This grade answers one narrow question: how strong is the public evidence and safety record behind this drug, and how clean is its money trail and court record? It is not a verdict on whether the drug is right for you.
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 (...
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 1.2 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, topical vaginal products should be considered. 1.3 Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure 1.4 Treatment of Breast Cancer (for Palliation Only) in Appropriately Selected Women and Men with Metastatic Disease 1.5 Treatment of Advanced Androgen-Dependent Carcinoma of the Pr...
therapy is contraindicated in individuals with any of the following conditions: • Undiagnosed abnormal genital bleeding • Known, suspected, or history of breast cancer except in appropriately selected patients being treated for metastatic disease • Known or suspected estrogen-dependent neoplasia • Active DVT, PE, or a history of these conditions • Active arterial thromboembolic disease (for example stroke and MI), or a history of these conditions • Known anaphylactic reaction or angioedema with Premarin • Known liver impairment or disease • Known protein C, protein S or antithrombin deficiency, or other known thrombophilic disorders. • Known or suspected pregnancy • Undiagnosed abnormal genital bleeding ( 4 ) • Known, suspected, or history of breast cancer except in appropriately selected patients being treated for metastatic diseases ( 4 , 5.2 ) • Known or suspected 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 PREMARIN ( 5.7 ) • Known liver impairment or diseas...
• 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 , 5.11 , 5.12 ) • Monitor thyroid function in women on thyroid replacement therapy ( 5.13 , 5.18 ) 5.1 Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke and MI has been reported with estrogen plus progestin therapy. Should any of these 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-...
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 percent) 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 Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical 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 percent Caucasian), 1,012 women were treated with conjugated estrogens, and 332 were treated with placebo. Table 1 summarizes treatment-related adverse reactions that occ...
Warnings and Precautions, Malignant Neoplasms ( 5.2 ) 2/2024
Source: FDA SPL label for Premarin (A-S Medication Solutions), effective 20250402. Full label on DailyMed.
These are counts of reports people filed, not rates of harm. Anyone can file one, and nobody checks whether the drug was the cause. Millions of doses are taken for every report sent, so the useful part is how this drug compares with the average across all drugs.
| 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 |
|---|---|---|---|---|---|---|---|
| 2,173 | 2,311 | 1,535 | 1,414 | 1,085 | 855 | 643 | 267 |
2,876 reports blaming this drug for every million Medicare prescriptions filled, which is 1.0× the typical drug on this site. (1,756 reports in 2024–2026, against 610,592 Medicare fills in one year. This is the one number here that accounts for how many people take the drug.)
Source: the FDA's Adverse Event Reporting System (FAERS). Reports are voluntary and unverified. Drugs that are prescribed a lot, in the news, or in lawsuits attract more reports, so the percentages are compared with the whole database to correct for that partly, not fully.
| Date | Class | Firm | Reason |
|---|---|---|---|
| 09/2016 | Class III | Pfizer Inc. | Labeling: Incorrect or Missing Lot and/or Exp Date: Bottles were incorrectly labeled with an expiry date of 11/17; the correct date is 09/17. |
Class I = reasonable probability of serious harm. Class II = temporary or reversible harm. Class III = unlikely to harm. Most generic recalls are manufacturing or labeling defects for one lot, not a verdict on the molecule.
Counts measure how much evidence exists and how transparent it is, not how big the benefit is. For that, ask your prescriber: if 100 people like me took this, how many would get better because of it, and how many would be harmed? (Doctors call these the "number needed to treat" and "number needed to harm.") It differs by condition and is the number drug ads leave out. Sources: PubMed, ClinicalTrials.gov.
In 2024, drug companies reported $172,291 in payments to US physicians and hospitals tied to this drug across 9,117 transactions (Premarin $172,291).
No pending federal MDL names this drug or its brands.
Not named in any federal pharmaceutical settlement of $100M or more on record.
Sources: CMS Open Payments (Sunshine Act); Judicial Panel on Multidistrict Litigation pending docket list; DOJ settlements as tabulated on Wikipedia with links to the primary record. State-court and individual suits are not included.
1 drug in the same class grades a letter or more higher than estrogens, conjugated (usp) on this site. Worth asking whether one of them would do the same job for you.
Same ATC pharmacological class, graded ones first, best grade at the top. Being in the same class does not make them interchangeable for your condition; it makes them worth asking about.