Vaginal Cream indicated for:

Treatment of Atrophic Vaginitis and Kraurosis Vulvae

Treatment of Moderate to Severe Dyspareunia, a Symptom of Vulvar and Vaginal Atrophy, due to Menopause

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.

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.

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.

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.

Estrogen-Alone Therapy

• 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 

• Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.

• 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.

•  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. 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.

Estrogen Plus Progestin Therapy

• Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

•  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 

• 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. 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. 

•  Increased risk of invasive breast cancer.

Studies find that women who use hormonal therapy for menopausal symptoms have an increased risk for ovarian cancer.

Retinal vascular thrombosis has been reported in patients receiving estrogens.

In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens.

In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis.

Premarin is contraindicated in patients with:

• 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 with 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 

Estrogen therapy should be used with caution in individuals with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases.

A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

Estrogens may be poorly metabolized in patients with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued.

Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.

Estrogens may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogen-alone is prescribed.

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.

Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

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.

PREMARIN Vaginal Cream exposure has been reported to weaken latex condoms. The potential for PREMARIN Vaginal Cream to weaken and contribute to the failure of condoms, diaphragms, or cervical caps made of latex or rubber should be considered.

PREMARIN Vaginal Cream should not be used during pregnancy.

PREMARIN should not be used during lactation.

GoToSource

• Uremic bleeding. GoToSource

• Prevent or delay the onset of coronary artery disease in postmenopausal women. GoToSource

• Stress incontinence. GoToSource

• Prevention of alzheimer’s disease. GoToSource

Endometrial cancer. GoToSource

Stroke. GoToSource

Hypocalcemia (low blood calcium level). GoToSource

Cognitive impairment in women 65 years of age or older. GoToSource

Deep vein thrombosis (blood clot that forms in a vein deep inside body) and pulmonary embolism (blockage in a lung artery). GoToSource

Breast cancer. GoToSource

Myocardial infarction. GoToSource

Systemic lupus erythematosus. GoToSource

Gallbladder disease. GoToSource

New onset of asthma. GoToSource

Lawsuits filed for endometrial cancer, breast cancer, strokes, pulmonary embolism and heart attacks.