Premarin Vaginal conjugated estrogens .625 mg/g Cream — NDC 0046-0872-04 (Billing 00046-0872-04)
This is a package of Premarin Vaginal conjugated estrogens .625 mg/g Cream from Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., marketed since Nov 1978 and currently FDA-listed.
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): 007013
- GCN: 28410
- GPI-14 (Medi-Span): 55350025003710
- HICL (First Databank): 001424
- AHFS class code: 68:16.04.00
- RxCUI (RxNorm): 688240
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 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 vaginal may be used to treat the following, depending on the specific product being prescribed: vaginal dryness, itching, and burning; painful or difficult urination; and sudden need to urinate immediately in women who are experiencing or have experienced menopause (change of life; the end of monthly menstrual periods). hot flushes ('hot flashes'; sudden strong feelings of heat and sweating) in women who are experiencing or have experienced menopause (change of life; the end of monthly menstrual periods). kraurosis vulvae (a condition that may cause vaginal dryness and discomfort...
Read the full MedlinePlus article ↗Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Conjugated Estrogens — tap one for details:
Conjugated Estrogens may be associated with lower levels of 5 nutrients — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 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 g | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $15.20 | $60.79 / 4 g |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 2, 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 |
|---|---|---|---|---|---|---|
| 00046-0872-04 You're viewing this | 1 TUBE, WITH APPLICATOR in 1 CARTON / 4 g in 1 TUBE, WITH APPLICATOR | — | — | 1978-11-01 | — | Active |
| 00046-0872-21 0046-0872-21 Main listing | 1 TUBE, WITH APPLICATOR in 1 CARTON / 30 g in 1 TUBE, WITH APPLICATOR | $15.07 / g | $452.23 | 1978-11-01 | — | Active |
This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Premarin Vaginal conjugated estrogens .625 mg/g Cream?
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 |
|---|---|---|---|---|---|---|
| Premarin Vaginal .625 mg/gthis 00046-0872-04 | Wyeth | 1 tube | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 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 1, 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
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 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 (5.3) ] .
Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.2 , 5.4) , and Clinical Studies (14.2 , 14.3) ] . 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 (5.2) , and Clinical Studies (14.2) ].
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 (5.4) , Use in Specific Populations (8.5) , and Clinical Studies (14.3) ] . 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 (5.2 , 5.4) , and Clinical Studies (14.2 , 14.3) ] . 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 (5.2) , and Clinical Studies (14.2) ] .
The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions (5.4) , Use in Specific Populations (8.5) , and Clinical Studies (14.3) ] . Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions (5.3 ), and Clinical Studies (14.2) ] .
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. 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. 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 ( 5.3 ) • Estrogen-alone therapy should not be used… [Excerpted — this section continues on DailyMed.]
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE PREMARIN (conjugated estrogens) vaginal cream is a mixture of estrogens indicated for: • Treatment of Atrophic Vaginitis and Kraurosis Vulvae ( 1.1 ) • Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause ( 1.2 )
1.1 Treatment of Atrophic Vaginitis and Kraurosis Vulvae
1.2Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer [see Boxed Warning ]. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.3 , 5.15) ] .
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. • Cyclic administration of 0.5 to 2 g intravaginally [daily for 21 days then off for 7 days] for Treatment of Atrophic Vaginitis and Kraurosis Vulvae ( 2.1 ) • Cyclic administration of 0.5 g intravaginally [daily for 21 days then off for 7 days] for Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause ( 2.2 ) • Twice-weekly administration of 0.5 g intravaginally [for example, Monday and Thursday] for Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause ( 2.2 )
2.1Treatment of Atrophic Vaginitis and Kraurosis Vulvae PREMARIN vaginal cream is administered intravaginally in a cyclic regimen (daily for 21 days and then off for 7 days). Generally, women should be started at the 0.5 g dosage strength. Dosage adjustments (0.5 to 2 g) may be made based on individual response [see Dosage Forms and Strengths (3) ] .
2.2Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause PREMARIN vaginal cream (0.5 g) is administered intravaginally in a twice-weekly (for example, Monday and Thursday) continuous regimen or in a cyclic regimen of 21 days of therapy followed by 7 days off of therapy [see Dosage Forms and Strengths (3) ] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Each gram contains 0.625 mg conjugated estrogens, USP. Combination package: Each contains a net wt. 1.06 oz (30 g) tube with plastic applicator(s) calibrated in 0.5 g increments to a maximum of 2 g. • Each gram contains 0.625 mg conjugated estrogens ( 3 ) • Combination package: Each contains a net wt. 1.06 oz (30 g) tube with plastic applicator(s) calibrated in 0.5 g increments to a maximum of 2 g ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS PREMARIN vaginal cream is contraindicated in women with any of the following conditions: • Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.3) ] • Breast cancer or a history of breast cancer [see Warnings and Precautions (5.3) ] • Estrogen-dependent neoplasia [see Warnings and Precautions (5.3) ] • Active DVT, PE, or a history of these conditions [see Warnings and Precautions (5.2) ] • Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions [see Warnings and Precautions (5.2) ] • Known anaphylactic reaction or angioedema to PREMARIN [see Warnings and Precautions (5.16, 5.17) ] • 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 , 5.3 ) • Breast cancer or a history of breast cancer ( 4 , 5.3 ) • Estrogen-dependent neoplasia ( 4 , 5.3 ) • Active DVT, PE, or a history of these conditions ( 4 , 5.2 ) • Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions ( 4 , 5.2 ) • Known anaphylactic reaction or angioedema to PREMARIN vaginal cream ( 4 , 5.16 , 5.17 ) • 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 ( 5.5 ) • Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.6 , 5.7 , 5.10 , 5.11 ) • Monitor thyroid function in women on thyroid replacement therapy ( 5.12 , 5.21 )
5.1Risks from Systemic Absorption Systemic absorption occurs with the use of PREMARIN vaginal cream. The warnings, precautions, and adverse reactions associated with oral PREMARIN treatment should be taken into account.
5.2Cardiovascular 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 history 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 (14.2) ]. 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 (14.2) ] . 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 (14.2) ] . 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 (14.2) ]. 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… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: • Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.2) ] • Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.3) ] In a prospective, randomized, placebo-controlled, double-blind study, the most common adverse reactions ≥ 2% are headache, pelvic pain, vasodilation, breast pain, leucorrhea, metrorrhagia, vaginitis, vulvovaginal disorder ( 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 .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a 12-week, randomized, double-blind, placebo-controlled trial of PREMARIN vaginal cream (PVC), a total of 423 postmenopausal women received at least 1 dose of study medication and were included in all safety analyses: 143 women in the PVC-21/7 treatment group (0.5 g PVC daily for 21 days, then 7 days off), 72 women in the matching placebo treatment group; 140 women in the PVC-2x/wk treatment group (0.5 g PVC twice weekly), 68 women in the matching placebo treatment group.
A 40-week, open-label extension followed, in which a total of 394 women received treatment with PVC, including those subjects randomized at baseline to placebo. In this study, the most common adverse reactions ≥ 1% in the double blind phase are shown below (Table 1) [see Clinical Studies (14.1) ] . Table 1: Number (%) of Patients Reporting Treatment Emergent Adverse Reactions ≥ 1% Only Treatment Body System Body system totals are not necessarily the sum of individual adverse events, since a patient may report two or more different adverse reactions in the same body system. /Adverse Reaction PVC 21/7 N=143 Placebo 21/7 N=72 PVC 2×/week N=140 Placebo 2×/week N=68 Number (%) of Patients with Adverse Reaction Body As A Whole Abdominal Pain 1 (0.7) 1 (1.4) 0 1 (1.5) Headache 5 (3.5) 1 (1.4) 3 (2.1) 1 (1.5) Moniliasis 2 (1.4) 1 (1.4) 1 (0.7) 0 Pain 2 (1.4) 0 1 (0.7) 0 Pelvic Pain 4 (2.8) 2 (2.8) 4 (2.9) 0 Cardiovascular System Migraine 0 0 0 1 (1.5) Vasodilation 3 (2.1) 2 (2.8) 2 (1.4) 0 Musculoskeletal System Muscle Cramp 2 (1.4) 0 0 0 Nervous System Dizziness 1 (0.7) 0 0 1 (1.5) Skin and Appendages Acne 0 0 2 (1.4) 0 Erythema 0 1 (1.4) 0 0 Pruritus 2 (1.4) 1 (1.4) 1 (0.7) 0 Urogenital System Breast Enlargement 1 (0.7) 1 (1.4) 0 0 Breast Pain 7 (4.9) 0 3 (2.1) 0 Dysuria 2 (1.4) 0 0 0 Leukorrhea 3 (2.1) 1 (1.4) 4 (2.9) 5 (7.4) Metrorrhagia 0 0 0 2 (2.9) Urinary Frequency 0 1 (1.4) 0 0 Urinary Tract Infection 0 1 (1.4) 0 0 Urinary Urgency 1 (0.7) 1 (1.4) 0 0 Vaginal Hemorrhage 2 (1.4) 0 1 (0.7) 1 (1.5) Vaginal Moniliasis 2 (1.4) 0 0 0 Vaginitis 2 (1.4) 1 (1.4) 3 (2.1) 3 (4.4) Vulvovaginal Disorder 4 (2.8) 0 3 (2.1) 2 (2.9)
6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of PREMARIN vaginal cream. 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 Abnormal uterine bleeding or spotting, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis (including vaginal candidiasis), change in cervical secretion, cystitis-like syndrome, application site reactions of vulvovaginal discomfort, (including burning, irritation, and genital pruritus), endometrial hyperplasia, endometrial cancer, precocious puberty, leukorrhea.
Breasts Tenderness, enlargement, pain, discharge, fibrocystic breast changes, breast cancer, gynecomastia in males. Cardiovascular Deep venous thrombosis, pulmonary embolism, myocardial infarction, stroke, increase i… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug interaction studies have been conducted for PREMARIN vaginal cream. 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 ▾
5.21Drug-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) leading to increased circulating total thyroid hormone, 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. Women 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 ( 5.4 , 8.5 )
8.1Pregnancy Risk Summary PREMARIN vaginal cream is not indicated for use during pregnancy. There are no data with the use of PREMARIN vaginal cream 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 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 developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for PREMARIN vaginal cream and any potential adverse effects on the breast-fed child from PREMARIN vaginal cream or from the underlying maternal condition.
8.4Pediatric Use PREMARIN vaginal cream is not indicated in children. Clinical studies have not been conducted in the pediatric population.
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing PREMARIN vaginal cream to determine whether those over 65 years of age differ from younger subjects in their response to PREMARIN vaginal cream. 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 (5.2) , and Clinical Studies (14.2) ] .
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 (5.2 , 5.3) , and Clinical Studies (14.2) ] . 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 (5.4) , and Clinical Studies (14.3) ] .
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 (5.4) , and Clinical Studies (14.3) ] .
8.6Renal Impairment The effect of renal impairment on the pharmacokinetics of PREMARIN vaginal cream has not been studied.
8.7Hepatic Impairment The effect of hepatic impairment on the pharmacokinetics of PREMARIN vaginal cream has not been studied.
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary PREMARIN vaginal cream is not indicated for use during pregnancy. There are no data with the use of PREMARIN vaginal cream 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 PREMARIN vaginal cream is not indicated in children. Clinical studies have not been conducted in the pediatric population.
🧓 Geriatric Use ▾
8.5Geriatric Use There have not been sufficient numbers of geriatric women involved in clinical studies utilizing PREMARIN vaginal cream to determine whether those over 65 years of age differ from younger subjects in their response to PREMARIN vaginal cream. 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 (5.2) , and Clinical Studies (14.2) ] .
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 (5.2 , 5.3) , and Clinical Studies (14.2) ] . 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 (5.4) , and Clinical Studies (14.3) ] .
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 (5.4) , and Clinical Studies (14.3) ] .
🆘 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 PREMARIN 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, which is 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 Currently, there are no pharmacodynamic data known for PREMARIN vaginal cream.
12.3Pharmacokinetics Absorption Conjugated estrogens are water soluble and are well-absorbed through the skin, mucous membranes, and the gastrointestinal (GI) tract. The vaginal delivery of estrogens circumvents first-pass metabolism. A bioavailability study was conducted in 24 postmenopausal women with atrophic vaginitis.
The mean (SD) pharmacokinetic parameters for unconjugated estrone, unconjugated estradiol, total estrone, total estradiol and total equilin following 7 once-daily doses of PREMARIN vaginal cream 0.5 g is shown in Table 2. Table 2: Mean ± SD Pharmacokinetic Parameters of PREMARIN Following Daily Administration (7 Days) of PREMARIN Vaginal Cream 0.5 g in 24 Postmenopausal Women Pharmacokinetic Profiles of Unconjugated Estrogens PREMARIN Vaginal Cream 0.5 g PK Parameters Arithmetic Mean ± SD C max (pg/mL) T max (hr) AUC ss (pg•hr/mL) Estrone 42.0 ± 13.9 7.4 ± 6.2 826 ± 295 Baseline-adjusted estrone 21.9 ± 13.1 7.4 ± 6.2 365 ± 255 Estradiol 12.8 ± 16.6 8.5 ± 6.2 231 ± 285 Baseline-adjusted estradiol 9.14 ± 14.7 8.5 ± 6.2 161 ± 252 Pharmacokinetic Profiles of CE PREMARIN Vaginal Cream 0.5 g PK Parameters Arithmetic Mean ± SD C max (ng/mL) T max (hr) AUC ss (ng•hr/mL) Total estrone 0.60 ± 0.32 6.0 ± 4.0 9.75 ±
4.99Baseline-adjusted total estrone 0.40 ± 0.28 6.0 ± 4.0 5.79 ±
3.7Total estradiol 0.04 ± 0.04 7.7 ± 5.9 0.70 ±
0.42Baseline-adjusted total estradiol 0.04 ± 0.04 7.7 ± 6.0 0.49 ±
0.38Total equilin 0.12 ± 0.15 6.1 ± 4.7 3.09 ±
1.37Distribution 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 exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation o… [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, which is 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 PREMARIN vaginal cream—Each gram contains 0.625 mg conjugated estrogens, USP. Combination package: Each contains a net wt. of 1.06 oz (30 g) tube with plastic applicator(s) calibrated in 0.5 g increments to a maximum of 2 g (NDC 0046-0872-21).
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].
📦 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].
📋 Description ▾
11 DESCRIPTION Each gram of PREMARIN (CE) vaginal cream contains 0.625 mg CE, USP in a nonliquefying base containing cetyl esters wax, cetyl alcohol, white wax, glyceryl monostearate, propylene glycol monostearate, methyl stearate, benzyl alcohol, sodium lauryl sulfate, glycerin, and mineral oil. PREMARIN vaginal cream is applied intravaginally. PREMARIN vaginal cream contains a mixture of CE obtained exclusively from natural sources, occurring as 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 as concomitant components, sodium sulfate conjugates, 17 α-dihydroequilin, 17 α-estradiol, and 17 β-dihydroequilin.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient 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 (5.3) ] .
17.2Possible Serious Adverse Reactions with Estrogens Inform postmenopausal women of possible serious adverse reactions of estrogen-alone therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.2 , 5.3 , 5.4) ] .
17.3Possible Less Serious but Common Adverse Reactions with Estrogens 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. This product’s labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com .
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption Conjugated estrogens are water soluble and are well-absorbed through the skin, mucous membranes, and the gastrointestinal (GI) tract. The vaginal delivery of estrogens circumvents first-pass metabolism. A bioavailability study was conducted in 24 postmenopausal women with atrophic vaginitis.
The mean (SD) pharmacokinetic parameters for unconjugated estrone, unconjugated estradiol, total estrone, total estradiol and total equilin following 7 once-daily doses of PREMARIN vaginal cream 0.5 g is shown in Table 2. Table 2: Mean ± SD Pharmacokinetic Parameters of PREMARIN Following Daily Administration (7 Days) of PREMARIN Vaginal Cream 0.5 g in 24 Postmenopausal Women Pharmacokinetic Profiles of Unconjugated Estrogens PREMARIN Vaginal Cream 0.5 g PK Parameters Arithmetic Mean ± SD C max (pg/mL) T max (hr) AUC ss (pg•hr/mL) Estrone 42.0 ± 13.9 7.4 ± 6.2 826 ± 295 Baseline-adjusted estrone 21.9 ± 13.1 7.4 ± 6.2 365 ± 255 Estradiol 12.8 ± 16.6 8.5 ± 6.2 231 ± 285 Baseline-adjusted estradiol 9.14 ± 14.7 8.5 ± 6.2 161 ± 252 Pharmacokinetic Profiles of CE PREMARIN Vaginal Cream 0.5 g PK Parameters Arithmetic Mean ± SD C max (ng/mL) T max (hr) AUC ss (ng•hr/mL) Total estrone 0.60 ± 0.32 6.0 ± 4.0 9.75 ±
4.99Baseline-adjusted total estrone 0.40 ± 0.28 6.0 ± 4.0 5.79 ±
3.7Total estradiol 0.04 ± 0.04 7.7 ± 5.9 0.70 ±
0.42Baseline-adjusted total estradiol 0.04 ± 0.04 7.7 ± 6.0 0.49 ±
0.38Total equilin 0.12 ± 0.15 6.1 ± 4.7 3.09 ±
1.37Distribution 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 exist 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 in specific populations, including patients with renal or hepatic impairment.
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Currently, there are no pharmacodynamic data known for PREMARIN vaginal cream.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Effects on Vulvar and Vaginal Atrophy A 12-week, prospective, randomized, double-blind placebo-controlled study was conducted to compare the safety and efficacy of 2 PREMARIN vaginal cream (PVC) regimens 0.5 g (0.3 mg CE) administered twice weekly and 0.5 g (0.3 mg CE) administered sequentially for 21 days on drug followed by 7 days off drug to matching placebo regimens in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. The initial 12-week, double-blind, placebo-controlled phase was followed by an open-label phase to assess endometrial safety through week 52.
The study randomized 423 generally healthy postmenopausal women between 44 to 77 years of age (mean 57.8 years), who at baseline had ≤ 5% superficial cells on a vaginal smear, a vaginal pH ≥ 5.0, and who identified a most bothersome moderate to severe symptom of vulvar and vaginal atrophy. The majority (92.2%) of the women were Caucasian (n = 390); 7.8% were Other (n = 33). All subjects were assessed for improvement in the mean change from baseline to Week 12 for the co-primary efficacy variables of: most bothersome symptom of vulvar and vaginal atrophy (defined as the moderate to severe symptom that had been identified by the woman as most bothersome to her at baseline); percentage of vaginal superficial cells and percentage of vaginal parabasal cells; and vaginal pH.
In the 12-week, double-blind phase, a statistically significant mean change between baseline and Week 12 in the symptom of dyspareunia was observed for both of the PREMARIN vaginal cream regimens (0.5 g daily for 21 days, then 7 days off and 0.5 g twice weekly) compared to matching placebo, see Table 3 . Also demonstrated for each PREMARIN vaginal cream regimen compared to placebo was a statistically significant increase in the percentage of superficial cells at Week 12 (28%, 21/7 regimen and 26%, twice a week compared to 3% and 1% for matching placebo), a statistically significant decrease in parabasal cells (-61%, 21/7 regimen and -58%, twice a week compared to -21% and -7% for matching placebo) and statistically significant mean reduction between baseline and Week 12 in vaginal pH (-1.62, 21/7 regimen and -1.57, twice a week compared to -0.36 and -0.26 for matching placebo).
Endometrial safety was assessed by endometrial biopsy for all randomly assigned subjects at week 52. For the 155 subjects (83 on the 21/7 regimen, 72 on the twice-weekly regimen) completing the 52-week period with complete follow-up and evaluable endometrial biopsies, there were no reports of endometrial hyperplasia or endometrial carcinoma. Table 3: Mean Change in Dyspareunia Severity Compared to Placebo MITT Population of Most Bothersome Symptom Score for Dyspareunia, LOCF Dyspareunia PVC 0.5 g 21/7 PVC 21/7 = apply PVC for 21 days and then 7 days of no therapy Placebo 0.5 g 21/7 PVC 0.5 g 2×/wk PVC 2×/wk = apply PVC twice a week Placebo 0.5 g 2×/wk Baseline n Mean (SD) 50 2.26 (0.99) n Mean (SD) 18 2.32 (0.88) n Mean (SD) 52 2.43 (0.76) n Mean (SD) 22 2.28 (1.04) Week 12 50 0.77 (1.05) 18 1.93 (1.03) 52 0.88 (0.96) 21 1.63 (1.16) Change from Baseline at Week 12 50 -1.48 (1.17) 18 -0.40 (1.01) 52 -1.55 (0.92) 21 -0.62 (1.23) P-value vs.
Placebo <0.001 Comparison of PVC 21/7 with placebo 21/7 -- <0.001 Comparison of PVC 2×/wk with placebo 2×/wk --
14.2Women'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 can… [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 (5.3) ].
📄 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 (5.3) ].
📚 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.
Circulation . 2006;113:2425–2434.
📄 Patient Package Insert ▾
PATIENT INFORMATION PREMARIN ® (prem-uh-rin) (Conjugated estrogens) vaginal cream Read this PATIENT INFORMATION before you start using PREMARIN vaginal cream and read what you get each time you refill your PREMARIN vaginal cream prescription. 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 PREMARIN vaginal cream (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 PREMARIN vaginal cream. 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 or blood clots • Using estrogen-alone may increase your chance of getting dementia, based on a study of women of 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 age 65 years of age or older • You and your healthcare provider should talk regularly about whether you still need treatment with PREMARIN vaginal cream What is PREMARIN vaginal cream?
PREMARIN vaginal cream is a medicine that contains a mixture of estrogen hormones. What is PREMARIN vaginal cream used for? PREMARIN vaginal cream is used after menopause to: • Treat menopausal changes in and around the vagina You and your healthcare provider should talk regularly about whether you still need treatment with PREMARIN vaginal cream to control these problems. • Treat painful intercourse caused by menopausal changes of the vagina Who should not use PREMARIN vaginal cream?
Do not start using PREMARIN vaginal cream if you: • Have unusual vaginal bleeding • Currently have or have had certain cancers Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use PREMARIN vaginal cream. • Had a stroke or heart attack • Currently have or have had blood clots • Currently have or have had liver problems • Have been diagnosed with a bleeding disorder • Are allergic to PREMARIN vaginal cream or any of its ingredients See the end of this leaflet for a list of ingredients in PREMARIN vaginal cream.
Tell your healthcare provider: • 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. • About all of your medical problems 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, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood. • About all the medicines you take This includes prescription and nonprescription medicines, vitamins, and herbal supplements.
Some medicines may affect how PREMARIN vaginal cream works. PREMARIN vaginal cream may also affect how your other medicines work. • If you are going to have surgery or will be on bedrest You may need to stop using PREMARIN vaginal cream. • If you are pregnant or think you may be pregnant PREMARIN vaginal cream is not for pregnant women • If you are breast feeding The hormones in PREMARIN vaginal cream can pass into your breast milk. How should… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 30 g Tube Label NDC 0046-0872-21 Premarin ® (conjugated estrogens) vaginal cream 0.625 mg/g Rx only Net Wt. 1.06 oz. (30 g) PRINCIPAL DISPLAY PANEL - 30 g Tube Label
PRINCIPAL DISPLAY PANEL - 30 g Tube Carton NDC 0046-0872-21 Premarin ® (conjugated estrogens) vaginal cream 0.625 mg/g Rx only Pfizer Net Wt. 1.06 oz. (30 g) This product also contains cetyl esters wax, cetyl alcohol, white wax, glyceryl monostearate, propylene glycol monostearate, methyl stearate, benzyl alcohol, sodium lauryl sulfate, glycerin, and mineral oil.
2 Applicators enclosed For vaginal use only. Usual Dosage: See accompanying information. PRINCIPAL DISPLAY PANEL - 30 g Tube Carton
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| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
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