradiol transdermal system continuous delivery (once-weekly). Application • Apply estradiol transdermal system continuous delivery (once-weekly) immediately after opening the pouch and removing the protective liner. • Press estradiol transdermal system continuous delivery (once-weekly) firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges. • If the system lifts, apply pressure to maintain adhesion. • In the event that a system falls off, reapply it to a different location.

If the old system cannot be reapplied, apply a new system for the remainder of the 7-day dosing interval. • Wear only one system at any one time during the 7-day dosing interval. • Swimming, bathing, or using a sauna while using estradiol transdermal system continuous delivery (once-weekly) has not been studied, and these activities may decrease the adhesion of the syst… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths ~3 min read ▾

3 DOSAGE FORMS AND STRENGTHS Estradiol Transdermal System, USP Continuous Delivery (Once-Weekly) is available as 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.06 mg/day, 0.075 mg/day or 0.1 mg/day of estradiol. • The 0.025 mg/day is available as a 7.75 cm 2 system containing estradiol, USP hemihydrate equivalent to 0.97 mg of estradiol for a nominal in vivo delivery of 0.025 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.025 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • The 0.0375 mg/day is available as an 11.625 cm 2 system containing estradiol, USP hemihydrate equivalent to 1.46 mg of estradiol for a nominal in vivo delivery of 0.0375 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.0375 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • The 0.05 mg/day is available as a 15.5 cm 2 system containing estradiol, USP hemihydrate equivalent to 1.94 mg of estradiol for a nominal in vivo delivery of 0.05 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.05 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • The 0.06 mg/day is available as an 18.6 cm 2 system containing estradiol, USP hemihydrate equivalent to 2.33 mg of estradiol for a nominal in vivo delivery of 0.06 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.06 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • The 0.075 mg/day is available as a 23.25 cm 2 system containing estradiol, USP hemihydrate equivalent to 2.91 mg of estradiol for a nominal in vivo delivery of 0.075 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.075 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • The 0.1 mg/day is available as a 31 cm 2 system containing estradiol, USP hemihydrate equivalent to 3.88 mg of estradiol for a nominal in vivo delivery of 0.1 mg of estradiol per day. Each patch consists of a round inner disk centered on a round peach color outer disk with “Estradiol 0.1 mg/day (Once-Weekly)” printed on the outer disk in brown.

Each patch is contained in a square, notched pouch with printed paper on both sides. The pouch is imprinted with the lot number and expiration date. • Transdermal system: 0.025 mg per day, 0.0375 mg per day, 0.05 mg per day, 0.06 mg per day, 0.075 mg per day and 0.1 mg per day ( 3 )

⛔ Contraindications ~1 min read ▾

4 CONTRAINDICATIONS Estradiol transdermal system continuous delivery (once-weekly) is contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2) ] • Breast cancer or history of breast cancer [see Warnings and Precautions (5.2) ] • Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ] • Active DVT, PE, or a history of these conditions [see Warnings and Precautions (5.1) ] • Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions [see Warnings and Precautions (5.1) ] • Known anaphylactic reaction, or angioedema, or hypersensitivity to estradiol transdermal system continuous delivery (once-weekly) • Hepatic impairment or disease • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders • Undiagnosed abnormal genital bleeding ( 4 , 5.2 ) • Breast cancer or a history of breast cancer ( 4 , 5.2 ) • Estrogen-dependent neoplasia ( 4 , 5.2 ) • Active DVT, PE or a history of these conditions ( 4 , 5.1 ) • Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions ( 4 , 5.1 ) • Known anaphylactic reaction, or angioedema, or hypersensitivity to estradiol transdermal system continuous delivery (once-weekly) ( 4 ) • Hepatic impairment or disease ( 4 , 5.10 ) • Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Estrogens increase the risk of gallbladder disease ( 5.4 ) • Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 ) • Monitor thyroid function in women on thyroid hormone replacement therapy ( 5.11 , 5.18 )

5.1Cardiovascular Disorders Increased risks of stroke and DVT are reported with estrogen-alone therapy. Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Immediately discontinue estrogen with or without progestogen therapy if any of these occur or are suspected.

Manage appropriately any risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus). Stroke The WHI estrogen-alone substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 strokes per 10,000 women-years, respectively).

The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.3) ] . Immediately discontinue estrogen-alone therapy if a stroke occurs or is suspected. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).

1 The WHI estrogen plus progestin substudy reported a statistically significant increased risk of stroke in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 strokes per 10,000 women years, respectively) [see Clinical Studies (14.3) ] . The increase in risk was demonstrated after the first year and persisted. 1 Immediately discontinue estrogen plus progestogen therapy if a stroke occurs or is suspected.

Coronary Heart Disease The WHI estrogen-alone substudy reported no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.3) ] . Subgroup analyses of women 50 to 59 years of age, who were less than 10 years since menopause, suggest a reduction (not statistically significant) of CHD events in those women receiving daily CE (0.625 mg)-alone compared to placebo (8 versus 16 per 10,000 women-years).

1 The WHI estrogen plus progestin substudy reported an increased risk (not statistically significant) of CHD events in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies (14.3) ] . In postmenopausal women with documented heart disease (n = 2,763), average 66.7 years of age, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit.

During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II.

Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the place… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Cardiovascular Disorders [see Boxed Warning , and Warnings and Precautions (5.1) ] • Malignant Neoplasms [see Boxed Warning , and Warnings and Precautions (5.2) ] The most common adverse reactions (≥ 10 percent) with estradiol transdermal system continuous delivery (once-weekly) are: breast pain, upper respiratory tract infections, headaches, abdominal pain, pain, and edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) 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. The data described below reflect pooled data from 5 clinical trials of estradiol transdermal system continuous delivery (once-weekly). A total of 614 women were exposed to estradiol transdermal system continuous delivery (once-weekly) for 3 months (193 women at 0.025 mg per day, 201 women at 0.05 mg per day, 194 women at 0.1 mg per day) in randomized, double-blind trials of clinical efficacy versus placebo and versus active comparator.

All women were postmenopausal, had a serum estradiol level of less than 20 pg/mL, and a minimum of five moderate to severe hot flushes per week or a minimum of 15 hot flushes per week of any severity at baseline. Included in this table are an additional 25 postmenopausal hysterectomized women exposed to estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day for 6 to 24 months (N = 16 at 24 months) in a randomized, double-blind, placebo-controlled study of estradiol transdermal system continuous delivery (once-weekly) for the prevention of osteoporosis.

Table 1: Treatment-Emergent Adverse Reactions Reported at a Frequency of ≥ 5 Percent and More Frequent in Women Receiving Estradiol Transdermal System Continuous Delivery (Once-Weekly) Estradiol Transdermal System Continuous Delivery (Once-Weekly) Body System Adverse Reactions 0.025 mg/day Adverse reactions occurring at rate of ≥ 5 percent in estradiol transdermal system continuous delivery (once-weekly) trials of clinical efficacy versus placebo and versus active comparator; and trial of estradiol transdermal system continuous delivery (once-weekly) versus placebo for the prevention of osteoporosis (N = 219) 0.05 mg/day Adverse reactions occurring at rate of ≥ 5 percent in estradiol transdermal system continuous delivery (once-weekly) trials of clinical efficacy versus placebo and versus active comparator (N = 201) 0.1 mg/day (N = 194) Placebo Adverse reactions occurring in placebo group in estradiol transdermal system continuous delivery (once-weekly) trial of clinical efficacy versus placebo (N = 72) Body as a Whole Headache Pain Back Pain Edema 21% 5% 1% 4% 0.5% 39% 18% 8% 8% 13% 37% 13% 11% 9% 10% 29% 10% 7% 6% 6% Digestive System Abdominal Pain Nausea Flatulence 9% 0% 1% 1% 21% 11% 5% 3% 29% 16% 6% 7% 18% 8% 3% 1% Musculoskeletal System Arthralgia 7% 1% 9% 5% 11% 5% 4% 3% Nervous System Depression 13% 1% 10% 5% 11% 8% 1% 0% Urogenital System Breast Pain Leukorrhea 12% 5% 1% 18% 8% 6% 41% 29% 7% 11% 4% 1% Respiratory System URTI Pharyngitis Sinusitis Rhinitis 15% 6% 0.5% 4% 2% 26% 17% 3% 4% 4% 29% 17% 7% 5% 6% 14% 8% 3% 3% 1% Skin and Appendages Pruritus 19% 0.5% 12% 6% 12% 3% 15% 6%

6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of estradiol transdermal system continuous delivery (once-weekly). 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 Changes in bleeding pattern, pelvic pain… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 115 words ▾

7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St.

John’s wort (hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. • Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.

( 7 )

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Estradiol transdermal system continuous delivery (once-weekly) is not indicated for use in pregnancy. There are no data with the use of estradiol transdermal system continuous delivery (once-weekly) in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

8.2Lactation Risk Summary Estrogens are present in human milk and can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for estradiol transdermal system continuous delivery (once-weekly) and any potential adverse effects on the breastfed child from estradiol transdermal system continuous delivery (once-weekly) or from the underlying maternal condition.

8.4Pediatric Use In general, estradiol transdermal system continuous delivery (once-weekly) is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population. If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone metabolism and effects on epiphyseal centers is recommended during estrogen administration.

8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol transdermal system continuous delivery (once-weekly) to determine whether those over 65 years of age differ from younger subjects in their response to estradiol transdermal system continuous delivery (once-weekly). 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 (14.3) ] .

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 (14.3) ] . 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 (5.3) , and Clinical Studies (14.4) ] .

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 (5.3) , and Clinical Studies (14.4) ] .

🤰 Pregnancy 100 words ▾

8.1Pregnancy Risk Summary Estradiol transdermal system continuous delivery (once-weekly) is not indicated for use in pregnancy. There are no data with the use of estradiol transdermal system continuous delivery (once-weekly) in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

🧒 Pediatric Use 56 words ▾

8.4Pediatric Use In general, estradiol transdermal system continuous delivery (once-weekly) is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population. If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone metabolism and effects on epiphyseal centers is recommended during estrogen administration.

🧓 Geriatric Use 219 words ▾

8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing estradiol transdermal system continuous delivery (once-weekly) to determine whether those over 65 years of age differ from younger subjects in their response to estradiol transdermal system continuous delivery (once-weekly). 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 (14.3) ] .

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 (14.3) ] . 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 (5.3) , and Clinical Studies (14.4) ] .

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 (5.3) , and Clinical Studies (14.4) ] .

🆘 Overdosage 41 words ▾

10 OVERDOSAGE Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding in women. Treatment of overdose consists of discontinuation of estradiol transdermal system continuous delivery (once-weekly) 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, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.

To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism.

Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to estradiol transdermal system continuous delivery (once-weekly) nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.

12.3Pharmacokinetics Absorption Transdermal administration of estradiol transdermal system continuous delivery (once-weekly) produces mean serum concentrations of estradiol comparable to those produced by premenopausal women in the early follicular phase of the ovulatory cycle. The pharmacokinetics of estradiol following application of the estradiol transdermal system continuous delivery (once-weekly) were investigated in 197 healthy postmenopausal women in six studies. In five of the studies, the estradiol transdermal system continuous delivery (once-weekly) was applied to the abdomen, and in a sixth study, application to the buttocks and abdomen were compared.

The estradiol transdermal system continuous delivery (once-weekly) continuously releases estradiol which is transported across intact skin leading to sustained circulating levels of estradiol during a 7-day treatment period. The systemic availability of estradiol after transdermal administration is about 20 times higher than that after oral administration. This difference is due to the absence of first pass metabolism when estradiol is given by the transdermal route.

In a bioavailability study, the estradiol transdermal system continuous delivery (once-weekly) 7.75 cm 2 was studied with the estradiol transdermal system continuous delivery (once-weekly) 15.5 cm 2 as reference. The mean estradiol levels in serum from the two sizes are shown in Figure 1. Figure 1: Mean Serum 17b - Estradiol Concentrations versus Time Profile following Application of a 7.75 cm 2 Transdermal System and Application of a 15.5 cm 2 Estradiol Transdermal System Continuous Delivery (Once-Weekly) Dose proportionality was demonstrated for the estradiol transdermal system continuous delivery (once-weekly) 7.75 cm 2 as compared to the estradiol transdermal system continuous delivery (once-weekly) 15.5 cm 2 in a 2-week crossover study with a 1-week washout period between the two-transdermal systems in 24 postmenopausal women.

Dose proportionality was also demonstrated for the estradiol transdermal system continuous delivery (once-weekly) (15.5 cm 2 and 31 cm 2 ) in a 1-week study conducted in 54 postmenopausal women. The mean steady state levels (C avg ) of the estradiol during the application of estradiol tra… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 188 words ▾

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, which is secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.

To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and FSH, through a negative feedback mechanism.

Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

📦 How Supplied / Storage and Handling 19 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-7987 NDC: 50090-7987-0 1 d in a POUCH / 4 in a CARTON

📋 Description ~1 min read ▾

11 DESCRIPTION Estradiol transdermal system, USP continuous delivery (once-weekly) is designed to release estradiol continuously upon application to intact skin. Six (7.75, 11.625, 15.5, 18.6, 23.25 and 31 cm 2 ) systems are available to provide nominal in vivo delivery of 0.025, 0.0375, 0.05, 0.06, 0.075 or 0.1 mg respectively of estradiol per day. The period of use is 7 days.

Each system has a contact surface area of either 7.75, 11.625, 15.5, 18.6, 23.25 or 31 cm 2 , and contains estradiol, USP hemihydrate equivalent to 0.97, 1.46, 1.94, 2.33, 2.91 or 3.88 mg of estradiol, respectively. The composition of the systems per unit area is identical. Estradiol, USP hemihydrate is a white, crystalline powder, chemically described as Estra-1,3,5(10)-triene-3,17β-diol-hemihydrate.

It has a molecular formula of C 18 H 24 O 2 • ½ H 2 O and molecular weight of 281.39. The structural formula is: Meets USP Drug Release Test 2. The estradiol transdermal system continuous delivery (once-weekly) comprises four layers.

Proceeding from the visible surface toward the surface attached to the skin, these layers are: (1) A foam backing with adhesive layer (2) A polyester film (3) An acrylate adhesive matrix containing estradiol. (4) A protective liner of siliconized polyester film is attached to the adhesive surface and must be removed before the system can be used. The active component of the transdermal system is estradiol.

The remaining components of the transdermal system (propylene glycol, povidone, anhydrous colloidal silicon dioxide, pressure sensitive acrylic adhesive, copolymer foam, polyester film, and brown ink) are pharmacologically inactive. Estradiol Structural Formula Transdermal Parts

💬 Information for Patients 113 words ▾

17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warning and Precautions (5.2) ] . Possible Serious Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.1 , 5.2 , 5.3) ] .

Possible Common Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen-alone therapy such as headache, breast pain and tenderness, nausea and vomiting.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Transdermal administration of estradiol transdermal system continuous delivery (once-weekly) produces mean serum concentrations of estradiol comparable to those produced by premenopausal women in the early follicular phase of the ovulatory cycle. The pharmacokinetics of estradiol following application of the estradiol transdermal system continuous delivery (once-weekly) were investigated in 197 healthy postmenopausal women in six studies. In five of the studies, the estradiol transdermal system continuous delivery (once-weekly) was applied to the abdomen, and in a sixth study, application to the buttocks and abdomen were compared.

The estradiol transdermal system continuous delivery (once-weekly) continuously releases estradiol which is transported across intact skin leading to sustained circulating levels of estradiol during a 7-day treatment period. The systemic availability of estradiol after transdermal administration is about 20 times higher than that after oral administration. This difference is due to the absence of first pass metabolism when estradiol is given by the transdermal route.

In a bioavailability study, the estradiol transdermal system continuous delivery (once-weekly) 7.75 cm 2 was studied with the estradiol transdermal system continuous delivery (once-weekly) 15.5 cm 2 as reference. The mean estradiol levels in serum from the two sizes are shown in Figure 1. Figure 1: Mean Serum 17b - Estradiol Concentrations versus Time Profile following Application of a 7.75 cm 2 Transdermal System and Application of a 15.5 cm 2 Estradiol Transdermal System Continuous Delivery (Once-Weekly) Dose proportionality was demonstrated for the estradiol transdermal system continuous delivery (once-weekly) 7.75 cm 2 as compared to the estradiol transdermal system continuous delivery (once-weekly) 15.5 cm 2 in a 2-week crossover study with a 1-week washout period between the two-transdermal systems in 24 postmenopausal women.

Dose proportionality was also demonstrated for the estradiol transdermal system continuous delivery (once-weekly) (15.5 cm 2 and 31 cm 2 ) in a 1-week study conducted in 54 postmenopausal women. The mean steady state levels (C avg ) of the estradiol during the application of estradiol transdermal system continuous delivery (once-weekly) 31 cm 2 and 15.5 cm 2 on the abdomen were about 80 and 40 pg/mL, respectively. In a 3-week multiple application study in 24 postmenopausal women, the 31 cm 2 estradiol transdermal system continuous delivery (once-weekly) produced average peak estradiol concentrations (C max ) of approximately 100 pg/mL.

Trough values at the end of each wear interval (C min ) were approximately 35 pg/mL. Nearly identical serum curves were seen each week, indicating little or no accumulation of estradiol in the body. Serum estrone peak and trough levels were 60 and 40 pg/mL, respectively.

In a single dose, randomized, crossover study conducted to compare the effect of site of application, 38 postmenopausal women wore a single estradiol transdermal system continuous delivery (once-weekly) 31 cm 2 for 1 week on the abdomen and buttocks. The estradiol serum concentration profiles are shown in Figure 2. Values of C max and C avg were, respectively, 25 percent and 17 percent higher with the buttock application than with the abdomen application.

Figure 2: Observed Mean (± SE) Estradiol Serum Concentrations for a One Week Application of the Estradiol Transdermal System Continuous Delivery (Once-Weekly) (31 cm 2 ) to the Abdomen and Buttocks of 38 Postmenopausal Women Table 2 provides a summary of estradiol pharmacokinetic parameters determined during evaluation of the estradiol transdermal system continuous delivery (once-weekly). Table 2: Pharmacokinetic Summary (Mean Estradiol Values) Estradiol Delivery Rate Surface Area (cm 2 ) Application Site No. of Subjects Dosing C max (pg/mL) C min (pg/mL) C ave (pg/mL) 0.025

7.75Abdomen 24 Single 32 17 22 0.05

15.5Abdomen 102… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 48 words ▾

12.2Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to estradiol transdermal system continuous delivery (once-weekly) nor her risk for adverse outcomes. Likewise, exposure comparisons across different estrogen products to infer efficacy or safety for the individual woman may not be valid.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Effects on Vasomotor Symptoms in Postmenopausal Women A study of 214 women 25 to 74 years of age met the qualification criteria and were randomly assigned to one of the three treatment groups: 72 to the 0.05 mg estradiol patch, 70 to the 0.1 mg estradiol patch, and 72 to placebo. Potential participants were postmenopausal women in good general health who experienced vasomotor symptoms. Natural menopause patients had not menstruated for at least 12 months and surgical menopause patients had undergone bilateral oophorectomy at least 4 weeks before evaluation for study entry.

In order to enter the 11-week treatment phase of the study, potential participants must have experienced a minimum of five moderate to severe hot flushes per week, or a minimum of 15 hot flushes of any severity per week, for 2 consecutive weeks. Women wore the patches in a cyclical fashion (three weeks on and one week off). During treatment, all women used diaries to record the number and severity of hot flushes.

Women were monitored by clinic visits at the end of weeks 1, 3, 7, and 11 and by telephone at the end of weeks 4, 5, 8, and 9. Adequate data for the analysis of efficacy was available from 191 subjects. The results are presented as the mean ± SD number of flushes in each of the 3 treatment weeks of each 4-week cycle.

In the 0.05 mg estradiol group, the mean weekly hot flush rate across all treatment cycles decreased from 46 ± 6.5 at baseline to 20 ± 3 (-67 percent). The 0.1 mg estradiol group had a decline in the mean weekly hot flush rate from 52 ± 4.4 at baseline to 16 ± 2.4 (-72 percent). In the placebo group, the mean weekly hot flush rate declined from 53 ± 4.5 at baseline to 46 ± 6.5 (-18.1 percent).

Compared with placebo, the 0.05 mg and 0.1 mg estradiol groups showed a statistically significantly larger mean decrease in hot flushes across all treatment cycles (P < 0.05). When the response to treatment was analyzed for each of the three cycles of therapy, similar statistically significant differences were observed between both estradiol treatment groups and the placebo group during all treatment cycles. In a double-blind, placebo-controlled, randomized study of 187 women receiving estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day or placebo continuously for up to three 28-day cycles, the estradiol transdermal system continuous delivery (once-weekly) 0.025 mg per day dosage was shown to be statistically better than placebo at weeks 4 and 12 for relief of both the frequency and severity of moderate to severe vasomotor symptoms.

Table 3: Mean Change from Baseline in the Number of Moderate to Severe Vasomotor Symptoms Intent to Treat (ITT) Treatment Group Statistics Week 4 Week 8 Week 12 E 2 Transdermal System N 82 84 68 Mean -6.45 -7.69 -7.56 SD 4.65 4.76

4.64Placebo N 83 71 65 Mean -5.11 -5.98 -5.98 SD 7.43 8.63 9.69 p-value < 0.002 < 0.003 A second active-control trial of 193 randomized women was supportive of the placebo-controlled trial.

14.2Effects on Bone Mineral Density in Postmenopausal Women A two-year clinical trial enrolled a total of 175 healthy, hysterectomized, postmenopausal, non-osteoporotic (that is, lumbar spine bone mineral density > 0.9 gm/ cm 2 ) women at 10 study centers in the United States. A total of 129 participating women were allocated to receive active treatment with 4 different doses of estradiol patches (7.75, 15.5, 18.6, 31 cm 2 ) and 46 participating women were allocated to receive placebo patches. Seventy-seven percent of the randomized women (100 on active drug and 34 on placebo) contributed data to the analysis of percent change of anterior-posterior (A-P) spine BMD, the primary efficacy variable (see Figure 3).

A statistically significant overall treatment effect at each timepoint was noted, implying bone preservation for all active treatment groups at all timepoints, as opposed to bone loss for placebo at all timepoints. Figure 3: Mean Percent Change f… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 35 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, 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.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 32 words ▾

13.1Carcinogenesis, Mutagenesis, 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 219 words ▾

15 REFERENCES 1. Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause.

JAMA . 2007;297:1465-1477. 2.

Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med.

2006;166:357-365. 3. Curb JD, et al.

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

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

JAMA . 2004;292:1573-1580. 5.

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. 6. Chlebowski RT, et al.

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

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

JAMA . 2003;290:1739-1748. 8.

Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA .

2004;291:2947-2958. 9. 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.

10. 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 ▾

Patient Information Estradiol Transdermal System, USP Continuous Delivery (Once-Weekly) (esʺ tra dyeʹ ol) Read this Patient Information before you start using estradiol transdermal system continuous delivery (once-weekly) and each time you get a refill. 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 estradiol transdermal system continuous delivery (once-weekly) (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 estradiol transdermal system continuous delivery (once-weekly). 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. • Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function). • Using estrogen-alone may increase your chances of getting strokes or blood clots. • Using estrogen-alone may increase your chance of getting dementia, based on a study of women age 65 years of age and older. • Do not use estrogens with progestogens to prevent heart disease, heart attacks, strokes or dementia. • Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. • Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women age 65 years of age and older. • Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia.

Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of estradiol transdermal system continuous delivery (once-weekly) will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with estradiol transdermal system continuous delivery (once-weekly).

What is estradiol transdermal system continuous delivery (once-weekly)? Estradiol transdermal system continuous delivery (once-weekly) is a prescription medicine patch (transdermal system) that contains estradiol (an estrogen hormone). What is estradiol transdermal system continuous delivery (once-weekly) used for?

The estradiol transdermal system continuous delivery (once-weekly) is used after menopause to: • Reduce moderate to severe hot flashes Estrogens are hormones made by a woman’s ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the “change of life” or menopause (the end of monthly menstrual periods).

Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes “surgical menopause.” When estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating (“hot flashes” or “hot flushes”). In some women, the symptoms are mild, and they will not need to use estrogens.

In other women, symptoms can be more severe. • Treat moderate to severe menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with estradiol transdermal system continuous delivery (once-weekly) to control these problems. If you use estradiol transdermal system continuous delivery (once-weekly) only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 3 words ▾

estradiol Label Image

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 Estradiol — the program that covers self-administered drugs. 17 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 Estradiol. 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
$65.73M
Claims incl. refills
1.4M
Beneficiaries
1.2M
Spend / beneficiary
$56.27
Spend / claim
$46.97
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.

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 — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 A-S Medication Solutions. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
A-S Medication Solutions 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.
← 50090-7986-00 · A-S 50090-7988-00 · A-S →
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.