Estradiol
ESTRADIOL- estradiol film, extended release
Noven Therapeutics, LLC
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 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 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)].
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4].
Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other route 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 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)].
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3), and Clinical Studies (14.3, 14.4)].
Breast Cancer
The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.2), and Clinical Studies (14.3)].
Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen 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 plus progestogen 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.
1 INDICATIONS AND USAGE
1.1 Treatment of Moderate to Severe Vasomotor Symptoms Due to Menopause
1.2 Prevention of Postmenopausal Osteoporosis
Limitation of UseWhen 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.
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 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 of estrogen-alone, or in combination with a progestogen, at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary.
2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause
Start therapy with ESTRADIOL TRANSDERMAL SYSTEM 0.0375 mg per day applied to the skin twice weekly. Make dosage adjustments based on clinical response.
Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication at 3 to 6 month intervals.
2.2 Prevention of Postmenopausal Osteoporosis due to Menopause
2.3 Application Instructions
Place the adhesive side of ESTRADIOL TRANSDERMAL SYSTEM on a clean, dry area on the lower abdomen (below the umbilicus) or buttocks. Do not apply ESTRADIOL TRANSDERMAL SYSTEM to the breasts.
Replace ESTRADIOL TRANSDERMAL SYSTEM twice weekly (every 3-4 days).
Rotate the sites of application, with an interval of at least 1 week allowed between applications to a particular site.
Select an area for application that is not oily, damaged, or irritated. Avoid the waistline, since tight clothing may rub the system off. Apply the system immediately after opening the pouch and removing the protective liner. Press the system firmly in place with the palm of the hand for about 10 seconds, making sure there is good contact with the skin, especially around the edges. In the event that a system falls off, reapply the same system or apply a new system to another location. If a woman has forgotten to apply ESTRADIOL TRANSDERMAL SYSTEM, have her apply a new system as soon as possible. Apply the new system on the original treatment schedule. The interruption of treatment in women taking ESTRADIOL TRANSDERMAL SYSTEM might increase the likelihood of breakthrough bleeding, spotting and recurrence of symptoms.
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.
4 CONTRAINDICATIONS
ESTRADIOL TRANSDERMAL SYSTEM is contraindicated in women with any of the following conditions:
- Undiagnosed abnormal genital bleeding [See Warnings and Precautions (5.2)].
- Breast cancer or 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 or MI), or a history of these conditions [See Warnings and Precautions (5.2)].
- Known anaphylactic reaction or angioedema or hypersensitivity to ESTRADIOL TRANSDERMAL SYSTEM
- Hepatic impairment or disease
- Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
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