Save up to 80% by drug discount in your pharmacy with "Pharmacy Near Me - National Drug Discount Card"
You can scan QR Code(just open camera on your phone/scan by application) from the image on prescription drug discount card to save it to your mobile phone. Or just click on image if you're on mobile phone.
| Product NDC Code | 17139-617 | ||||
|---|---|---|---|---|---|
| Drug Name | Estrogel |
||||
| Type | Brand | ||||
| Pharm Class | Estradiol Congeners [CS], Estrogen Receptor Agonists [MoA], Estrogen [EPC] |
||||
| Active Ingredients |
|
||||
| Route | TOPICAL | ||||
| Dosage Form | GEL, METERED | ||||
| RxCUI drug identifier | 226597, 581549 |
||||
| Application Number | NDA021166 | ||||
| Labeler Name | ASCEND Therapeutics US, LLC | ||||
| Packages |
|
||||
| Check if available Online | Get Medication Prices online with Discount |
Overdosage of EstroGel
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.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 EstroGel therapy with institution of appropriate symptomatic care.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , and Warnings and Precautions ( 5.1 )] Malignant Neoplasms [see Boxed Warning , and Warnings and Precautions ( 5.2 )] The most common adverse reactions with EstroGel (≥5 percent) are: headache, flatulence, and breast pain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ASCEND Therapeutics® US, LLC at 1-877-204-1013 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 clinical practice. EstroGel was studied in 2 well-controlled, 12-week clinical trials. Incidence of adverse drug reactions ≥5 percent for 1.25 g EstroGel 0.06% and placebo is given in Table 1 . Table 1 Incidence of Adverse Drug Reactions ≥5 Percent Occurrence in the EstroGel Treatment Group for the Intent-to-Treat Safety Population in 2 Well-controlled Clinical Studies (Expressed as Percent of Treatment Group) Body System/ Adverse Drug Reactions EstroGel 0.06% 1.25 g /day (n=168) Placebo (n=73) BODY AS A WHOLE Headache 9.5 2.7 DIGESTIVE SYSTEM Flatulence 5.4 4.1 UROGENITAL SYSTEM Breast pain 10.7 8.2 In 2 controlled clinical trials, application site reactions were reported by 0.6 percent of patients who received 1.25 g of EstroGel. Other skin reactions, such as pruritus and rash, were also noted. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of EstroGel. 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 Endometrial cancer Breast Pain; tenderness; breast cancer Cardiovascular Deep vein thrombosis; myocardial ischemia; phlebitis Gastrointestinal Nausea; abdominal distension; diarrhea; stomach discomfort Skin Alopecia; rash; pruritus; application site: dryness, pain, discoloration, reaction, rash Eyes Retinal vein occlusion Central nervous system Headache; dizziness; insomnia; hypoesthesia; meningioma; aphasia; bradyphrenia; paresthesia Miscellaneous Drug ineffective; hot flush; arthralgia; night sweats; drug effect decreased; pain in extremity; fatigue; weight increased; pain; hypersensitivity; dyspnea; malignant mesenchymoma; angioedema; hepatitis acute; face edema; accidental exposure; myoclonus; gait disturbance; flushing
EstroGel Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. ( 7.1 ) 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 reaction.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism 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 FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. 12.2 Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to EstroGel 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. 12.3 Pharmacokinetics Absorption Estradiol is transported across intact skin and into the systemic circulation by a passive diffusion process. The rate of diffusion across the stratum corneum is the rate-limiting factor. When EstroGel is applied to the skin, it dries in 2 to 5 minutes. EstroGel 1.25 g (containing 0.75 mg of estradiol) was administered to 24 postmenopausal women once daily on the posterior surface of 1 arm from wrist to shoulder for 14 consecutive days. Mean maximal serum concentrations of estradiol and estrone on Day 14 were 46.4 pg/mL and 64.2 pg/mL, respectively. The time‑averaged serum estradiol and estrone concentrations over the 24-hour dose interval after administration of 1.25 g EstroGel on Day 14 are 28.3 pg/mL and 48.6 pg/mL, respectively. Mean concentration-time profiles for unadjusted estradiol and estrone on Day 14 are shown in Figure 1 . FIGURE 1 Mean Serum Concentration-time Profiles for Unadjusted Estradiol and Estrone After Multiple-dose Applications of 1.25 g EstroGel 0.06% for 14 Days The serum concentrations of estradiol following 2.5 g EstroGel applications (1.25 g on each arm from wrist to shoulder) appeared to reach steady state after the third daily application. Distribution The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in blood largely bound to SHBG and albumin. Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is a major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. Although the clinical significance has not been determined, estradiol from EstroGel does not go through first‑pass liver metabolism. Excretion Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates. The apparent terminal exponential half-life for estradiol was about 36 hours following administration of 1.25 g EstroGel. Effect of Application Site Washing The effect of application site washing on the serum concentrations of estradiol was determined in 24 healthy postmenopausal women who applied 1.25 g of EstroGel once daily for 14 consecutive days. Site washing 1 hour after the application resulted in a 22 percent mean decrease in average 24-hour serum concentrations of estradiol. Potential for Estradiol Transfer The effect of estradiol transfer was evaluated in 24 healthy postmenopausal women who topically applied 1.25 g of EstroGel once daily on the posterior surface of 1 arm from wrist to shoulder for a period of 14 consecutive days. On each day, 1 hour after gel application, a cohort of 24 non-dosed healthy postmenopausal females directly contacted the dosed cohort at the site of gel application for 15 minutes. No change in endogenous mean serum concentrations of estradiol was observed in the non-dosed cohort after direct skin-to-skin contact with subjects administered EstroGel. Effect of Moisturizer Lotion/Sunscreen on Estradiol Absorption The effect of sunscreen and moisturizer lotion on estradiol absorption from 0.06% estradiol topical gel was evaluated in a randomized, open-label, three-period crossover study in 42 healthy postmenopausal women. The study results showed that repeated daily application of sunscreen for 7 days at 1 hour after the administration of 0.06% estradiol topical gel decreased the mean AUC 0-24h and C max of estradiol by 16%. Repeated daily application of moisturizer lotion for 7 days at 1 hour after the administration of 0.06% estradiol topical gel increased the mean AUC 0-24h and C max of estradiol by 38% and 73%, respectively. The effect of daily application of sunscreen/moisturizer lotion on estradiol absorption, when sunscreen/moisturizer lotion is applied before administration of 0.06% estradiol topical gel, was not studied. Figure 1 Mean Serum Concentration-time Profiles for Unadjusted Estradiol and Estrone After Multiple-dose Applications of 1.25 g EstroGel 0.06% for 14 Days
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism 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 FSH through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Generally, a serum estrogen concentration does not predict an individual woman’s therapeutic response to EstroGel 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.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Absorption Estradiol is transported across intact skin and into the systemic circulation by a passive diffusion process. The rate of diffusion across the stratum corneum is the rate-limiting factor. When EstroGel is applied to the skin, it dries in 2 to 5 minutes. EstroGel 1.25 g (containing 0.75 mg of estradiol) was administered to 24 postmenopausal women once daily on the posterior surface of 1 arm from wrist to shoulder for 14 consecutive days. Mean maximal serum concentrations of estradiol and estrone on Day 14 were 46.4 pg/mL and 64.2 pg/mL, respectively. The time‑averaged serum estradiol and estrone concentrations over the 24-hour dose interval after administration of 1.25 g EstroGel on Day 14 are 28.3 pg/mL and 48.6 pg/mL, respectively. Mean concentration-time profiles for unadjusted estradiol and estrone on Day 14 are shown in Figure 1 . FIGURE 1 Mean Serum Concentration-time Profiles for Unadjusted Estradiol and Estrone After Multiple-dose Applications of 1.25 g EstroGel 0.06% for 14 Days The serum concentrations of estradiol following 2.5 g EstroGel applications (1.25 g on each arm from wrist to shoulder) appeared to reach steady state after the third daily application. Distribution The distribution of exogenous estrogens is similar to that of endogenous estrogens. Estrogens are widely distributed in the body and are generally found in higher concentrations in the sex hormone target organs. Estrogens circulate in blood largely bound to SHBG and albumin. Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is a major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the intestine followed by reabsorption. In postmenopausal women, a significant proportion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. Although the clinical significance has not been determined, estradiol from EstroGel does not go through first‑pass liver metabolism. Excretion Estradiol, estrone, and estriol are excreted in the urine along with glucuronide and sulfate conjugates. The apparent terminal exponential half-life for estradiol was about 36 hours following administration of 1.25 g EstroGel. Effect of Application Site Washing The effect of application site washing on the serum concentrations of estradiol was determined in 24 healthy postmenopausal women who applied 1.25 g of EstroGel once daily for 14 consecutive days. Site washing 1 hour after the application resulted in a 22 percent mean decrease in average 24-hour serum concentrations of estradiol. Potential for Estradiol Transfer The effect of estradiol transfer was evaluated in 24 healthy postmenopausal women who topically applied 1.25 g of EstroGel once daily on the posterior surface of 1 arm from wrist to shoulder for a period of 14 consecutive days. On each day, 1 hour after gel application, a cohort of 24 non-dosed healthy postmenopausal females directly contacted the dosed cohort at the site of gel application for 15 minutes. No change in endogenous mean serum concentrations of estradiol was observed in the non-dosed cohort after direct skin-to-skin contact with subjects administered EstroGel. Effect of Moisturizer Lotion/Sunscreen on Estradiol Absorption The effect of sunscreen and moisturizer lotion on estradiol absorption from 0.06% estradiol topical gel was evaluated in a randomized, open-label, three-period crossover study in 42 healthy postmenopausal women. The study results showed that repeated daily application of sunscreen for 7 days at 1 hour after the administration of 0.06% estradiol topical gel decreased the mean AUC 0-24h and C max of estradiol by 16%. Repeated daily application of moisturizer lotion for 7 days at 1 hour after the administration of 0.06% estradiol topical gel increased the mean AUC 0-24h and C max of estradiol by 38% and 73%, respectively. The effect of daily application of sunscreen/moisturizer lotion on estradiol absorption, when sunscreen/moisturizer lotion is applied before administration of 0.06% estradiol topical gel, was not studied. Figure 1 Mean Serum Concentration-time Profiles for Unadjusted Estradiol and Estrone After Multiple-dose Applications of 1.25 g EstroGel 0.06% for 14 Days
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS 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 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 history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions ( 4 , 5.1 ) Known anaphylactic reaction, angioedema, or hypersensitivity to EstroGel ( 4 ) Hepatic impairment or disease ( 4 , 5.10 ) Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION 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 934P) are pharmacologically inactive. Estradiol Structural Formula
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.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 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. Metered-dose pump: Daily administration of EstroGel 0.06% 1.25 g per day (1 pump depression) to the arm ( 2.1 , 2.2 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause EstroGel 0.06% 1.25 g per day is the single approved dose for the treatment of moderate to severe vasomotor symptoms due to menopause. The lowest effective dose of EstroGel 0.06% for this indication has not been determined. Before using the canister for the first time, it must be primed. Remove the large canister cover, and fully depress the pump 5 times. Discard the unused gel by thoroughly rinsing down the sink or placing it in the household trash. After priming, the pump is ready to use. The recommended area of application is the arm. Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder. 2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause EstroGel 0.06% 1.25 g per day is the single approved dose for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. The lowest effective dose of EstroGel 0.06% for this indication has not been determined. When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy, first consider the use of topical vaginal products. Before using the canister for the first time, it must be primed. Remove the large canister cover, and fully depress the pump 5 times. Discard the unused gel by thoroughly rinsing down the sink or placing it in the household trash. After priming, the pump is ready to use. The recommended area of application is the arm. Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder.
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS EstroGel 0.06% is an estradiol transdermal gel. One pump depression delivers 1.25 g of gel that contains 0.75 mg estradiol. Gel: 1 pump depression of EstroGel 0.06% delivers 1.25 g of gel containing 0.75 mg estradiol ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE EstroGel 0.06% 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 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitation of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products.
Spl product data elements
Usually a list of ingredients in a drug product.EstroGel estradiol ESTRADIOL ESTRADIOL
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term, continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term, continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - EstroGel 50g Canister NDC 17139-617-40 ESTROGel ® 0.06% (estradiol gel) For Topical Use Only. A multiple-dose pump containing 50 grams (1.75 oz) Rx only ESTROGel® 0.06% (estradiol gel) label
PRINCIPAL DISPLAY PANEL - EstroGel 50g Carton NDC 17139-617-40 ESTROGel ® 0.06% (estradiol gel) For Topical Use Only. A multiple-dose pump containing 50 grams (1.75 oz) Rx only ESTROGel® 0.06% (estradiol gel) carton
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.Warnings and Precautions: Malignant Neoplasm ( 5.2 ) 12/2023
EstroGel: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise women to read the FDA-approved patient labeling (Patient Information and Instructions for Use) Vaginal Bleeding Inform postmenopausal women to report any vaginal bleeding to their healthcare provider as soon as possible [see 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 Morristown, NJ 07960 By DPT Laboratories Ltd. San Antonio, TX 78215 141332Rev122023 Utilizes EHG ® Technology ©2024 ASCEND Therapeutics ® US, LLC
Spl patient package insert
Information necessary for patients to use the drug safely and effectively.Patient Information 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 progestogen to prevent heart disease, heart attack, strokes or dementia. Using estrogens with progestogen may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots. Using estrogens with progestogen 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 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") worsening of swelling of face and tongue (angioedema) in women with a history of angioedema 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 you. In general, the addition of a progestogen is recommended for women with a uterus to reduce the chance of getting cancer of the uterus (womb). See your healthcare provider right away if you get vaginal bleeding while using EstroGel. Have a pelvic exam, breast exam and mammogram (breast x-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram (breast x-ray), you may need to have breast exams more often. If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances of getting heart disease. Ask your healthcare provider for ways to lower your chances of getting heart disease. How should I store EstroGel? Store EstroGel at room temperature between 68°F to 77°F (20°C to 25°C). Keep EstroGel and all medicines out of the reach of children. General information about the safe and effective use of EstroGel Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information leaflets. Do not use EstroGel for conditions for which it was not prescribed. Do not give EstroGel to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about EstroGel that is written for health professionals. For more information, go to www.estrogel.com , or call ASCEND Therapeutics ® US, LLC at 1-877-204-1013. What are the ingredients in EstroGel? Active ingredient: estradiol Inactive ingredients: purified water, alcohol, triethanolamine, and carbomer 934P. Instructions for Use EstroGel ® 0.06% (ĕs’ trə jĕl) (estradiol gel) Read this Instructions for Use 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. You will need the following supplies to use EstroGel: See Figure A. Figure A EstroGel is supplied in a metered-dose pump that delivers a measured amount of estradiol to your skin each time you press the pump. EstroGel is available in a 50-gram canister. Step 1. Priming the EstroGel pump Before using the EstroGel pump for the first time, the pump must be primed. The EstroGel canister contains enough medicine to allow you to prime the pump before you use it for the first time. Remove the large cap from the canister. See Figure B. Figure B Slowly push the pump all the way down 5 times. Do not use any EstroGel that came out while priming. Wash it down the sink to avoid accidental exposure to others. After priming, the EstroGel pump is ready to use. One complete press of the pump will give the same amount of EstroGel each time. Step 2. Applying EstroGel to your skin Do not allow other people to apply EstroGel to your skin for you. Apply EstroGel to clean, dry, unbroken skin. Apply EstroGel after your bath or shower. If you go swimming, try to leave as much time as possible between using your EstroGel and going swimming. Remove the small cover on the tip of the pump if you have not done so already. See Figure C. Figure C To use EstroGel, press the EstroGel pump firmly and fully 1 time into the palm of your hand. See Figure D. Figure D Using your hand, apply EstroGel to the skin of your other arm. See Figure E. Spread the gel as thinly as possible over the entire area on the inside and outside of your arm from your wrist to your shoulder. See Figure F. Figure E Figure F Do not apply EstroGel directly to your breasts or in and around your vagina. Do not massage or rub in EstroGel. Allow the gel to dry for 5 minutes before you get dressed. Step 3. After you use EstroGel Place the small cap back on the tip of the pump. Place the large cap over the top of the canister. Wash your hands right away with soap and water after applying EstroGel. This will lower the chance that the medicine will spread from your hands to other people. Do not allow others to make contact with the area of skin where you applied the gel for at least 1 hour after application. EstroGel is flammable until dry. Let EstroGel dry before smoking or going near an open flame. Step 4. Throwing away used EstroGel canisters The EstroGel 50-gram canister contains enough medicine to allow for priming your canister with up to 5 full pump depressions and delivery of 30 daily doses. After you have first primed your canister and used 30 doses, you will need to throw away the canister. Do not use the canister for more than 30 doses even though the canister may not be completely empty. You may not get the correct dose. This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration. Manufactured for: ASCEND Therapeutics ® US, LLC Morristown, NJ 07960 By DPT Laboratories Ltd. San Antonio, TX 78215 141332Rev122023 Utilizes EHG ® Technology ©2024 ASCEND Therapeutics ® US, LLC Revised: 12/2023 Figure A Figure B Figure C Figure D Figure E Figure F
|
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES 14.1 Effects on Vasomotor Symptoms in Postmenopausal Women In a placebo-controlled study, 145 postmenopausal women between 29 and 67 years of age (81.4 percent were White) were randomly assigned to receive 1.25 g of EstroGel (containing 0.75 mg of estradiol) or placebo gel for 12 weeks. Efficacy was assessed at 4 and 12 weeks of treatment. A statistically significant reduction in the frequency and severity of moderate to severe hot flushes was shown at Weeks 4 and 12. (See Table 2 ) Table 2 Mean Change from Baseline in the Number and Severity of Hot Flushes per Day, ITT Population, LOCF Number of Hot Flushes/Day (Moderate to Severe) Severity Score/Day (Mild, Moderate, Severe) Placebo n=73 EstroGel 0.06% 1.25 g n=72 Placebo n=73 EstroGel 0.06% 1.25 g n=72 Baseline Mean (SD) 11.01 (5.66) 10.33 (3.07) 2.30 (0.24) 2.36 (0.29) Week 4 Primary timepoint. Mean (SD) Mean change from baseline (SD) Diff. vs placebo P value P values from Elteren’s nonparametric test. 5.95 (5.17) -5.06 (4.91) 4.43 (4.13) -5.91 (3.68) 0.85 0.019 Statistically significantly different from placebo. 2.00 (0.63) -0.31 (0.62) 1.73 (0.73) -0.63 (0.71) 0.32 0.005 Week 12 Mean (SD) Mean change from baseline (SD) Diff. vs placebo P value 5.17 (6.52) -5.84 (4.52) 2.79 (3.70) -7.55 (3.52) 1.71 0.043 1.76 (0.84) -0.54 (0.84) 1.33 (0.97) -1.03 (0.94) 0.49 <0.001 14.2 Effects on Vulvar and Vaginal Atrophy in Postmenopausal Women Results of the vaginal wall cytology showed a significant ( P ≤0.001) increase from baseline in the percent of superficial epithelial cells at Week 12 for 1.25 g EstroGel. In contrast, no significant change from baseline was observed in the placebo group. 14.3 Women’s Health Initiative Studies The WHI enrolled approximately 27,000 predominantly healthy postmenopausal women in two substudies to assess the risks and benefits of daily oral CE (0.625 mg)‑alone or in combination with MPA (2.5 mg) compared to placebo in the prevention of certain chronic diseases. The primary endpoint was the incidence of CHD (defined as nonfatal MI, silent MI, and CHD death), with invasive breast cancer as the primary adverse outcome. A “global index” included the earliest occurrence of CHD, invasive breast cancer, stroke, PE, endometrial cancer (only in the CE plus MPA substudy), colorectal cancer, hip fracture, or death due to other causes. These substudies did not evaluate the effects of CE-alone or CE plus MPA on menopausal symptoms. WHI Estrogen-Alone Substudy The WHI estrogen-alone substudy was stopped early because an increased risk of stroke was observed, and it was deemed that no further information would be obtained regarding the risks and benefits of estrogen-alone in predetermined primary endpoints. Results of the estrogen-alone substudy, which included 10,739 women (average 63 years of age, range 50-79; 75.3 percent White, 15.1 percent Black, 6.1 percent Hispanic, 3.6 percent Other), after an average follow-up of 7.1 years are presented in Table 3 . Table 3 Relative and Absolute Risk Seen in the Estrogen-Alone Substudy of WHI Adapted from numerous WHI publications. WHI publications can be viewed at www.nhlbi.nih.gov/whi. Event Relative Risk CE vs. Placebo (95% nCI Nominal confidence intervals unadjusted for multiple looks and multiple comparisons. ) CE n = 5,310 Placebo n = 5,429 Absolute Risk per 10,000 Women-Years CHD events Results are based on centrally adjudicated data for an average follow-up of 7.1 years. 0.95 (0.78-1.16) 54 57 Non-fatal MI 0.91 (0.73-1.14) 40 43 CHD death 1.01 (0.71-1.43) 16 16 All strokes Ischemic stroke 1.33 (1.05-1.68) 1.55 (1.19-2.01) 45 38 33 25 Deep vein thrombosis Not included in “global index”. 1.47 (1.06-2.06) 23 15 Pulmonary embolism 1.37 (0.90-2.07) 14 10 Invasive breast cancer 0.80 (0.62-1.04) 28 34 Colorectal cancer 1.08 (0.75-1.55) 17 16 Hip fracture 0.65 (0.45-0.94) 12 19 Vertebral fractures 0.64 (0.44-0.93) 11 18 Lower arm/wrist fractures 0.58 (0.47-0.72) 35 59 Total fractures 0.71 (0.64-0.80) 144 197 Death due to other causes Results are based on an average follow-up of 6.8 years. All deaths, except from breast or colorectal cancer, definite or probable CHD, PE or cerebrovascular disease. 1.08 (0.88-1.32) 53 50 Overall mortality 1.04 (0.88-1.22) 79 75 Global index A subset of the events was combined in a "global index," defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes. 1.02 (0.92-1.13) 206 201 For those outcomes included in the WHI “global index” that reached statistical significance, the absolute excess risk per 10,000 women-years in the group treated with CE-alone was 12 more strokes, while the absolute risk reduction per 10,000 women‑years was 7 fewer hip fractures. 9 The absolute excess risk of events included in the "global index" was a non-significant 5 events per 10,000 women-years. There was no difference between the groups in terms of all-cause mortality . No overall difference for primary CHD events (nonfatal MI, silent MI, and CHD death) and invasive breast cancer in women receiving CE-alone compared with placebo was reported in final centrally adjudicated results from the estrogen-alone substudy, after an average follow-up of 7.1 years. See Table 3 . Centrally adjudicated results for stroke events from the estrogen-alone substudy, after an average follow-up of 7.1 years, reported no significant difference in the distribution of stroke subtype or severity, including fatal strokes, in women receiving CE-alone compared to placebo. Estrogen-alone therapy increased the risk of ischemic stroke, and this excess risk was present in all subgroups of women examined. 10 Timing of initiation of estrogen-alone therapy relative to the start of menopause may affect the overall risk benefit profile. The WHI estrogen-alone substudy stratified by age showed in women 50 to 59 years of age a non-significant trend toward reduced risk for CHD [hazard ratio (HR) 0.63 (95 percent CI, 0.36-1.09)] and overall mortality [HR 0.71 (95 percent CI, 0.46-1.11)] . WHI Estrogen Plus Progestin Substudy The WHI estrogen plus progestin substudy was stopped early. According to the predefined stopping rule, after an average follow-up of 5.6 years of treatment, the increased risk of invasive breast cancer and cardiovascular events exceeded the specified benefits included in the “global index.” The absolute excess risk of events included in the “global index” was 19 per 10,000 women-years. For those outcomes included in the WHI “global index” that reached statistical significance after 5.6 years of follow-up, the absolute excess risks per 10,000 women-years in the group treated with CE plus MPA were 7 more CHD events, 8 more strokes, 10 more PEs, and 8 more invasive breast cancers, while the absolute risk reduction per 10,000 women-years were 6 fewer colorectal cancers and 5 fewer hip fractures . Results of the CE plus MPA substudy, which included 16,608 women (average 63 years of age, range 50-79; 83.9 percent White, 6.8 percent Black, 5.4 percent Hispanic, 3.9 percent Other), are presented in Table 4 . These results reflect centrally adjudicated data after an average follow-up of 5.6 years. Table 4 Relative and Absolute Risk Seen in the Estrogen Plus Progestin Substudy of WHI at an Average of 5.6 Years Adapted from numerous WHI publications. WHI publications can be viewed at www.nhlbi.nih.gov/whi. Results are based on centrally adjudicated data. Event Relative Risk CE/MPA vs. Placebo (95% nCI Nominal confidence intervals unadjusted for multiple looks and multiple comparisons. ) CE/MPA n = 8,506 Placebo n = 8,102 Absolute Risk per 10,000 Women-Years CHD events Non-fatal MI CHD death 1.23 (0.99-1.53) 1.28 (1.00-1.63) 1.10 (0.70-1.75) 41 31 8 34 25 8 All strokes Ischemic stroke 1.31 (1.03-1.68) 1.44 (1.09-1.90) 33 26 25 18 Deep vein thrombosis Not included in “global index”. 1.95 (1.43-2.67) 26 13 Pulmonary embolism 2.13 (1.45-3.11) 18 8 Invasive breast cancer Includes metastatic and non-metastatic breast cancer, with the exception of in‑ situ breast cancer. 1.24 (1.01-1.54) 41 33 Colorectal cancer 0.61 (0.42-0.87) 10 16 Endometrial cancer 0.81 (0.48-1.36) 6 7 Cervical cancer 1.44 (0.47-4.42) 2 1 Hip fracture 0.67 (0.47-0.96) 11 16 Vertebral fractures 0.65 (0.46-0.92) 11 17 Lower arm/wrist fractures 0.71 (0.59-0.85) 44 62 Total fractures 0.76 (0.69-0.83) 152 199 Overall mortality All deaths, except from breast or colorectal cancer, definite or probable CHD, PE or cerebrovascular disease. 1.00 (0.83-1.19) 52 52 Global Index A subset of the events was combined in a "global index," defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes. 1.13 (1.02-1.25) 184 165 Timing of initiation of estrogen plus progestin therapy relative to the start of menopause may affect the overall risk benefit profile. The WHI estrogen plus progestin substudy stratified by age showed in women 50 to 59 years of age a non-significant trend toward reduced risk for overall mortality [HR 0.69 (95 percent CI, 0.44-1.07)] . 14.4 Women's Health Initiative Memory Study The WHIMS estrogen-alone ancillary study of WHI enrolled 2,947 predominantly healthy hysterectomized postmenopausal women 65 years of age and older (45 percent were 65 to 69 years of age, 36 percent were 70 to 74 years of age, and 19 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg)-alone on the incidence of probable dementia (primary outcome) compared to placebo. After an average follow-up of 5.2 years, the relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83-2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years. Probable dementia as defined in the study included Alzheimer’s disease (AD), vascular dementia (VaD) and mixed type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo group was AD. Since the ancillary study was 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 Use in Specific Populations ( 8.5 )]. The WHIMS estrogen plus progestin ancillary study enrolled 4,532 predominantly healthy postmenopausal women 65 years of age and older (47 percent were 65 to 69 years of age, 35 percent were 70 to 74 years of age, and 18 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg) plus MPA (2.5 mg) on the incidence of probable dementia (primary outcome) compared to placebo. After an average follow-up of 4 years, the relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21-3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years. Probable dementia as defined in the study included AD, VaD and mixed type (having features of both AD and VaD). The most common classification of probable dementia in the treatment group and the placebo group was AD. Since the ancillary study was 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 Use in Specific Populations ( 8.5 )]. When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19-2.60). Differences between groups became apparent in the first year of treatment. It is unknown whether these findings apply to younger postmenopausal women [see Warnings and Precautions ( 5.3 ), and Use in Specific Populations ( 8.5 )].
References
This field may contain references when prescription drug labeling must summarize or otherwise relay on a recommendation by an authoritative scientific body, or on a standardized methodology, scale, or technique, because the information is important to prescribing decisions.15 REFERENCES 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.
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing EstroGel to determine whether those over 65 years of age differ from younger subjects in their response to EstroGel. 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 )] .
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use EstroGel is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary EstroGel is not indicated for use in pregnancy . There are no data with the use of EstroGel in pregnant women, however, epidemiologic studies and meta-analysis have not found an increased risk of genital or non-genital birth defects (including cardiac anomalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary EstroGel is not indicated for use in pregnancy . There are no data with the use of EstroGel in pregnant women, however, epidemiologic studies and meta-analysis have not found an increased risk of genital or non-genital birth defects (including cardiac anomalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogens and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.3 Lactation 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 development and health benefits of breastfeeding should be considered along with the mother’s clinical need for EstroGel and any potential adverse effects on the breastfed child from EstroGel or from the underlying maternal condition. 8.4 Pediatric Use EstroGel is not indicated for use in pediatric patients. Clinical studies have not been conducted in the pediatric population. 8.5 Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing EstroGel to determine whether those over 65 years of age differ from younger subjects in their response to EstroGel. 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 )] .
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied EstroGel is a clear, colorless, hydroalcoholic 0.06 percent estradiol gel supplied in a non‑aerosol, metered-dose pump. The pump consists of an LDPE inner liner encased in rigid plastic with a resealable polypropylene cap. EstroGel is available in a 50-gram (1.75 oz) size. Each individually packaged 50-gram pump contains 50 grams of gel and can deliver 30 metered 1.25-g doses. NDC: 17139-617-40............................. (50-gram pump) 16.2 Storage and Handling Keep out of reach of children. 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].
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.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 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. WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER See full prescribing information for complete boxed warning Estrogen-Alone Therapy There is an increased risk of endometrial cancer in women with a uterus who use unopposed estrogens ( 5.2 ) The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) ( 5.1 ) The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 ) Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) Estrogen Plus Progestin Therapy The WHI estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), DVT, stroke, and myocardial infarction (MI) ( 5.1 ) The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer ( 5.2 ) The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older ( 5.3 ) Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 )
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API