Vivelle-Dot estradiol .0375 mg/d Patch, Extended Release, 8 patches
Other active recalls for Estradiol (different manufacturers) — 4 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Radioactive Diagnostic Agent class.
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🏭 Manufacturer & labeler
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🩺 Clinical
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.
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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.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.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 ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $18.376 | $147.01 / 8 patch |
| Medicaid paysCMS SDUD · 12 mo | $18.12 | $144.99 / 8 patch |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Estradiol .0375 mg/d 00378-4620-26 | Mylan | 8 patches | $8.262 | AB3 | Availability likely | save 55% |
| Estradiol .0375 mg/d 00378-4643-26 | Mylan | 8 patches | $8.262 | AB1 | Availability likely | save 55% |
| Lyllana .0375 mg/d 65162-0148-08 | Amneal | 8 pouches | $8.262 | AB3 | Availability likely | save 55% |
| Dotti .0375 mg/d 65162-0992-08 | Amneal | 8 pouches | $8.262 | AB1 | Availability likely | save 55% |
| Estradiol .0375 mg/d 68968-3437-08 | Noven | 8 pouches | $8.262 | AB3 | Availability likely | save 55% |
| Estradiol .0375 mg/d 70710-1192-08 | Zydus | 8 patches | $8.262 | AB1 | Availability likely | save 55% |
| Minivelle .0375 mg/d 68968-6637-08 | Noven | 8 pouches | $11.584 | AB3 | Availability likely | save 37% |
| Estradiol .0375 mg/d 00378-3360-99 | Mylan | 4 patches | $11.930 | AB2 | Availability likely | save 35% |
| Estradiol Transdermal System .0375 mg/d 00781-7122-54 | Sandoz | 4 patches | $11.930 | AB2 | Availability likely | save 35% |
| Climara .0375 mg/d 50419-0456-04 | Bayer | 4 patches | $18.298 | AB2 | Availability likely | +0% |
| Vivelle-Dot .0375 mg/dthis 66758-0146-83 | Sandoz | 8 patches | $18.376 | AB1 | Availability likely | — |
| Estradiol .0375 mg/d 00781-7138-40 | Sandoz | 24 patches | — | AB1 | Discontinued | — |
| Estradiol .0375 mg/d 50090-7610-00 | A-S | 8 pouches | — | AB3 | FDA listed | — |
| Estradiol .0375 mg/d 69238-1293-07 | Amneal | 8 pouches | — | AB3 | FDA listed | — |
| Estradiol .0375 mg/d 69238-1630-07 | Amneal | 8 pouches | — | AB1 | FDA listed | — |
| Estradiol .0375 mg/d 70771-1564-08 | Zydus | 8 patches | — | AB1 | FDA listed | — |
| Dotti .0375 mg/d 72162-2033-02 | Bryant | 8 pouches | — | AB1 | FDA listed | — |
| estradiol .0375 mg/d 70771-1402-04 | Zydus | 4 patches | — | AB2 | FDA listed | — |
| estradiol .0375 mg/d 68382-0325-04 | Zydus | 4 patches | — | AB2 | FDA listed | — |
| Estradiol .0375 mg/d 50090-7987-00 | A-S | 4 pouches | — | AB2 | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 66758-0146-83 You're viewing this | 8 POUCH in 1 BOX (66758-146-83) / 1 PATCH in 1 POUCH (66758-146-58) / 3.5 d in 1 PATCH | 2024-06-10 | Active |
📄 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 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 progesto…
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Vivelle-Dot is indicated for: Vivelle-Dot 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 vaginal atrophy, 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.
1.1Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause .
1.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy Due to Menopause Limitations of Use : When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, 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 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.
⏱️ 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 the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. • Start therapy with Vivelle-Dot 0.0375 mg/day applied to the skin twice weekly for the treatment of moderate to severe vasomotor symptoms due to menopause or moderate to severe symptoms of vulvar and vaginal atrophy symptoms due to menopause.
Dosage adjustment should be guided by the clinical response ( 2.1 , 2.2 , 2.3 ) • Start therapy with Vivelle-Dot 0.025 mg/day for the prevention of postmenopausal osteoporosis ( 2.4 ) • Place Vivelle-Dot on a clean, dry area of the lower abdomen or buttocks. Do not apply Vivelle-Dot to the breasts ( 2.5 )
2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with Vivelle-Dot 0.0375 mg per day applied to the skin twice weekly. Make dosage adjustments based on the clinical response. Initiate Vivelle-Dot at once in a woman not currently taking oral estrogens or in a woman switching from another estradiol transdermal therapy.
In women who are currently taking oral estrogens, initiate treatment with Vivelle-Dot 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Attempts to taper or discontinue Vivelle-Dot at 3 to 6-month intervals. Give Vivelle-Dot continuously in a woman who does not have an intact uterus.
In a woman with an intact uterus, give Vivelle-Dot on a cyclic schedule (for example, 3 weeks on Vivelle-Dot followed by 1 week off Vivelle-Dot).
2.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Start therapy with Vivelle-Dot 0.0375 mg per day applied to the skin twice weekly. Dosage adjustment should be guided by the clinical response. Attempts to taper or discontinue Vivelle-Dot at 3 to 6-month intervals.
In women not currently taking oral estrogens or in women switching from another estradiol transdermal therapy, treatment with Vivelle-Dot may be initiated at once. In women who are currently taking oral estrogens, initiate treatment with Vivelle-Dot 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Give Vivelle-Dot continuously in a woman who does not have an intact uterus.
In a woman with an intact uterus, give Vivelle-Dot on a cyclic schedule (for example, 3 weeks on Vivelle-Dot followed by 1 week off Vivelle-Dot).
2.3Hypoestrogenism Due to Hypogonadism, Castration, or Primary Ovarian Failure .
2.4Prevention of Postmenopausal Osteoporosis Start therapy with Vivelle-Dot 0.025 mg per day applied to the skin twice weekly. In women not currently taking oral estrogens or in women switching from another estradiol transdermal therapy, treatment with Vivelle-Dot may be initiated at once. In women who are currently taking oral estrogens, initiate treatment with Vivelle-Dot 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week.
Vivelle-Dot may be given continuously in a woman who does not have an intact uterus. In a woman with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on Vivelle-Dot followed by 1 week off Vivelle-Dot).
2.5Application Instructions Place the adhesive side of Vivelle-Dot on a clean, dry area of the trunk of the body (including the abdomen or buttocks). D…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Transdermal system: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, and 0.1 mg/day. Transdermal system: 0.025 mg/day, 0.0375 mg/day, 0.05 mg/day, 0.075 mg/day, and 0.1 mg/day ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Vivelle-Dot is contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2)] . • Breast cancer or a 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 and MI), or a history of these conditions [see Warnings and Precautions (5.1)] . • Known anaphylactic reaction, or angioedema, or hypersensitivity to Vivelle-Dot • 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 and MI), or a history of these conditions ( 4 , 5.1 ) • Known anaphylactic reaction, or angioedema, or hypersensitivity with Vivelle-Dot ( 4 , 5.15 ) • 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 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 CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 stokes per 10,000 women-years) [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) in 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) in 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 group in the HERS, the HERS I…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in labeling: • Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions (5.1)] • Malignant Neoplasms [see Boxed Warning, Warnings and Precautions (5.2)] The most common adverse reactions (≥ 10%) with Vivelle-Dot are: headache, breast tenderness, nasopharyngitis, sinusitis, sinus headache, upper respiratory tract infection, back pain, depression, and irregular vaginal bleeding or spotting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 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. There were no clinical trials conducted with Vivelle-Dot. Vivelle-Dot is bioequivalent to Vivelle ® .
The following adverse reactions have been reported with Vivelle therapy: Table 1. Summary of Most Frequently Reported Adverse Reactions Regardless of Relationship Reported at a Frequency ≥ 5 Percent † Represents milligrams of estradiol delivered daily by each system. * NOS represents not otherwise specified. ** NEC represents not elsewhere classified. *** Application site erythema and application site irritation were observed in a small number of patients (3.2% or less of patients across treatment groups). Vivelle 0.025 mg/day † (N = 47) N (%) Vivelle 0.0375 mg/day † (N = 130) N (%) Vivelle 0.05 mg/day † (N = 103) N (%) Vivelle 0.075 mg/day † (N = 46) N (%) Vivelle 0.1 mg/day † (N = 132) N (%) Placebo (N = 157) N (%) Gastrointestinal disorders Constipation 2 (4.3) 5 (3.8) 4 (3.9) 3 (6.5) 2 (1.5) 4 (2.5) Dyspepsia 4 (8.5) 12 (9.2) 3 (2.9) 2 (4.3) 0 10 (6.4) Nausea 2 (4.3) 8 (6.2) 4 (3.9) 0 7 (5.3) 5 (3.2) General disorders and administration site conditions *** Influenza-like illness 3 (6.4) 6 (4.6) 8 (7.8) 0 3 (2.3) 10 (6.4) Pain NOS * 0 8 (6.2) 0 2 (4.3) 7 (5.3) 7 (4.5) Infections and infestations Influenza 4 (8.5) 4 (3.1) 6 (5.8) 0 10 (7.6) 14 (8.9) Nasopharyngitis 3 (6.4) 16 (12.3) 10 (9.7) 9 (19.6) 11 (8.3) 24 (15.3) Sinusitis NOS * 4 (8.5) 17 (13.1) 13 (12.6) 3 (6.5) 7 (5.3) 16 (10.2) Upper respiratory tract infection NOS * 3 (6.4) 8 (6.2) 11 (10.7) 4 (8.7) 6 (4.5) 9 (5.7) Investigations Weight increased 4 (8.5) 5 (3.8) 2 (1.9) 2 (4.3) 0 3 (1.9) Musculoskeletal and connective tissue disorders Arthralgia 0 11 (8.5) 4 (3.9) 2 (4.3) 5 (3.8) 9 (5.7) Back pain 4 (8.5) 10 (7.7) 9 (8.7) 4 (8.7) 14 (10.6) 10 (6.4) Neck pain 3 (6.4) 4 (3.1) 4 (3.9) 0 6 (4.5) 2 (1.3) Pain in limb 0 10 (7.7) 7 (6.8) 2 (4.3) 6 (4.5) 9 (5.7) Nervous system disorders Headache NOS * 7 (14.9) 35 (26.9) 32 (31.1) 23 (50.0) 34 (25.8) 37 (23.6) Sinus headache 0 12 (9.2) 5 (4.9) 5 (10.9) 2 (1.5) 8 (5.1) Psychiatric disorders Anxiety NEC ** 3 (6.4) 5 (3.8) 0 0 2 (1.5) 4 (2.5) Depression 5 (10.6) 4 (3.1) 7 (6.8) 0 4 (3.0) 6 (3.8) Insomnia 3 (6.4) 6 (4.6) 4 (3.9) 2 (4.3) 2 (1.5) 9 (5.7) Reproductive system and breast disorders Breast tenderness 8 (17.0) 10 (7.7) 8 (7.8) 3 (6.5) 17 (12.9) 0 Dysmenorrhea 0 0 0 3 (6.5) 0 0 Intermenstrual bleeding 3 (6.4) 9 (6.9) 6 (5.8) 0 14 (10.6) 7 (4.5) Respiratory, thoracic and mediastinal disorders Sinus congestion 0 4 (3.1) 3 (2.9) 3 (6.5) 6 (4.5) 7 (4.5) Vascular disorders Hot flushes NOS * 3 (6.4) 0 3 (2.9) 0 0 6 (3.8) Hypertension NOS * 2 (4.3) 0 3 (2.9) 0 0 2 (1.3)
6.2Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of Vivelle-Dot. 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 Vaginal hemorrhage and abnormal withdrawal bleeding or flow, breakthrough bleeding, spotting, uterine lei…
🔄 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 Vivelle-Dot is not indicated for use in pregnancy. There are no data with the use of Vivelle-Dot 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 (estrogen 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 Vivelle-Dot and any potential adverse effects on the breastfed child from Vivelle-Dot or from the underlying maternal condition.
8.4Pediatric Use Vivelle-Dot 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 maturation 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 Vivelle-Dot to determine whether those over 65 years of age differ from younger subjects in their response to Vivelle-Dot. 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 Warnings and Precautions (5.1), and 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 Warnings and Precautions (5.1), and 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 Vivelle-Dot is not indicated for use in pregnancy. There are no data with the use of Vivelle-Dot 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 (estrogen 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 Vivelle-Dot 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 maturation 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 Vivelle-Dot to determine whether those over 65 years of age differ from younger subjects in their response to Vivelle-Dot. 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 Warnings and Precautions (5.1), and 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 Warnings and Precautions (5.1), and 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 may occur in women. Treatment of overdose consists of discontinuation of Vivelle-Dot therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, 2 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 follicle stimulating hormone (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 Vivelle-Dot 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 In a multiple-dose study consisting of 3 consecutive system applications of the original formulation [Vivelle (estradiol transdermal system)] which was conducted in 17 healthy, postmenopausal women, blood levels of estradiol and estrone were compared following application of these units to sites on the abdomen and buttocks in a crossover fashion. Systems that deliver nominal estradiol doses of approximately 0.0375 mg per day and 0.1 mg per day were applied to abdominal application sites while the 0.1 mg per day doses were also applied to sites on the buttocks.
These systems increased estradiol levels above baseline within 4 hours and maintained respective mean levels of 25 and 79 pg/mL above baseline following application to the abdomen; slightly higher mean levels of 88 pg/mL above baseline were observed following application to the buttocks. At the same time, increases in estrone plasma concentrations averaged about 12 and 50 pg/mL, respectively, following application to the abdomen and 61 pg/mL for the buttocks. While plasma concentrations of estradiol and estrone remained slightly above baseline at 12 hours following removal of the systems in this study, results from another study show these levels to return to baseline values within 24 hours following removal of the systems.
Figure 1 illustrates the mean plasma concentrations of estradiol at steady-state during application of these patches at 4 different dosages. Figure 1. Steady-State Estradiol Plasma Concentrations for Systems Applied to the Abdomen Nonbaseline-corrected Levels The corresponding pharmacokinetic parameters are summarized in Table 2.
Table 2. Steady-State Estradiol Pharmacokinetic Parameters for Systems Applied to the Abdomen (mean ± standard deviation) Nonbaseline-corrected Data* * Mean baseline estradiol concentration =11.7 pg/mL. † Peak plasma concentration. ‡ Average plasma concentration. § Minimum plasma concentration at 84 hr. # Measured over 80 hr. ¶ Applied to the buttocks. Dosage (mg/day) C max † (pg/mL) C avg ‡ (pg/mL) C min (84 hr) § (pg/mL) 0.0375 46 ± 16 34 ± 10 30 ±10 0.05 83 ± 41 57 ± 23 # 41 ± 11 # 0.075 99 ± 35 72 ± 24 60 ± 24 0.1 133 ± 51 89 ± 38 90 ± 44 0.1 ¶ 145 ± 71 104 ± 52 85 ± 47 Vivelle-Dot (estradiol transdermal system), the revised formu…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, 2 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 follicle stimulating hormone (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 Vivelle-Dot (estradiol transdermal system), 0.025 mg per day -each 2.5 cm 2 system contains 0.39 mg of estradiol USP for nominal* delivery of 0.025 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-145-83 Vivelle-Dot (estradiol transdermal system), 0.0375 mg per day -each 3.75 cm 2 system contains 0.585 mg of estradiol USP for nominal* delivery of 0.0375 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-146-83 Vivelle-Dot (estradiol transdermal system), 0.05 mg per day -each 5.0 cm 2 system contains 0.78 mg of estradiol USP for nominal* delivery of 0.05 mg of estradiol per day.
Patient Calendar Pack of 8 Systems………………………………………NDC 66758-147-83 Vivelle-Dot (estradiol transdermal system), 0.075 mg per day -each 7.5 cm 2 system contains 1.17 mg of estradiol USP for nominal* delivery of 0.075 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-148-83 Vivelle-Dot (estradiol transdermal system), 0.1 mg per day -each 10.0 cm 2 system contains 1.56 mg of estradiol USP for nominal* delivery of 0.1 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-149-83 [*see DESCRIPTION (11)]
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Do not store unpouched. 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 Vivelle-Dot (estradiol transdermal system), 0.025 mg per day -each 2.5 cm 2 system contains 0.39 mg of estradiol USP for nominal* delivery of 0.025 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-145-83 Vivelle-Dot (estradiol transdermal system), 0.0375 mg per day -each 3.75 cm 2 system contains 0.585 mg of estradiol USP for nominal* delivery of 0.0375 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-146-83 Vivelle-Dot (estradiol transdermal system), 0.05 mg per day -each 5.0 cm 2 system contains 0.78 mg of estradiol USP for nominal* delivery of 0.05 mg of estradiol per day.
Patient Calendar Pack of 8 Systems………………………………………NDC 66758-147-83 Vivelle-Dot (estradiol transdermal system), 0.075 mg per day -each 7.5 cm 2 system contains 1.17 mg of estradiol USP for nominal* delivery of 0.075 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-148-83 Vivelle-Dot (estradiol transdermal system), 0.1 mg per day -each 10.0 cm 2 system contains 1.56 mg of estradiol USP for nominal* delivery of 0.1 mg of estradiol per day. Patient Calendar Pack of 8 Systems………………………………………NDC 66758-149-83 [*see DESCRIPTION (11)]
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Do not store unpouched. 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 Vivelle-Dot (estradiol transdermal system) contains estradiol in a multipolymeric adhesive. The system is designed to release estradiol continuously upon application to intact skin. Five dosage strengths of Vivelle-Dot are available to provide nominal in vivo delivery rates of 0.025, 0.0375, 0.05, 0.075, or 0.1 mg of estradiol per day via the skin.
Each corresponding system has an active surface area of 2.5, 3.75, 5.0, 7.5, or 10.0 cm 2 and contains 0.39, 0.585, 0.78, 1.17, or 1.56 mg of estradiol USP, respectively. The composition of the systems per unit area is identical. Estradiol USP is a white, crystalline powder, chemically described as estra-1,3,5 (10)- triene-3,17β-diol.
The structural formula is: The molecular formula of estradiol is C 18 H 24 0 2 . The molecular weight is 272.39 g/mol. Vivelle-Dot is comprised of 3 layers.
Proceeding from the visible surface toward the surface attached to the skin, these layers are (1) a translucent polyolefin film (2) an adhesive formulation containing estradiol, acrylic adhesive, silicone adhesive, oleyl alcohol, NF, povidone, USP and dipropylene glycol, and (3) a polyester release liner which is attached to the adhesive surface and must be removed before the system can be used. ----- (1) Backing ----- (2) Adhesive Containing Estradiol ----- (3) Protective Liner The active component of the system is estradiol.
The remaining components of the system are pharmacologically inactive. estradiolstructuralformula vivelledotlayerimage
💬 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 providers as soon as possible [see Warnings 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.