estradiol .05 mg/d Patch
Other active recalls for Estradiol (different manufacturers) — 4 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Radioactive Diagnostic Agent class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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 ↗- Estradiol is a form of estrogen — the main female sex hormone. When estrogen levels fall after menopause (or due to other conditions like ovarian failure), you can get symptoms lik...
- What exactly is estradiol and why has my doctor prescribed it?
- Apply the patch to a clean, dry area of skin — usually the lower abdomen. Never put it on your breasts. Press it firmly in place and leave it on for the full wear period — once a w...
- How do I use my estradiol patch correctly?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Estradiol — tap one for details:
Estradiol may be associated with lower levels of 5 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII HR49R9S6XG
A synthetic polymer ingredient used as a film-former and binder in tablet coatings and sustained-release formulations. It helps create a protective layer around the medication to control how and when the drug releases in the body.
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UNII 25GT92NY0C
A synthetic polymer made from acrylic compounds. It's used in tablet coatings and film formulations to help protect the medicine and control how quickly it dissolves in the body.
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UNII Z2Z439864Y
Ethyl oleate is a clear liquid derived from oleic acid, a natural fatty acid. In medicines, it acts as a solvent and penetration enhancer, helping dissolve active ingredients and improve their absorption through the skin or mucous membranes.
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UNII Y98611C087
Glyceryl laurate is an emulsifier made by combining glycerin and lauric acid. It helps mix oil and water-based ingredients together in the medicine and may improve how the product feels or spreads.
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UNII R8WN29J8VF
Glycidyl methacrylate is a synthetic chemical compound used as a coating or binding agent in pharmaceutical formulations. It helps form protective shells around tablets or capsules and can improve how ingredients stick together in the finished product.
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UNII 0RE8K4LNJS
Isopropyl myristate is an oily liquid made from coconut or palm oil. It's used in medicines as an emollient and penetration enhancer to help the medicine absorb through skin or improve spreadability in topical products.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII L9MK238N77
Vinyl acetate is a synthetic polymer used primarily as a film-coating agent in tablets and capsules. It helps create a smooth, protective outer layer that controls how quickly the medicine dissolves and improves appearance.
9 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $12.90 | $51.61 / 4 patch |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Estradiol .05 mg/d 00378-4621-26 | Mylan | 8 patches | $8.222 | AB3 | Availability likely | — |
| Dotti .05 mg/d 65162-0993-08 | Amneal | 8 pouches | $8.222 | AB1 | Availability likely | — |
| Estradiol .05 mg/d 00378-4642-26 | Mylan | 8 patches | $8.222 | AB1 | Availability likely | — |
| Estradiol .05 mg/d 70710-1193-08 | Zydus | 8 patches | $8.222 | AB1 | Availability likely | — |
| Lyllana .05 mg/d 65162-0149-08 | Amneal | 8 pouches | $8.222 | AB3 | Availability likely | — |
| Estradiol .05 mg/d 68968-3450-08 | Noven | 8 pouches | $8.222 | AB3 | Availability likely | — |
| Estradiol .05 mg/d 00378-3350-99 | Mylan | 4 patches | $10.803 | AB2 | Availability likely | — |
| Estradiol Transdermal System .05 mg/d 00781-7133-54 | Sandoz | 4 patches | $10.803 | AB2 | Availability likely | — |
| Minivelle .05 mg/d 68968-6650-08 | Noven | 8 pouches | $11.587 | AB3 | Availability likely | — |
| Climara .05 mg/d 50419-0451-04 | Bayer | 4 patches | $18.269 | AB2 | Availability likely | — |
| Vivelle-Dot .05 mg/d 66758-0147-83 | Sandoz | 8 patches | $18.403 | AB1 | Availability likely | — |
| Estradiol .05 mg/d 50090-7611-00 | A-S | 4 patches | — | AB2 | FDA listed | — |
| estradiol .05 mg/dthis 68382-0326-04 | Zydus | 4 patches | — | AB2 | FDA listed | — |
| estradiol .05 mg/d 70771-1403-04 | Zydus | 4 patches | — | AB2 | FDA listed | — |
| Estradiol .05 mg/d 70771-1565-08 | Zydus | 8 patches | — | AB1 | FDA listed | — |
| Estradiol .05 mg/d 00781-7144-40 | Sandoz | 24 patches | — | AB1 | Discontinued | — |
| Estradiol .05 mg/d 69238-1295-07 | Amneal | 8 pouches | — | AB3 | FDA listed | — |
| Estradiol .05 mg/d 69238-1631-07 | Amneal | 8 pouches | — | AB1 | FDA listed | — |
| Dotti .05 mg/d 72162-2034-02 | Bryant | 8 pouches | — | AB1 | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68382-0326-04 You're viewing this | 4 POUCH in 1 CARTON (68382-326-04) / 1 PATCH in 1 POUCH (68382-326-01) / 7 d in 1 PATCH | 2023-11-02 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated to rule out malignancy in postmenopausal women with undiagnosed, persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5 .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…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Estradiol Transdermal System is indicated for: Estradiol Transdermal System, USP 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 ▾
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 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 on a clean, dry area of the lower abdomen (below the umbilicus) or upper quadrant of the buttock. Do not apply Estradiol Transdermal System to the breasts ( 2.5 )
2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with Estradiol Transdermal System 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 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 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 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 0.025 mg per day applied to the skin once weekly.
2.5Application of the Estradiol Transdermal System Site Selection Place the adhesive side of Estradiol Transdermal System on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. Do not apply Estradiol Transdermal System 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.
Application Apply Estradiol Transdermal System immediately after opening the pouch and removing the protective liner. Press Estradiol Transdermal System 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 has not been studied, and these activities may decrease the adhesion of the system and the delivery of estradiol.
2.6Removal of the Estradiol Transdermal System Remove Estradiol Transdermal System carefully and slowly to avoid irritation of the skin. If any adhesive remains on the skin after removal of Estradiol Transdermal System, allow the area to dry for 15 minutes and then gently rub the area with an oil-based cream or lotion to remove the adhesive residue. Used patches still contain some active hormones.
Carefully fold each patch in half so that it sticks to itself before throwing it away.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Estradiol Transdermal System, 0.025 mg/day — each 7.5 cm 2 system contains 1.888 mg of estradiol USP Estradiol Transdermal System, 0.0375 mg/day — each 11.25 cm 2 system contains 2.832 mg of estradiol USP Estradiol Transdermal System, 0.05 mg/day — each 15 cm 2 system contains 3.777 mg of estradiol USP Estradiol Transdermal System, 0.06 mg/day — each 18 cm 2 system contains 4.532 mg of estradiol USP Estradiol Transdermal System, 0.075 mg/day — each 22.5 cm 2 system contains 5.665 mg of estradiol USP Estradiol Transdermal System, 0.1 mg/day — each 30 cm 2 system contains 7.553 mg of estradiol USP 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 ▾
4 CONTRAINDICATIONS Estradiol Transdermal System 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 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 ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
⚠️ Warnings and Cautions ▾
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 placebo g…
🤒 Adverse Reactions ▾
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 are breast pain, upper respiratory tract infections, headaches, abdominal pain, pain, and edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 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. A total of 614 women were exposed to Estradiol Transdermal System 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 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 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 a) Adverse reactions occurring at rate of ≥5 percent in Estradiol Transdermal System trials of clinical efficacy versus placebo and versus active comparator; and trial of Estradiol Transdermal System versus placebo for the prevention of osteoporosis b) Adverse reactions occurring at rate of ≥5 percent in Estradiol Transdermal System trials of clinical efficacy versus placebo and versus active comparator c) Adverse reactions occurring in placebo group in Estradiol Transdermal System trial of clinical efficacy versus placebo Estradiol Transdermal System Body System Adverse Reactions 0.025 mg/day a (N=219) 0.05 mg/day b (N=201) 0.1 mg/day b (N=194) Placebo c (N=72) Body as a Whole 21% 39% 37% 29% Headache 5% 18% 13% 10% Pain 1% 8% 11% 7% Back Pain 4% 8% 9% 6% Edema 0.5% 13% 10% 6% Digestive System 9% 21% 29% 18% Abdominal Pain 0% 11% 16% 8% Nausea 1% 5% 6% 3% Flatulence 1% 3% 7% 1% Musculoskeletal System 7% 9% 11% 4% Arthralgia 1% 5% 5% 3% Nervous System 13% 10% 11% 1% Depression 1% 5% 8% 0% Urogenital System 12% 18% 41% 11% Breast Pain 5% 8% 29% 4% Leukorrhea 1% 6% 7% 1% Respiratory System 15% 26% 29% 14% URTI 6% 17% 17% 8% Pharyngitis 0.5% 3% 7% 3% Sinusitis 4% 4% 5% 3% Rhinitis 2% 4% 6% 1% Skin and Appendages 19% 12% 12% 15% Pruritus 0.5% 6% 3% 6%
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of Estradiol Transdermal System. 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 Breast Breast cancer, breast pain, breast tenderness Cardiovascular Changes in blood pressure, palpitations, hot flashes Gastrointestinal Vomiting, abdominal pain, abdominal distension, nausea Skin Alopecia, hyperhidrosis, night sweats, urticaria, rash Eyes Visual disturbances, contact lens intolerance, Central Nervous System Depression, migraine, paresthesia, dizziness, anxiety, irritability, mood…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St.
John's wort (hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Estradiol Transdermal System is not indicated for use in pregnancy. There are no data with the use of Estradiol Transdermal System 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 and any potential adverse effects on the breastfed child from Estradiol Transdermal System or from the underlying maternal condition.
8.4Pediatric Use In general, Estradiol Transdermal System 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 to determine whether those over 65 years of age differ from younger subjects in their response to Estradiol Transdermal System. 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 ▾
8.1Pregnancy Risk Summary Estradiol Transdermal System is not indicated for use in pregnancy. There are no data with the use of Estradiol Transdermal System in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use In general, Estradiol Transdermal System 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 ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing Estradiol Transdermal System to determine whether those over 65 years of age differ from younger subjects in their response to Estradiol Transdermal System. 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 ▾
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 therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, 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 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 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 were investigated in 197 healthy postmenopausal women in six studies. In five of the studies, the Estradiol Transdermal System was applied to the abdomen and in a sixth study, application to the buttocks and abdomen were compared.
The Estradiol Transdermal System 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, 0.025 mg per day was studied with the Estradiol Transdermal System, 0.05 mg per day as reference. The mean estradiol levels in serum from the two sizes are shown in Figure 1. Figure 1: Mean Serum 17ß-Estradiol Concentrations versus Time Profile following Application of a 0.025 mg per day Transdermal System and Application of a 0.05 mg per day Estradiol Transdermal System Dose proportionality was demonstrated for the Estradiol Transdermal System 0.025 mg per day as compared to the Estradiol Transdermal System 0.05 mg per day 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 (0.05 mg per day and 0.1 mg per day) 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 0.1 mg per day and 0.05 mg per day on the abdomen were about 80 and 40 pg/mL, respectively. In a 3-week multiple application study in 24 postmenopausal women, the 0.1 mg per day Estradiol Transdermal System produced average peak estradiol concentrations (C max ) of approximately 100 pg/mL.
Trough values at…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, 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 ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Estradiol Transdermal System, USP, 0.025 mg / day — each 7.5 cm 2 system contains 1.888 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-324-04 Estradiol Transdermal System, USP, 0.0375 mg / day — each 11.25 cm 2 system contains 2.832 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-325-04 Estradiol Transdermal System, USP, 0.05 mg / day — each 15 cm 2 system contains 3.777 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-326-04 Estradiol Transdermal System, USP, 0.06 mg / day — each 18 cm 2 system contains 4.532 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-327-04 Estradiol Transdermal System, USP, 0.075 mg / day — each 22.5 cm 2 system contains 5.665 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-328-04 Estradiol Transdermal System, USP, 0.1 mg / day — each 30 cm 2 system contains 7.553 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-329-04
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP for Controlled Room Temperature]. Do not store unpouched. Do not store above 86°F (30°C).
Apply immediately upon removal from the protective pouch. Used transdermal systems still contain active hormone. To discard, fold the sticky side of the transdermal system together, place it in a sturdy child-proof container, and place this container in the trash.
Used transdermal systems should not be flushed in the toilet.
16.1How Supplied Estradiol Transdermal System, USP, 0.025 mg / day — each 7.5 cm 2 system contains 1.888 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-324-04 Estradiol Transdermal System, USP, 0.0375 mg / day — each 11.25 cm 2 system contains 2.832 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-325-04 Estradiol Transdermal System, USP, 0.05 mg / day — each 15 cm 2 system contains 3.777 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-326-04 Estradiol Transdermal System, USP, 0.06 mg / day — each 18 cm 2 system contains 4.532 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-327-04 Estradiol Transdermal System, USP, 0.075 mg / day — each 22.5 cm 2 system contains 5.665 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-328-04 Estradiol Transdermal System, USP, 0.1 mg / day — each 30 cm 2 system contains 7.553 mg of estradiol USP Individual Carton of 4 systems………………NDC 68382-329-04
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP for Controlled Room Temperature]. Do not store unpouched. Do not store above 86°F (30°C).
Apply immediately upon removal from the protective pouch. Used transdermal systems still contain active hormone. To discard, fold the sticky side of the transdermal system together, place it in a sturdy child-proof container, and place this container in the trash.
Used transdermal systems should not be flushed in the toilet.
📋 Description ▾
11 DESCRIPTION Estradiol Transdermal System, USP is designed to release estradiol continuously upon application to intact skin. Six (7.5, 11.25, 15, 18, 22.5 and 30 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 7.5, 11.25, 15, 18, 22.5 or 30 cm 2 , and contains 1.888, 2.832, 3.777, 4.532, 5.665 or 7.553 mg of estradiol USP respectively. The composition of the systems per unit area is identical. Estradiol USP is a white or creamy white, small crystals or crystalline powder, odorless, stable in air and hygroscopic.
Estradiol USP is chemically described as estra-1,3,5(10)-triene-3, 17ß-diol. It has an empirical formula of C 18 H 24 O 2 and molecular weight of 272.38. The structural formula is: The Estradiol Transdermal System, USP comprises three layers.
Proceeding from the visible surface toward the surface attached to the skin, these layers are: A translucent polyethylene film. An acrylate adhesive matrix containing estradiol USP. A protective liner of silicone coated polyester film is attached to the adhesive surface and must be removed before the system can be used.
Cross Section of the System Estradiol Transdermal System, USP is packaged with additional pieces of protective film above and below the system within each pouch. These are discarded at the time of use. The active component of the system is estradiol USP.
The remaining components of the system (acrylic adhesive, colloidal silicon dioxide, ethyl oleate, glyceryl monolaurate, isopropyl myristate, povidone and polyethylene backing) are pharmacologically inactive. FDA approved drug release test specifications differ from USP. Estradiol Transdermal System Estradiol Transdermal System
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see 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. Manufactured by: Zydus Lifesciences Ltd. Ahmedabad, India Distributed by: Zydus Pharmaceuticals (USA) Inc.
Pennington, NJ 08534 Rev.: 03/24
💬 Medication Guide ▾
Patient Information Estradiol Transdermal System, USP (es" tra dye' ol) Rx only Read this Patient Information before you start using Estradiol Transdermal System 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 (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. 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 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.
What is Estradiol Transdermal System? Estradiol Transdermal System is a prescription medicine patch (transdermal system) that contains estradiol (an estrogen hormone). What is Estradiol Transdermal System used for?
The Estradiol Transdermal System 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 to control these problems. If you use Estradiol Transdermal System only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you. • Treat certain conditions in women before menopause if their ovaries do not produce enough estrogens naturally • Help reduce your chances of getting osteoporosis (thin weak bones) Osteoporosis from menopause is a thinning of the bones that makes them weaker and easier to break.
If you use Estradiol Transdermal System only to prevent osteoporosis due to me…