Complete SPL Sections#
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER
BOXED WARNING SECTION
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 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 pulmonary embolism (PE), DVT, 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 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 ( 14.4 )] . 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
INDICATIONS & USAGE SECTION
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
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 with a history of endometriosis may need a progestogen [see Warnings and Precautions ( 5.2 , 5.14 )] . Use estrogen-alone, or in combination with a progestogen at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary.
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
EstroGel 0.06% is an estradiol transdermal gel. One pump depression delivers 1.25 g of gel that contains 0.75 mg estradiol.
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
EstroGel is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warning and Precautions ( 5.2 )] . Breast cancer or a history of breast cancer [see Warning and Precautions ( 5.2 )] . Estrogen-dependent neoplasia [see Warning and Precautions ( 5.2 )] . Active DVT, PE, or history of these conditions [see Warning and Precautions ( 5.1 )]. Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions [see Warning and Precautions ( 5.1 )] . Known anaphylactic reaction, angioedema, or hypersensitivity to EstroGel Hepatic impairment or disease Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , and Warnings and Precautions ( 5.1 )] Malignant Neoplasms [see Boxed Warning , and Warnings and Precautions ( 5.2 )]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
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 estrogen and may result in adverse reactions.
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
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 EstroGel therapy with institution of appropriate symptomatic care.
11 DESCRIPTION
DESCRIPTION SECTION
EstroGel (estradiol gel) contains 0.06 percent estradiol in an absorptive hydroalcoholic gel base for topical application. It is a clear, colorless gel, which is odorless when dry. One pump depression of EstroGel delivers 1.25 g of gel containing 0.75 mg estradiol. Estradiol is a white crystalline powder, chemically described as estra‑1,3,5(10)-triene-3,17β-diol. It has an empirical formula of C 18 H 24 O 2 and molecular weight of 272.39. The structural formula is: The active component of the gel is estradiol. The remaining components of the gel (purified water, alcohol, triethanolamine and carbomer 974P) are pharmacologically inactive.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
15 REFERENCES
REFERENCES SECTION
Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause. JAMA . 2007;297:1465-1477. Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med. 2006;166:357-365. Curb JD, et al. Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med. 2006;166:772-780. Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis. JAMA. 2004;292:1573-1580. Stefanick ML, et al. Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy. JAMA. 2006;295:1647-1657. Chlebowski RT, et al. Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA. 2003;289:3234-3253. Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures. JAMA. 2003;290:1739-1748. Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA. 2004;291:2947-2958. Jackson RD, et al. Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial. J Bone Miner Res. 2006;21:817-828. Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women's Health Initiative. Circulation. 2006;113:2425-2434.
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions ( 5.2 )] . Possible Serious Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of the possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . Possible Common Adverse Reactions with Estrogen-Alone Therapy Inform postmenopausal women of possible less serious but common adverse reactions of estrogen-alone therapy such as headache, breast pain and tenderness, nausea, and vomiting. Manufactured for: ASCEND Therapeutics ® US, LLC Bridgewater, NJ 08807 141367Rev052025 Utilizes EHG ® Technology ©2024 ASCEND Therapeutics ® US, LLC
Patient Information
SPL PATIENT PACKAGE INSERT SECTION
EstroGel ® 0.06% (ĕs’ trə jĕl) (estradiol gel) Read this Patient Information before you start using EstroGel, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment. What is the most important information I should know about EstroGel (an estrogen hormone)? Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Report any unusual vaginal bleeding right away while you are using EstroGel. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia (decline in brain function). Using estrogen-alone may increase your chances of getting strokes and blood clots. Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age and older. Do not use estrogens with progestogens to prevent heart disease, heart attack, strokes or dementia. Using estrogens with progestogens may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older. Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia. Because other products and doses have not been studied in the same way, it is not known how the use of EstroGel will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with EstroGel. What is EstroGel? EstroGel is a prescription medicine gel that contains estradiol (an estrogen hormone). What is EstroGel used for? EstroGel is used after menopause to: Reduce moderate to severe hot flashes Estrogens are hormones made by a woman’s ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the “change of life” or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes “surgical menopause.” When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating (“hot flashes” or “hot flushes”). In some women, the symptoms are mild, and they will not need to use estrogens. In other women, symptoms can be more severe. Treat moderate to severe menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with EstroGel to control these problems. If you use EstroGel only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you. Who should not use EstroGel? Do not start using EstroGel if you: have unusual vaginal bleeding Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. have been diagnosed with a bleeding disorder currently have or have had certain cancers Estrogen may increase the chance of getting certain types of cancer, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use EstroGel. had a stroke or heart attack currently have or have had blood clots currently have or have had liver problems are allergic to EstroGel or any of its ingredients See the list of ingredients in EstroGel at the end of this leaflet. Before you use EstroGel, tell your healthcare provider about all of your medical conditions, including if you: have any unusual vaginal bleeding Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause. have any other medical conditions that may become worse while you are using EstroGel Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, angioedema (swelling of face and tongue), problems with your heart, liver, thyroid, kidneys, or high calcium levels in your blood. are going to have surgery or will be on bed rest Your healthcare provider will let you know if you need to stop using EstroGel. are pregnant or think you may be pregnant EstroGel is not for pregnant women. are breastfeeding The hormone in EstroGel can pass into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how EstroGel works. EstroGel may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. How should I use EstroGel? For detailed instructions, see the step-by-step instructions for using EstroGel at the end of this Patient Information. Use EstroGel exactly as your healthcare provider tells you to use it. EstroGel is for skin use only. EstroGel contains alcohol, which is flammable. Avoid fire, flame or smoking until EstroGel has dried. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are using and whether you still need treatment with EstroGel. What are the possible side effects of EstroGel? Side effects are grouped by how serious they are and how often they happen when you are treated. Serious, but less common side effects include: heart attack stroke blood clots breast cancer cancer of the lining of the uterus (womb) cancer of the ovary dementia high or low blood calcium gallbladder disease worsening of swelling of face and tongue (angioedema) in women with a history of angioedema visual abnormalities high blood pressure high levels of fat (triglycerides) in your blood liver problems changes in your thyroid hormone levels fluid retention cancer changes of endometriosis enlargement of benign tumors of the uterus ("fibroids") changes in laboratory test results such as bleeding time and high blood sugar Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you: new breast lumps unusual vaginal bleeding changes in vision or speech sudden new severe headaches severe pains in your chest or legs with or without shortness of breath, weakness and fatigue swelling of face, lips, and tongue with or without red, itchy bumps Common side effects of EstroGel include: headache breast tenderness or pain stomach or abdominal cramps, bloating nausea and vomiting hair loss fluid retention vaginal yeast infection These are not all of the possible side effects of EstroGel. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or do not go away. You may report side effects to FDA at 1-800-FDA 1088 or to ASCEND Therapeutics ® US, LLC at 1‑877-204-1013. What can I do to lower my chances of a serious side effect with EstroGel? Talk with your healthcare provider regularly about whether you should continue using EstroGel. If you have a uterus, talk with your healthcare provider about whether the addition of a progestogen is right for y...
PRINCIPAL DISPLAY PANEL - EstroGel 50g
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 17139-617-40 ESTROGel ® 0.06% (estradiol gel) 0.75 mg of estradiol per pump actuation* *Each actuation delivers 1.25 g of gel For Topical Use Only. A multi-dose pump capable of dispensing 30 metered pump actuations. Rx only
PRINCIPAL DISPLAY PANEL - EstroGel 50g
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 17139-617-40 ESTROGel ® 0.06% (estradiol gel) 0.75 mg of estradiol per pump actuation* *Each actuation delivers 1.25 g of gel For Topical Use Only. A multi-dose pump capable of dispensing 30 metered pump actuations. Rx only
