Savings & Resources | Menopause Hormone Therapies (MHT) by Pfizer for HCPs

Important Safety Information

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen or using Duavee, which contains bazedoxifene, an estrogen antagonist in the uterus has been shown to reduce the risk of endometrial hyperplasia that can occur with estrogens, and which may be a precursor to endometrial cancer. Women taking DUAVEE should not be taking progestins, additional estrogens, or additional estrogen agonist/antagonists.

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.

Estrogen therapy 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 during 7.1 years of treatment with daily oral conjugated estrogens (CE) 0.625mg alone, relative to placebo. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women during 5.6 years of treatment with daily oral CE 0.625mg combined with medroxyprogesterone acetate (MPA) 2.5mg, relative to placebo. Estrogen agonist/antagonists, including bazedoxifene, are also known to increase the risk of VTE. Should any of these occur or be suspected, PREMARIN, PREMARIN Vaginal Cream, ESTRING, or DUAVEE should be discontinued immediately.

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.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE or CE and MPA, and other dosage forms of estrogens or combinations and dosage forms of estrogens and progestins.

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, PREMARIN Vaginal Cream, ESTRING, and DUAVEE should not be used in women with any of the following conditions: undiagnosed abnormal uterine or genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active or history of venous or arterial thromboembolic disease (eg, stroke, myocardial infarction); anaphylactic reaction, angioedema, or hypersensitivity to PREMARIN, PREMARIN Vaginal Cream, ESTRING, DUAVEE, or any of their ingredients; liver impairment or disease; thrombophilic disorders; pregnancy.

Premarin, Premarin Vaginal Cream, and Estring should not be used during lactation. Duavee is not indicated for use in females of reproductive potential.

In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily conjugated estrogen (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80).

Observational studies have reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen-alone therapy. Extension of the WHI trials also demonstrated increased breast cancer risk associated with estrogen plus progestin therapy.

The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms, requiring further evaluation. The effect of treatment with DUAVEE on the risk of breast cancer is unknown.

The WHI estrogen plus progestin sub-study reported a statistically non-significant increased risk of ovarian cancer. A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown. The effect of treatment with DUAVEE on the risk of ovarian cancer is unknown.

Estrogens increase the risk of gallbladder disease. Discontinue estrogen if severe hypercalcemia, 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.

DUAVEE is not recommended for use in patients with renal impairment.

The most common adverse reactions in:

DUAVEE (≥ 5%): muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain.
PREMARIN (≥ 5%): asthenia, flatulence, depression, insomnia, endometrial hyperplasia, leucorrhea, vaginal hemorrhage, and vaginitis.
PREMARIN Vaginal Cream (≥ 2%): were vasodilation, leucorrhea, metrorrhagia, vaginitis, and vulvovaginal disorder.
ESTRING (≥ 5%): were leukorrhea, genital moniliasis, upper respiratory tract infection, and vaginitis.

IndicationS

(Duavee,Premarin Tablets,Premarin Vaginal Cream, Estring)

Duavee is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus:

Treatment of moderate-to-severe vasomotor symptoms associated with menopause
Prevention of postmenopausal osteoporosis

Limitations of Use:

Duavee should be used 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.
When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.

Premarin Tablets are indicated for:

Treatment of moderate-to-severe vasomotor symptoms due to menopause
Treatment of moderate to severe vulvar and vaginal atrophy due to menopause
Prevention of postmenopausal osteoporosis.

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.
When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.

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.

Estring is indicated for the treatment of moderate-to-severe symptoms of vulvar and vaginal atrophy due to menopause.

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