Hormone Patch And Vivia

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Hormone Patch Vivelle Dot
Hormone Patch And Weight Gain

Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding see Warnings and Precautions (5.2). Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4). 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 or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (14.4). In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens.

Used patches still contain estrogen. To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container. Best Cheaps🔥 ☀☀☀ buy estradiol patch ☀☀☀. Free pills with every order! Free shipping, quality, privacy, secure. Buy estradiol patch,Free Bonus Pills. When combined with the hormone progestin, the risks of breast cancer and heart attack may rise as well. The patch itself might irritate the skin where you apply it.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4). 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 or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (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). In the absence of comparable data, these risks should be assumed to be similar for other doses of CE plus MPA, and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Vivelle-Dot is an estrogen indicated for:. Treatment of moderate to severe vasomotor symptoms due to menopause.

Treatment 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 vaginal atrophy, topical vaginal products should be considered. Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. Prevention of postmenopausal osteoporosis Limitations of Use: When prescribing solely for the treatment of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered. Undiagnosed abnormal genital bleeding (, ). Known, suspected, or history of breast cancer (, ). Known or suspected estrogen-dependent neoplasia (, ). Active DVT, PE or a history of these conditions (, ).

Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions (, ). Known anaphylactic reaction or angioedema or hypersensitivity with Vivelle-Dot (, ). Known liver impairment or disease (, ). Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (, ).

Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin see Warnings and Precautions (5.2, 5.14). Use of estrogen-alone or in combination with a progestin, should be with the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be reevaluated periodically as clinically appropriate to determine whether treatment is still necessary. The adhesive side of Vivelle-Dot should be placed on a clean, dry area of the trunk of the body (including the abdomen or buttocks).

Vivelle-Dot should not be applied to the breasts. Vivelle-Dot should be replaced twice weekly. The sites of application must be rotated, with an interval of at least 1 week allowed between applications to a particular site. The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the system off. The system should be applied immediately after opening the pouch and removing the protective liner. The system should be pressed firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact, especially around the edges.

In the event that a system should fall off, the same system may be reapplied. If the same system cannot be reapplied, a new system should be applied to another location. In either case, the original treatment schedule should be continued. If a woman has forgotten to apply a patch, she should apply a new patch as soon as possible. The new patch should be applied on the original treatment schedule. The interruption of treatment in women taking Vivelle-Dot might increase the likelihood of breakthrough bleeding, spotting and recurrence of symptoms. 2.1 Moderate to Severe Vasomotor Symptoms 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. 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, treatment with Vivelle-Dot should be initiated 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week.

Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. Vivelle-Dot may be given continuously in patients who do not have an intact uterus. In those patients with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on drug followed by 1 week off drug). 2.2 Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy 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 the medication should be made 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 those patients with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on drug followed by 1 week off drug). 2.4 Prevention 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, treatment with Vivelle-Dot should be initiated 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 patients who do not have an intact uterus.

In those patients with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on drug followed by 1 week off drug). 5.1 Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.

Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year 1 and persisted see Clinical Studies (14.3). Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).

1 In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years) see Clinical Studies (14.3). The increase in risk was demonstrated after the first year and persisted. Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo 2 see Clinical Studies (14.3). Subgroup analyses of women 50 to 59 years of age suggest a statistically nonsignificant reduction in CHD events reported in women receiving daily CE (0.625 mg) –alone compared to placebo in women less than 10 years since menopause (8 versus 16 per 10,000 women-years). 1 In the WHI estrogen plus progestin substudy, there was a statistically nonsignificant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years).

1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 see Clinical Studies (14.3). 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 II, and overall.

Venous Thromboembolism In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE) was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years 3 see Clinical Studies (14.3). Should a VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated.

The increase in VTE risk was demonstrated during the first year and persisted 4 see Clinical Studies (14.3). Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.

If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. 5.2 Malignant Neoplasms Endometrial Cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus.

The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of estrogens for less than 1 year. The greatest risk appears to be associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE plus MPA compared with placebo. 6 Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for CE plus MPA compared with placebo. In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group.

Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. Ovarian Cancer The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer.

After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent CI, 0.77-3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years.

7 A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies.

The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval CI 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years median of 3 yearsvs. Greater than 5 years median of 10 years of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27-1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown. 5.3 Probable Dementia In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo. After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83 to 2.66).

The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). In the WHIMS estrogen plus progestin ancillary study of WHI, a population of 4,532 postmenopausal women 65 to 79 years was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21 to 3.48).

The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). When data from the 2 populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19 to 2.60). Since both ancillary studies were conducted in women aged 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). 5.7 Addition of a Progestin When a Woman Has Not Had a Hysterectomy Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens.

These include an increased risk of breast cancer. 5.11 Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.

5.15 Severe Anaphylactic/Anaphylactoid Reactions and Angioedema Cases of anaphylactic/anaphylactoid reactions, which developed anytime during the course of Vivelle-Dot treatment and required emergency medical management, have been reported in the postmarketing setting. Involvement of skin (hives, pruritus, swollen lips-tongue-face) and either respiratory tract (respiratory compromise) or gastrointestinal tract (abdominal pain, vomiting) has been noted. Angioedema involving eye/eyelid, face, larynx, pharynx, tongue and extremity (hands, legs, ankles, and fingers) with or without urticaria requiring medical intervention has occurred in the postmarketing experience of using Vivelle-Dot. If angioedema involves the tongue, glottis, or larynx, airway obstruction may occur. Patients who develop angioedema anytime during the course of treatment with Vivelle-Dot should not receive it again. Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema. 5.18 Drug-Laboratory Test Interactions.

Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex; and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III; decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone levels, as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay. T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone. Other binding proteins may be elevated in serum, for example, corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased.

Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma high-density lipoprotein (HDL) and HDL 2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglycerides levels. Impaired glucose tolerance. 6.2 Postmarketing 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 leiomyomata, vaginitis, vaginal discharge, ovarian cancer, endometrial hyperplasia, dysmenorrhea. Breast Enlargement, pain, nipple discharge, fibrocystic breast changes, breast cancer.

Other skin reactions include paresthesia, skin discoloration, skin pigmentation, urticaria, swelling, loss of scalp hair, hirsutism, pruritus, and rash. Eyes Intolerance to contact lenses. Central Nervous System Migraine, dizziness, chorea, nervousness, affect liability, irritability. Miscellaneous Decrease in weight, reduced carbohydrate tolerance, edema, arthralgias, leg cramps, changes in libido, purpura, hypersensitivity, anaphylactic reaction, anaphylactoid reaction, angioedema. 7.1 Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.

Inducers of CYP3A4 such as St. John’s wort ( Hypericum perforatum) preparations, phenobarbital, carbamazepine and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects. 8.4 Pediatric Use Estrogen therapy has been used for the induction of puberty in adolescents with some forms of pubertal delay. Safety and effectiveness in pediatric patients have not otherwise been established. Large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, which could result in short adult stature if treatment is initiated before the completion of physiologic puberty in normally developing children.

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 see Warnings and Precautions (5.3), and Clinical Studies (14.4).

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.

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

Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4). 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 or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (14.4). In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Hormone Patch Vivelle Dot

Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4). 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 or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women see Warnings and Precautions (5.3), Use in Specific Populations (8.5), and Clinical Studies (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).

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE plus MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Vivelle-Dot is an estrogen indicated for:.

Treatment of moderate to severe vasomotor symptoms due to menopause. Treatment 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 vaginal atrophy, topical vaginal products should be considered. Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. Prevention of postmenopausal osteoporosis Limitations of Use: When prescribing solely for the treatment of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered. Undiagnosed abnormal genital bleeding (, ). Known, suspected, or history of breast cancer (, ).

Known or suspected estrogen-dependent neoplasia (, ). Active DVT, PE or a history of these conditions (, ). Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions (, ). Known anaphylactic reaction or angioedema or hypersensitivity with Vivelle-Dot (, ). Known liver impairment or disease (, ).

Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (, ). Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin see Warnings and Precautions (5.2, 5.14). Use of estrogen-alone or in combination with a progestin, should be with the lowest effective dose and the shortest duration consistent with treatment goals and risks for the individual woman.

Postmenopausal women should be reevaluated periodically as clinically appropriate to determine whether treatment is still necessary. The adhesive side of Vivelle-Dot should be placed on a clean, dry area of the trunk of the body (including the abdomen or buttocks). Vivelle-Dot should not be applied to the breasts. Vivelle-Dot should be replaced twice weekly. The sites of application must be rotated, with an interval of at least 1 week allowed between applications to a particular site. The area selected should not be oily, damaged, or irritated.

The waistline should be avoided, since tight clothing may rub the system off. The system should be applied immediately after opening the pouch and removing the protective liner. The system should be pressed firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact, especially around the edges.

The new patch should be applied on the original treatment schedule. The interruption of treatment in women taking Vivelle-Dot might increase the likelihood of breakthrough bleeding, spotting and recurrence of symptoms. 2.1 Moderate to Severe Vasomotor Symptoms Start therapy with Vivelle-Dot 0.0375 mg per day applied to the skin twice weekly.

In women who are currently taking oral estrogens, treatment with Vivelle-Dot should be initiated 1 week after withdrawal of oral hormone therapy, or sooner if menopausal symptoms reappear in less than 1 week. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals. Vivelle-Dot may be given continuously in patients who do not have an intact uterus. In those patients with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on drug followed by 1 week off drug). 2.2 Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy 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 the medication should be made 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, treatment with Vivelle-Dot should be initiated 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 patients who do not have an intact uterus. In those patients with an intact uterus, Vivelle-Dot may be given on a cyclic schedule (for example, 3 weeks on drug followed by 1 week off drug). 5.1 Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy.

An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year 1 and persisted see Clinical Studies (14.3).

Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).

Hormone Patch And Weight Gain

Subgroup analyses of women 50 to 59 years of age suggest a statistically nonsignificant reduction in CHD events reported in women receiving daily CE (0.625 mg) –alone compared to placebo in women less than 10 years since menopause (8 versus 16 per 10,000 women-years). 1 In the WHI estrogen plus progestin substudy, there was a statistically nonsignificant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). 1 An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 see Clinical Studies (14.3). 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.

Descargar quien quiere ser millonario el juego para pc. 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 II, and overall. Venous Thromboembolism In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE) was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years).

The increase in VTE risk was demonstrated during the first 2 years 3 see Clinical Studies (14.3). Should a VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was demonstrated during the first year and persisted 4 see Clinical Studies (14.3). Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.

Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.

Breast Cancer The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the WHI substudy of daily CE (0.625 mg)-alone. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk RR 0.80) 5 see Clinical Studies (14.3). The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg).

After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE plus MPA compared with placebo. 6 Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for CE plus MPA compared with placebo. In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group.

Metastatic disease was rare, with no apparent difference between the 2 groups. Other prognostic factors, such as histologic subtype, grade, and hormone receptor status did not differ between the groups see Clinical Studies (14.3). Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation.

All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. Ovarian Cancer The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent CI, 0.77-3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years. 7 A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer.

The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval CI 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years median of 3 yearsvs. Greater than 5 years median of 10 years of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27-1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown. 5.3 Probable Dementia In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo.

After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83 to 2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). In the WHIMS estrogen plus progestin ancillary study of WHI, a population of 4,532 postmenopausal women 65 to 79 years was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia.

The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21 to 3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). When data from the 2 populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19 to 2.60).

Since both ancillary studies were conducted in women aged 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women 8 see Use in Specific Populations (8.5), and Clinical Studies (14.4). 5.7 Addition of a Progestin When a Woman Has Not Had a Hysterectomy Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer.

5.11 Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range. 5.15 Severe Anaphylactic/Anaphylactoid Reactions and Angioedema Cases of anaphylactic/anaphylactoid reactions, which developed anytime during the course of Vivelle-Dot treatment and required emergency medical management, have been reported in the postmarketing setting.

Involvement of skin (hives, pruritus, swollen lips-tongue-face) and either respiratory tract (respiratory compromise) or gastrointestinal tract (abdominal pain, vomiting) has been noted. Angioedema involving eye/eyelid, face, larynx, pharynx, tongue and extremity (hands, legs, ankles, and fingers) with or without urticaria requiring medical intervention has occurred in the postmarketing experience of using Vivelle-Dot.

If angioedema involves the tongue, glottis, or larynx, airway obstruction may occur. Patients who develop angioedema anytime during the course of treatment with Vivelle-Dot should not receive it again. Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema. 5.18 Drug-Laboratory Test Interactions. Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex; and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III; decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone levels, as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay.

T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone.

Other binding proteins may be elevated in serum, for example, corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

Increased plasma high-density lipoprotein (HDL) and HDL 2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentration, increased triglycerides levels. Impaired glucose tolerance. 6.2 Postmarketing 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 leiomyomata, vaginitis, vaginal discharge, ovarian cancer, endometrial hyperplasia, dysmenorrhea. Breast Enlargement, pain, nipple discharge, fibrocystic breast changes, breast cancer.

Cardiovascular Deep venous thrombosis, pulmonary embolism, thrombophlebitis. Gastrointestinal Nausea, vomiting, abdominal cramps, bloating, cholelithiasis, liver function tests abnormal, diarrhea. Skin Application site reactions include localized bleeding, bruising, burning, discomfort, dryness, eczema, edema, erythema, erythema multiforme, erythema nodosum, inflammation, irritation, pain, papules and vesicles. Other skin reactions include paresthesia, skin discoloration, skin pigmentation, urticaria, swelling, loss of scalp hair, hirsutism, pruritus, and rash. Eyes Intolerance to contact lenses. Central Nervous System Migraine, dizziness, chorea, nervousness, affect liability, irritability. Miscellaneous Decrease in weight, reduced carbohydrate tolerance, edema, arthralgias, leg cramps, changes in libido, purpura, hypersensitivity, anaphylactic reaction, anaphylactoid reaction, angioedema.

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

John’s wort ( Hypericum perforatum) preparations, phenobarbital, carbamazepine and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects. 8.4 Pediatric Use Estrogen therapy has been used for the induction of puberty in adolescents with some forms of pubertal delay. Safety and effectiveness in pediatric patients have not otherwise been established. Large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, which could result in short adult stature if treatment is initiated before the completion of physiologic puberty in normally developing children.

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. Estrogen treatment of prepubertal girls also induces premature breast development and vaginal cornification, and may induce vaginal bleeding. 8.5 Geriatric 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 see Warnings and Precautions (5.3), and Clinical Studies (14.4). 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.