estrogens, conjugated .3 mg Tablet, Film Coated, 100-count — NDC 50742-387-01 (Billing 50742-0387-01)
This is a package of 100 tablets of estrogens, conjugated .3 mg Tablet, Film Coated from Ingenus Pharmaceuticals, LLC, marketed since Oct 2025 and currently FDA-listed; retail pharmacies pay about $5.37 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.
NDC database record
One package, one record: these facts belong to NDC 50742-387-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 50742 labeler · 387 product · 01 package
- Package marketed since
- Oct 16, 2025
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2027
- Billing quantity
- 100 EA per package
- Barcode (UPC)
- 0350742387014, 0350742389018, 0350742388011
- Medicaid fills, this package
- 1,550 prescriptions in the last four reported quarters
- FDA record last changed
- Sep 10, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 003211
- GCN: 10943
- HICL (First Databank): 001424
- AHFS class code: 68:16.04.00
- RxCUI (RxNorm): 197660
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Estrogen class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Estrogen may be used for the following: to treat hot flushes ('hot flashes'; sudden strong feelings of heat and sweating) in women who are experiencing menopause ('change of life', the end of monthly menstrual periods) to treat vaginal dryness, itching, or burning to prevent osteoporosis (a condition in which the bones become thin and weak and break easily) in women who are experiencing or have experienced menopause to relieve symptoms of low estrogen in young women who do not produce enough estrogen naturally to relieve the symptoms of certain types of breast and prostate (a male repro...
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $5.373 | $537.28 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $5.50 | $549.85 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $6.31 | $630.83 / 100 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 50742-0387-01 You're viewing this Main listing | 100 TABLET, FILM COATED in 1 BOTTLE | $5.37 / ea | $537.28 | 2025-10-16 | — | Active |
| 50742-0387-10 50742-387-10 | 1000 TABLET, FILM COATED in 1 BOTTLE | — | — | 2025-10-16 | — | Active |
You're viewing the smallest of 2 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 50742-0387-10?
What NDC number is used to bill for this package of estrogens, conjugated .3 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| estrogens, conjugated .3 mgthis 50742-0387-01 | Ingenus | 100 tablets | $5.373 | AB | Availability likely | — |
| Conjugated Estrogens .3 mg 66993-0295-02 | Prasco | 100 tablets | $5.373 | AB | Availability likely | — |
| Premarin .3 mg 00046-1100-52 | Wyeth | 5 tablets | — | AB | FDA listed | — |
| Premarin .3 mg 50090-1853-03 | A-S | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Code | What it grants | Expires |
|---|---|---|
| CGT | FDA-granted marketing exclusivity | Apr 15, 2026 |
| CGT | FDA-granted marketing exclusivity | Apr 15, 2026 |
| CGT | FDA-granted marketing exclusivity | Apr 15, 2026 |
Is there a generic version of CONJUGATED ESTROGENS 0.3 MG TB?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Ingenus Pharmaceuticals, LLC labeler code 50742
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- prednisolone sodium phosphate ODT 15 mg Tablet, Orally Disintegrating NDC 50742-384-12
- prednisolone sodium phosphate ODT 30 mg Tablet, Orally Disintegrating NDC 50742-385-12
- Sucralfate 1 g/10mL Suspension NDC 50742-386-42
- estrogens, conjugated .45 mg Tablet, Film Coated NDC 50742-388-01
- estrogens, conjugated .625 mg Tablet, Film Coated NDC 50742-389-01
- estrogens, conjugated .9 mg Tablet, Film Coated NDC 50742-390-01
- estrogens, conjugated 1.25 mg Tablet, Film Coated NDC 50742-391-01
- Albuterol Sulfate .63 mg/3mL Solution NDC 50742-392-25
- Albuterol Sulfate 1.25 mg/3mL Solution NDC 50742-393-25
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA See full prescribing information for complete boxed warning. Estrogen-Alone Therapy • There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens ( 5.2 ) • Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) • 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 ) Estrogen Plus Progestin Therapy • Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia ( 5.1 , 5.3 ) • The WHI estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism (PE), 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 ) Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.
Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ]. Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3) , and Clinical Studies (14.5, 14.6) ] .
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 (14.5) ]. 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 (14.6) ] . In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.1, 5.3) , and Clinical Studies (14.5 , 14.6) ]. 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 (14.5) ] .
The WHIMS estrogen plus progestin ancillary study of the WHI… [Excerpted — this section continues on DailyMed.]
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Conjugated estrogens tablets is a mixture of estrogens indicated for: •Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause. ( 1.1 ) •Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) •Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure ( 1.3 ) •Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease ( 1.4 ) •Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (for Palliation Only) ( 1.5 ) •Prevention of Postmenopausal Osteoporosis ( 1.6 )
1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause
1.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Limitations of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, topical vaginal products should be considered.
1.3Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure
1.4Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease
1.5Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (for Palliation Only)
1.6Prevention of Postmenopausal Osteoporosis Limitations of Use When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Generally, when estrogen therapy is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer [see Boxed Warning ]. A woman without a uterus does not need progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.16) ] .
Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. Conjugated estrogens tablets may be taken without regard to meals. •Daily administration of 0.3 mg, 0.45 mg, and 0.625 mg ( 2.1 , 2.2 , 2.3 , 2.5 , 2.6 ) •Cyclic administration of 0.3 mg, and 0.625 mg ( 2.1 , 2.2 , 2.3 )
2.1Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Patients should be treated with the lowest effective dose. Generally, women should be started at 0.3 mg conjugated estrogens tablets daily. Subsequent dosage adjustment may be made based upon the individual patient response.
This dose should be periodically reassessed by the healthcare provider. Conjugated estrogens tablets therapy may be given continuously, with no interruption in therapy, or in cyclical regimens (regimens such as 25 days on drug followed by 5 days off drug), as is medically appropriate on an individual basis.
2.2Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause Patients should be treated with the lowest effective dose. Generally, women should be started at 0.3 mg conjugated estrogens tablets daily. Subsequent dosage adjustment may be made based upon the individual patient response.
This dose should be periodically reassessed by the healthcare provider. Conjugated estrogens tablets therapy may be given continuously, with no interruption in therapy, or in cyclical regimens (regimens such as 25 days on drug followed by 5 days off drug), as is medically appropriate on an individual basis.
2.3Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure Conjugated estrogens tablets therapy should be initiated and maintained with the lowest effective dose to achieve clinical goals. Female hypogonadism: 0.3 mg or 0.625 mg daily, administered cyclically (e.g., three weeks on and one week off). Doses are adjusted depending on the severity of symptoms and responsiveness of the endometrium [ see Clinical Studies (14.4) ].
Female castration or primary ovarian failure: 1.25 mg daily, cyclically. Adjust dosage, upward or downward, according to severity of symptoms and response of the patient. For maintenance, adjust dosage to lowest level that will provide effective control.
2.4Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease Suggested dosage is 10 mg three times daily, for a period of at least three months.
2.5Treatment of Advanced Androgen-Dependent Carcinoma of the Prostate (for Palliation Only) 2x0.625 mg to 4x0.625 mg three times daily. The effectiveness of therapy can be judged by phosphatase determinations as well as by symptomatic improvement of the patient.
2.6Prevention of Postmenopausal Osteoporosis Conjugated estrogens tablets therapy may be given continuously, with no interruption in therapy, or in cyclical regimens (regimens such as 25 days on drug followed by 5 days off drug), as is medically appropriate on an individual basis. Patients should be treated with the lowest effective dose. Generally, women should be started at 0.3 mg conjugated estrogens tablets daily.
Subsequent dosage adjustment may be made based upon the individual clinical and bone mineral density responses. This dose should be periodically reassessed by the healthcare provider.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Conjugated estrogens tablets, USP Tablet Strength Tablet Shape/Color Debossed 0.3mg oval biconvex/ green "CT1" on one side and "NL" on the other side 0.45mg oval biconvex/ blue "CT2" on one side and "NL" on the other side 0.625mg oval biconvex/ peach "CT3" on one side and "NL" on the other side Tablets: 0.3 mg, 0.45 mg, and 0.625 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Conjugated estrogens tablets therapy is contraindicated in individuals with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.2 )] • Breast cancer or a history of breast cancer except in appropriately selected patients being treated for metastatic disease [see Warnings and Precautions ( 5.2 )] • Estrogen-dependent neoplasia [see Warnings and Precautions ( 5.2 )] • Active DVT, PE, or a history of these conditions [see Warnings and Precautions ( 5.1 )] • Active arterial thromboembolic disease (for example stroke and MI), or a history of these conditions [see Warnings and Precautions ( 5.1 )] • Known anaphylactic reaction or angioedema with conjugated estrogens tablets [see Warnings and Precautions ( 5.7 , 5.15 )] • Hepatic impairment or disease [see Warnings and Precautions ( 5.11 )] • Protein C, protein S or antithrombin deficiency, or other known thrombophilic disorders. •Undiagnosed abnormal genital bleeding ( 4 ) •Breast cancer or history of breast cancer except in appropriately selected patients being treated for metastatic diseases ( 4 , 5.2 ) •Estrogen-dependent neoplasia ( 4 , 5.2 ) •Active DVT, PE, or a history of these conditions ( 4 , 5.1 ) •Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.1 ) •Known anaphylactic reaction or angioedema with conjugated estrogens tablets ( 5.7 , 5.15 ) •Hepatic impairment or disease ( 4 , 5.11 ) •Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS •Estrogens increase the risk of gallbladder disease ( 5.4 ) •Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.10 , 5.11 ) •Monitor thyroid function in patients on thyroid replacement therapy ( 5.12 , 5.19 )
5.1Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke and MI has been reported with estrogen plus progestin therapy. Should any of these events occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately.
Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years).
The increase in risk was demonstrated in Year 1 and persisted [see Clinical Studies (14.5) ] . Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years).
1 In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years) [see Clinical Studies (14.5) ] . The increase in risk was demonstrated after the first year and persisted. 1 Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately.
Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo 2 [see Clinical Studies (14.5)] . Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years). 1 In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years).
1 An increase in relative risk was demonstrated in Year 1, and a trend toward decreasing relative risk was reported in years 2 through 5 [see Clinical Studies (14.5) ] . In postmenopausal women with documented heart disease (n = 2,763, average 66.7 years of age), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established CHD.
There were more CHD events in the CE plus MPA-treated group than in the placebo group in Year 1, but not during the subsequent years. Two thousand, three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall.
Rates of CHD events were comparable among women in the CE (0.625… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in labeling: •Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.1) ] •Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.2) ] Most common adverse reactions (≥ 5%) are: abdominal pain, asthenia, pain, back pain, headache, flatulence, nausea, depression, insomnia, breast pain, endometrial hyperplasia, leucorrhea, vaginal hemorrhage, and vaginitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC Toll-Free at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Study 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. During the first year of a 2-year clinical trial with 2,333 postmenopausal women with a uterus between 40 and 65 years of age (88% Caucasian), 1,012 women were treated with CE, and 332 were treated with placebo. Table 1 summarizes treatment-related adverse reactions that occurred at a rate of ≥ 1% in any treatment group.
Table 1: Treatment-Related Adverse Reactions at a Frequency ≥1% Conjugated estrogens tablets 0.625 mg (n=348) Conjugated estrogens tablets 0.45 mg (n=338) Conjugated estrogens tablets 0.3 mg (n=326) Placebo (n=332) Body as a whole Abdominal pain 38 (11) 28 (8) 30 (9) 21 (6) Asthenia 16 (5) 8 (2) 14 (4) 3 (1) Back pain 18 (5) 11 (3) 13 (4) 4 (1) Chest pain 2 (1) 3 (1) 4 (1) 2 (1) Generalized edema 7 (2) 6 (2) 4 (1) 8 (2) Headache 45 (13) 47 (14) 44 (13) 46 (14) Moniliasis 5 (1) 4 (1) 4 (1) 1 (0) Pain 17 (5) 10 (3) 12 (4) 14 (4) Pelvic pain 10 (3) 9 (3) 8 (2) 4 (1) Cardiovascular system Hypertension 4 (1) 4 (1) 7 (2) 5 (2) Migraine 7 (2) 1 (0) 0 3 (1) Palpitation 3 (1) 3 (1) 3 (1) 4 (1) Vasodilatation 2 (1) 2 (1) 3 (1) 5 (2) Digestive system Constipation 7 (2) 6 (2) 4 (1) 3 (1) Diarrhea 4 (1) 5 (1) 5 (2) 8 (2) Dyspepsia 7 (2) 5 (1) 6 (2) 14 (4) Eructation 1 (0) 1 (0) 4 (1) 1 (0) Flatulence 22 (6) 18 (5) 13 (4) 8 (2) Increased appetite 4 (1) 1 (0) 1 (0) 2 (1) Nausea 16 (5) 10 (3) 15 (5) 16 (5) Metabolic and nutritional Hyperlipidemia 2 (1) 4 (1) 3 (1) 2 (1) Peripheral edema 5 (1) 2 (1) 4 (1) 3 (1) Weight gain 11 (3) 10 (3) 8 (2) 14 (4) Musculoskeletal system Arthralgia 6 (2) 3 (1) 2 (1) 5 (2) Leg cramps 10 (3) 5 (1) 9 (3) 4 (1) Myalgia 2 (1) 1 (0) 4 (1) 1 (0) Nervous system Anxiety 6 (2) 4 (1) 2 (1) 4 (1) Depression 17 (5) 15 (4) 10 (3) 17 (5) Dizziness 9 (3) 7 (2) 4 (1) 5 (2) Emotional lability 3 (1) 4 (1) 5 (2) 8 (2) Hypertonia 1 (0) 1 (0) 5 (2) 3 (1) Insomnia 16 (5) 10 (3) 13 (4) 14 (4) Nervousness 9 (3) 12 (4) 2 (1) 6 (2) Skin and appendages Acne 3 (1) 1 (0) 8 (2) 3 (1) Alopecia 6 (2) 6 (2) 5 (2) 2 (1) Hirsutism 4 (1) 2 (1) 1 (0) 0 Pruritus 11 (3) 11 (3) 10 (3) 3 (1) Rash 6 (2) 3 (1) 1 (0) 2 (1) Skin discoloration 4 (1) 2 (1) 0 1 (0) Sweating 4 (1) 1 (0) 3 (1) 4 (1) Urogenital system Breast disorder 6 (2) 3 (1) 3 (1) 6 (2) Breast enlargement 3 (1) 4 (1) 7 (2) 3 (1) Breast neoplasm 4 (1) 4 (1) 7 (2) 7 (2) Breast pain 37 (11) 39 (12) 24 (7) 26 (8) Cervix disorder 8 (2) 4 (1) 5 (2) 0 Dysmenorrhea 12 (3) 10 (3) 4 (1) 2 (1) Endometrial disorder 4 (1) 2 (1) 2 (1) 0 Endometrial hyperplasia 16 (5) 8 (2) 1 (0) 0 Leukorrhea 17 (5) 17 (5) 12 (4) 6 (2) Metrorrhagia 11 (3) 4 (1) 3 (1) 1 (0) Urinary tract infection 1 (0) 2 (1) 1 (0) 4 (1) Uterine fibroids enlarged 6 (2) 1 (0) 2 (1) 2 (1) Uterine spasm 11 (3) 5 (1) 3 (1) 2 (1) Vaginal dryness 1 (0) 2 (1) 1 (0) 6 (2) Vaginal hemorrhage 46 (13) 13 (4) 6 (2) 0 Vaginal moniliasis 14 (4) 10 (3) 12 (4) 5 (2) Vaginitis 18 (5) 7 (2) 9 (3) 1 (0)
6.2Postmarketing Experience The following additional adverse reactions have been identified during post-approval use of conjugated estrogens tablets. Because these reactions are reported voluntarily from a population of… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Data from a single-dose drug-drug interaction study involving CE and MPA indicate that the pharmacokinetic disposition of both drugs is not altered when the drugs are coadministered. No other clinical drug-drug interaction studies have been conducted with CE. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism ( 7.1 )
7.1Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St.
John’s Wort ( Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects.
🔄 Drug / Laboratory Test Interactions ▾
5.19Drug-Laboratory Test Interactions • Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. • Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T 4 levels (by column or by radioimmunoassay) or T 3 levels by radioimmunoassay.
T 3 resin uptake is decreased, reflecting the elevated TBG. Free T 4 and free T 3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone. • Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively.
Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). • Increased plasma high-density lipoprotein (HDL) and HDL 2 cholesterol subfraction, reduced low-density lipoprotein (LDL) cholesterol, increased triglyceride levels. • Impaired glucose tolerance.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS •Lactation: Estrogen administration to lactating women has been shown to decrease the quantity and quality of breast milk ( 8.2 ) •Geriatric Use: An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative ( 5.3 , 8.5 )
8.1Pregnancy Risk Summary Conjugated estrogens tablets is not indicated for use during pregnancy. There are no data with the use of conjugated estrogens tablet in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
8.2Lactation Risk Summary Estrogens and progestins and metabolites are present in human milk. These hormones can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well established.
The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for conjugated estrogens tablets and any potential adverse effects on the breast-fed child from conjugated estrogens tablets or from the underlying maternal condition.
8.4Pediatric Use Estrogen therapy has been used for the induction of puberty in adolescents with some forms of pubertal delay. Safety and effectiveness in pediatric patients have not otherwise been established. Large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, which could result in short stature if treatment is initiated before the completion of physiologic puberty in normally developing children.
If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone maturation and effects on epiphyseal centers is recommended during estrogen administration. Estrogen treatment of prepubertal girls also induces premature breast development and vaginal cornification, and may induce vaginal bleeding. In boys, estrogen treatment may modify the normal pubertal process and induce gynecomastia.
8.5Geriatric Use There have not been sufficient numbers of geriatric patients involved in studies utilizing conjugated estrogens tablets to determine whether those over 65 years of age differ from younger subjects in their response to conjugated estrogens tablets. The Women's Health Initiative Study 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 Clinical Studies (14.5) ] . 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 Clinical Studies (14.5) ] .
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 (14.6) ] . 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 (14.6) ].
8.6Renal Impairment The effect of renal impairment on the pharmacokinetics of conjugated estrogens tablets has not been studied.
8.7Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of conjugated… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Conjugated estrogens tablets is not indicated for use during pregnancy. There are no data with the use of conjugated estrogens tablet in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
🧒 Pediatric Use ▾
8.4Pediatric Use Estrogen therapy has been used for the induction of puberty in adolescents with some forms of pubertal delay. Safety and effectiveness in pediatric patients have not otherwise been established. Large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, which could result in short stature if treatment is initiated before the completion of physiologic puberty in normally developing children.
If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone maturation and effects on epiphyseal centers is recommended during estrogen administration. Estrogen treatment of prepubertal girls also induces premature breast development and vaginal cornification, and may induce vaginal bleeding. In boys, estrogen treatment may modify the normal pubertal process and induce gynecomastia.
🧓 Geriatric Use ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric patients involved in studies utilizing conjugated estrogens tablets to determine whether those over 65 years of age differ from younger subjects in their response to conjugated estrogens tablets. The Women's Health Initiative Study 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 Clinical Studies (14.5) ] . 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 Clinical Studies (14.5) ] .
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 (14.6) ] . 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 (14.6) ].
🆘 Overdosage ▾
10 OVERDOSAGE Overdosage of estrogen may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness and fatigue, and withdrawal bleeding may occur in women. Treatment of overdose consists of discontinuation of conjugated estrogens tablets therapy with institution of appropriate symptomatic care.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two 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 gonadotropins seen in postmenopausal women.
12.2Pharmacodynamics There are no pharmacodynamic data for conjugated estrogens tablets.
12.3Pharmacokinetics Absorption Conjugated estrogens are water-soluble and are absorbed from the gastrointestinal tract after release from the drug formulation. The conjugated estrogens tablets releases CE slowly over several hours. Table 2 summarizes the mean pharmacokinetic parameters for unconjugated and CE following administration of 1 × 0.625 mg and 1 × 1.25 mg tablets to healthy postmenopausal women.
Food effect: The pharmacokinetics of conjugated estrogens tablets 0.45 mg and 1.25 mg tablets were assessed following a single dose with a high-fat breakfast and with fasting administration. The C max and AUC of estrogens were altered approximately 3–13%. The changes to C max and AUC are not considered clinically meaningful, therefore conjugated estrogens tablets may be taken without regard to meals.
Table 2: Pharmacokinetic Parameters for Conjugated Estrogens Tablets Pharmacokinetic Profile of Unconjugated Estrogens Following a Dose of 1 × 0.625 mg PK Parameter Arithmetic Mean (%CV) C max (pg/mL) t max (h) t 1/2 (h) AUC (pg∙h/mL) Estrone 87 (33) 9.6 (33) 50.7 (35) 5557 (59) Baseline-adjusted estrone 64 (42) 9.6 (33) 20.2 (40) 1723 (52) Equilin 31 (38) 7.9 (32) 12.9 (112) 602 (54) Pharmacokinetic Profile of CE Following a Dose of 1 × 0.625 mg PK Parameter Arithmetic Mean (%CV) C max (ng/mL) t max (h) t 1/2 (h) AUC (ng∙h/mL) Total Estrone 2.7 (43) 6.9 (25) 26.7 (33) 75 (52) Baseline-adjusted total estrone 2.5 (45) 6.9 (25) 14.8 (35) 46 (48) Total Equilin 1.8 (56) 5.6 (45) 11.4 (31) 27 (56) Pharmacokinetic Profile of Unconjugated Estrogens Following a Dose of 1 × 1.25 mg PK Parameter Arithmetic Mean (%CV) C max (pg/mL) t max (h) t 1/2 (h) AUC (pg∙h/mL) Estrone 124 (30) 10.0 (32) 38.1 (37) 6332 (44) Baseline-adjusted estrone 102 (35) 10.0 (32) 19.7 (48) 3159 (53) Equilin 59 (43) 8.8 (36) 10.9 (47) 1182 (42) Pharmacokinetic Profile of CE Following a Dose of 1 × 1.25 mg PK Parameter Arithmetic Mean (%CV) C max (ng/mL) t max (h) t 1/2 (h) AUC (ng∙h/mL) Total Estrone 4.5 (39) 8.2 (58) 26.5 (40) 109 (46) Baseline-adjusted total estrone 4.3 (41) 8.2 (58) 17.5 (41) 87 (44) Total equilin 2.9 (42) 6.8 (49) 12.5 (34) 48 (51) 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 concentration in the sex hormone target organs. Estrogens circulate in the blood largely bound to SHBG and albumin. Metabolism Exogenous estrogens are metabolized in the same manner as endogenous estrogens.
Circulating estr… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Endogenous estrogens are largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone in the peripheral tissues. Thus, estrone and the sulfate-conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues.
To date, two 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 gonadotropins seen in postmenopausal women.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Conjugated estrogens tablets, USP • Each green oval biconvex coated tablet contains 0.3 mg, in bottles of 100 (NDC 50742-387-01) and 1,000 (NDC 50742-387-10). • Each blue oval biconvex coated tablet contains 0.45 mg, in bottles of 100 (NDC 50742-388-01) and 1,000 (NDC 50742-388-10). • Each peach oval biconvex coated tablet contains 0.625 mg, in bottles of 100 (NDC 50742-389-01) and 1,000 (NDC 50742-389-10).
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a well-closed container, as defined in the USP.
📦 Storage and Handling ▾
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a well-closed container, as defined in the USP.
📋 Description ▾
11 DESCRIPTION Conjugated estrogens tablets, USP for oral administration contains a mixture of CE purified from pregnant mares' urine and consists of the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares' urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate. It contains concomitant components as sodium sulfate conjugates, 17α-dihydroequilin, 17α-estradiol, and 17β-dihydroequilin.
Tablets for oral administration are available in 0.3 mg, 0.45 mg, and 0.625 mg strengths of CE. Conjugated estrogens tablets USP, 0.3 mg, 0.45 mg, and 0.625 mg tablets also contain the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, sodium acetate anhydrous, and titanium dioxide. Each tablet strength contains the following colors: Tablet strength Tablet color contains 0.3 mg D&C Yellow #10 Aluminum Lake and FD&C Blue #2 Aluminum Lake 0.45 mg FD&C Blue #1 Aluminum Lake, FD&C Red #40 Aluminum Lake, and FD&C Yellow #6 Aluminum Lake 0.625 mg FD&C Blue #2 Aluminum Lake and FD&C Red #40 Aluminum Lake FDA approved dissolution test specifications differ from USP.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patients to read the FDA-approved patient labeling ( Patient Information ).
17.1Vaginal Bleeding Inform postmenopausal women of the importance of reporting vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions (5.2) ] .
17.2Possible Serious Adverse Reactions with Estrogens Inform postmenopausal women of possible serious adverse reactions of estrogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.1 , 5.2 , 5.3) ] .
17.3Possible Less Serious but Common Adverse Reactions with Estrogens Inform postmenopausal women of possible less serious but common adverse reactions of estrogen therapy such as headache, breast pain and tenderness, nausea and vomiting. Iss: 05/2026 I0152 Rev C Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32811-7193 Product of China ingenus-logo
🍼 Nursing Mothers ▾
8.2Lactation Risk Summary Estrogens and progestins and metabolites are present in human milk. These hormones can reduce milk production in breast-feeding women. This reduction can occur at any time but is less likely to occur once breast-feeding is well established.
The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for conjugated estrogens tablets and any potential adverse effects on the breast-fed child from conjugated estrogens tablets or from the underlying maternal condition.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Conjugated estrogens are water-soluble and are absorbed from the gastrointestinal tract after release from the drug formulation. The conjugated estrogens tablets releases CE slowly over several hours. Table 2 summarizes the mean pharmacokinetic parameters for unconjugated and CE following administration of 1 × 0.625 mg and 1 × 1.25 mg tablets to healthy postmenopausal women.
Food effect: The pharmacokinetics of conjugated estrogens tablets 0.45 mg and 1.25 mg tablets were assessed following a single dose with a high-fat breakfast and with fasting administration. The C max and AUC of estrogens were altered approximately 3–13%. The changes to C max and AUC are not considered clinically meaningful, therefore conjugated estrogens tablets may be taken without regard to meals.
Table 2: Pharmacokinetic Parameters for Conjugated Estrogens Tablets Pharmacokinetic Profile of Unconjugated Estrogens Following a Dose of 1 × 0.625 mg PK Parameter Arithmetic Mean (%CV) C max (pg/mL) t max (h) t 1/2 (h) AUC (pg∙h/mL) Estrone 87 (33) 9.6 (33) 50.7 (35) 5557 (59) Baseline-adjusted estrone 64 (42) 9.6 (33) 20.2 (40) 1723 (52) Equilin 31 (38) 7.9 (32) 12.9 (112) 602 (54) Pharmacokinetic Profile of CE Following a Dose of 1 × 0.625 mg PK Parameter Arithmetic Mean (%CV) C max (ng/mL) t max (h) t 1/2 (h) AUC (ng∙h/mL) Total Estrone 2.7 (43) 6.9 (25) 26.7 (33) 75 (52) Baseline-adjusted total estrone 2.5 (45) 6.9 (25) 14.8 (35) 46 (48) Total Equilin 1.8 (56) 5.6 (45) 11.4 (31) 27 (56) Pharmacokinetic Profile of Unconjugated Estrogens Following a Dose of 1 × 1.25 mg PK Parameter Arithmetic Mean (%CV) C max (pg/mL) t max (h) t 1/2 (h) AUC (pg∙h/mL) Estrone 124 (30) 10.0 (32) 38.1 (37) 6332 (44) Baseline-adjusted estrone 102 (35) 10.0 (32) 19.7 (48) 3159 (53) Equilin 59 (43) 8.8 (36) 10.9 (47) 1182 (42) Pharmacokinetic Profile of CE Following a Dose of 1 × 1.25 mg PK Parameter Arithmetic Mean (%CV) C max (ng/mL) t max (h) t 1/2 (h) AUC (ng∙h/mL) Total Estrone 4.5 (39) 8.2 (58) 26.5 (40) 109 (46) Baseline-adjusted total estrone 4.3 (41) 8.2 (58) 17.5 (41) 87 (44) Total equilin 2.9 (42) 6.8 (49) 12.5 (34) 48 (51) 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 concentration in the sex hormone target organs. Estrogens circulate in the 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 exists as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens. Excretion Estradiol, estrone, and estriol are excreted in the urine, along with glucuronide and sulfate conjugates.
Use in Specific Populations No pharmacokinetic studies were conducted with conjugated estrogens tablets in specific populations, including patients with renal or hepatic impairment.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics There are no pharmacodynamic data for conjugated estrogens tablets.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Effects on Vasomotor Symptoms In the first year of the Health and Osteoporosis, Progestin and Estrogen (HOPE) Study, a total of 2,805 postmenopausal women (average age 53.3 ± 4.9 years) were randomly assigned to one of eight treatment groups of either placebo or CE, with or without MPA. Efficacy for vasomotor symptoms was assessed during the first 12 weeks of treatment in a subset of symptomatic women (n = 241) who had at least seven moderate to severe hot flushes daily, or at least 50 moderate to severe hot flushes during the week before randomization.
Conjugated estrogens tablets (0.3 mg, 0.45 mg, and 0.625 mg tablets) was shown to be statistically better than placebo at weeks 4 and 12 for relief of both frequency and severity of moderate to severe vasomotor symptoms. Table 3 shows the adjusted mean number of hot flushes in the conjugated estrogens tablets 0.3 mg, 0.45 mg, and 0.625 mg and placebo groups during the initial 12-week period. Table 3: Summary Tabulation of the Number of Hot Flushes Per Day – Mean Values and Comparisons Between the Active Treatment Groups and the Placebo Group: Patients with at Least 7 Moderate to Severe Flushes Per Day or at Least 50 Per Week at Baseline, Last Observation Carried Forward (LOCF) Treatment (No. of Patients) ---------------No. of Hot Flushes/Day--------------- Time Period (week) Baseline Mean ± SD Observed Mean ± SD Mean Change ± SD p-Values vs Placebo Based on analysis of covariance with treatment as factor and baseline as covariate.
0.625 mg CE (n = 27) 4 12.29 ± 3.89 1.95 ± 2.77 -10.34 ± 4.73 <0.001 12 12.29 ± 3.89 0.75 ± 1.82 -11.54 ± 4.62 <0.001 0.45 mg CE (n = 32) 4 12.25 ± 5.04 5.04 ± 5.31 -7.21 ± 4.75 <0.001 12 12.25 ± 5.04 2.32 ± 3.32 -9.93 ± 4.64 <0.001 0.3 mg CE (n = 30) 4 13.77 ± 4.78 4.65 ± 3.71 -9.12 ± 4.71 <0.001 12 13.77 ± 4.78 2.52 ± 3.23 -11.25 ± 4.60 <0.001 Placebo (n = 28) 4 11.69 ± 3.87 7.89 ± 5.28 -3.80 ± 4.71 - 12 11.69 ± 3.87 5.71 ± 5.22 -5.98 ± 4.60 -
14.2Effects on Vulvar and Vaginal Atrophy Results of vaginal maturation indexes at cycles 6 and 13 showed that the differences from placebo were statistically significant (p < 0.001) for all treatment groups. ( CE alone and CE/MPA treatment groups).
14.3Effects on Bone Mineral Density Health and Osteoporosis, Progestin and Estrogen (HOPE) Study The HOPE study was a double-blind, randomized, placebo/active-drug-controlled, multicenter study of healthy postmenopausal women with an intact uterus. Subjects (mean age 53.3 ± 4.9 years) were 2.3 ± 0.9 years on average since menopause and took one 600 mg tablet of elemental calcium (Caltrate™) daily. Subjects were not given Vitamin D supplements.
They were treated with conjugated estrogens tablets 0.625 mg, 0.45 mg, 0.3 mg, or placebo. Prevention of bone loss was assessed by measurement of bone mineral density (BMD), primarily at the anteroposterior lumbar spine (L 2 to L 4 ). Secondarily, BMD measurements of the total body, femoral neck, and trochanter were also analyzed.
Serum osteocalcin, urinary calcium, and N-telopeptide were used as bone turnover markers (BTM) at cycles 6, 13, 19, and 26. Intent-to-treat subjects All active treatment groups showed significant differences from placebo in each of the four BMD endpoints at cycles 6, 13, 19, and 26. The mean percent increases in the primary efficacy measure (L 2 to L 4 BMD) at the final on-therapy evaluation (cycle 26 for those who completed and the last available evaluation for those who discontinued early) were 2.46% with 0.625 mg, 2.26% with 0.45 mg, and 1.13% with 0.3 mg.
The placebo group showed a mean percent decrease from baseline at the final evaluation of 2.45%. These results show that the lower dosages of conjugated estrogens tablets were effective in increasing L 2 to L 4 BMD compared with placebo, and therefore support the efficacy of the lower doses. The analysis for the other three BMD endpoints yielded mean percent changes from baseline in femoral trochanter that were gener… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, 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.[ see Warnings and Precautions (5.2) ] .
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, 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.[ see Warnings and Precautions (5.2) ] .
📚 References ▾
15 REFERENCES 1. Rossouw JE, et al. Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause.
JAMA . 2007;297:1465–1477. 2.
Hsia J, et al. Conjugated Equine Estrogens and Coronary Heart Disease. Arch Int Med .
2006;166:357–365. 3. Curb JD, et al.
Venous Thrombosis and Conjugated Equine Estrogen in Women Without a Uterus. Arch Int Med . 2006;166:772–780.
4. Cushman M, et al. Estrogen Plus Progestin and Risk of Venous Thrombosis.
JAMA . 2004;292:1573–1580. 5.
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. 6. Chlebowski RT, et al.
Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women. JAMA . 2003;289:3234–3253.
7. Anderson GL, et al. Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures.
JAMA . 2003;290:1739–1748. 8.
Shumaker SA, et al. Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women. JAMA.
2004;291:2947–2958. 9. 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.
10. Hendrix SL, et al. Effects of Conjugated Equine Estrogen on Stroke in the Women's Health Initiative.
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📄 Patient Package Insert ▾
PATIENT INFORMATION Conjugated estrogens tablets, USP ("kon′ju gay″ted es′troe jenz") Read this PATIENT INFORMATION before you start taking conjugated estrogens tablets and read what you get each time you refill your conjugated estrogens tablets prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT CONJUGATED ESTROGENS TABLETS (AN ESTROGEN MIXTURE)? • 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 conjugated estrogens tablets. 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 the cause. • Do not use estrogen-alone to prevent heart disease, heart attacks, or dementia (decline of brain function) • Using estrogen-alone may increase your chances of getting strokes or blood clots • Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older • Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia • Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots • Using estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older • You and your healthcare provider should talk regularly about whether you still need treatment with conjugated estrogens tablets What is conjugated estrogens tablets?
Conjugated estrogens tablets is a medicine that contains a mixture of estrogen hormones. What is conjugated estrogens tablets used for? Conjugated estrogens tablets is used after menopause to: • Reduce moderate to severe hot flushes 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 get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating ("hot flushes"). In some women the symptoms are mild, and they will not need to take estrogens. In other women, symptoms can be more severe. • Treat menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with conjugated estrogens tablets to control these problems.
If you use conjugated estrogens tablets 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. • Help reduce your chances of getting osteoporosis (thin weak bones) Osteoporosis from menopause is a thinning of the bones that makes them weaker and easier to break. If you use conjugated estrogens tablets only to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you.
Weight-bearing exercise, like walking or running, and taking calcium (1500 mg/day of elemental calcium) and vitamin D (400–800 IU/day) supplements may also lower your chances of getting postmenopausal osteoporosis. It is important to talk about exercise and supplements with your healthcare provider before starting them. You and your healthcare provider should talk regularly about whether you still need treatment with conjugated estrogens tablets.
Conjugated estrogens tablets is also used to: •Treat certai… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
0.3mg-1 0.45mg-1 0.625mg-1