Efficacy & Safety
Efficacy & Safety

Safety Profile

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.

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia.

The Women's Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women with daily oral conjugated estrogens (CE) alone. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women with daily oral CE combined with medroxyprogesterone acetate (MPA). In the absence of comparable data, these risks should be assumed to be similar for other dosage forms of estrogens.

The WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older, in both the estrogen alone and estrogen plus progestin arms. It is unknown whether these findings apply to younger postmenopausal women.

The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.

Estrogens with or without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

Common adverse reactions occurring in ≥2% of subjects1

** This is an optional area where footnotes can live.

Premarin Vaginal Cream therapy should not be used in women with any of the following conditions1:

  • Undiagnosed abnormal genital bleeding
  • Known, suspected, or history of breast cancer
  • 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 to Premarin Vaginal Cream
  • Known liver dysfunction or disease
  • Known protein C, protein S or antithrombin deficiency or other known thrombophilic disorders
  • Known or suspected pregnancy

In a clinical study with a 12-week, double-blind, placebo-controlled phase + a 40-week, open-label phase, there were no cases of endometrial hyperplasia or carcinoma at 1 year1

** This is an optional area where footnotes can live.

  • Endometrial safety was assessed by endometrial biopsy for all randomly assigned subjects at week 52
​​​​​​​The safety of Premarin Vaginal Cream beyond 52 weeks at any dose is not well known. The data on this page are not intended to minimize the risk of endometrial hyperplasia and associated neoplasms included as part of the WHI Black Box warning for all estrogen therapies. The decision as to whether or not to add a progestin to the unopposed estrogen in Premarin Vaginal Cream should be left up to the physician’s clinical judgment based on the individual patient’s risks.
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Study Description

Results from a 12-week, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of Premarin Vaginal Cream for the treatment of vulvovaginal atrophy in generally healthy postmenopausal women aged 44 to 77 years (N=423), 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. Premarin Vaginal Cream was administered using 2 dosing regimens: 0.5 g twice weekly and 0.5 g once daily (21 days on/7 days off). The study consisted of an initial 12-week trial followed by an open-label extension to assess endometrial safety through week 52.

​​​​​​​Primary end points were the changes from baseline in vaginal maturation index, vaginal pH, and severity of patient-reported most bothersome symptom at week 12. Participants defined the severity of their most bothersome symptom on the following scale: 1=mild, 2=moderate, 3=severe. For most women, dyspareunia was identified as the most bothersome symptom at baseline. Weekly severity score is an average of the daily scores.1,2

Efficacy & Safety

  • Efficacy
  • Safety Profile

References:
​​​​​​​
  1. Premarin Vaginal Cream [prescribing information]. New York, NY: Pfizer Inc.; 2018.
  2. Data on file. Pfizer Inc., New York, NY.

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.

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women with daily oral conjugated estrogens (CE) alone. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women with daily oral CE combined with medroxyprogesterone acetate (MPA). In the absence of comparable data, these risks should be assumed to be similar for other dosage forms of estrogens.

The WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older, in both the estrogen alone and estrogen plus progestin arms. It is unknown whether these findings apply to younger postmenopausal women.

The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.

Estrogens with or without progestins should be prescribed at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

PREMARIN VAGINAL CREAM should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (eg, stroke, myocardial infarction), or a history of these conditions; anaphylactic reaction or angioedema to Premarin Vaginal Cream; liver dysfunction or disease; thrombophilic disorders; pregnancy.

Estrogens increase the risk of gallbladder disease. Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs. Monitor thyroid function in women on thyroid replacement therapy, because estrogens may be associated with increased thyroid binding globulin (TBG) levels.

​​​​​​​In a prospective, randomized, placebo-controlled, double-blind study, the most common adverse reactions (≥2%) were headache, pelvic pain, vasodilation, breast pain, leucorrhea, metrorrhagia, vaginitis, and vulvovaginal disorder.

Premarin Vaginal Cream is indicated for the treatment of atrophic vaginitis and kraurosis vulvae; and for the treatment of moderate to severe dyspareunia, 
a symptom of vulvar and vaginal atrophy, due to menopause.

Please see Full Prescribing Information, including BOXED WARNING and Patient Information.

Indications

Premarin Vaginal Cream is indicated for the treatment of atrophic vaginitis and kraurosis vulvae; and for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.