Estradiol

Climara is indicated for: Climara is an estrogen indicated for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause. Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause. Limitations of Use When prescribing solely for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, first consider the use of topical vaginal products. Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure. Prevention of Postmenopausal Osteoporosis. Limitations of Use When prescribing solely for the prevention of postmenopausal osteoporosis, first consider the use of non-estrogen medications. Consider estrogen therapy only for women at significant risk of osteoporosis.

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.

Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, consider addition of a progestogen to reduce the risk of endometrial cancer. Generally, a woman without a uterus does not need to use a progestogen in addition to her estrogen therapy. In some cases, however, hysterectomized women who have a history of endometriosis may need a progestogen. Use estrogen-alone, or in combination with a progestogen at the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Reevaluate postmenopausal women periodically as clinically appropriate to determine if treatment is still necessary. Start therapy with Climara 0.025 mg per day applied to the skin once-weekly. Dosage adjustment should be guided by the clinical response.

Climara is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding Breast cancer or history of breast cancer Estrogen-dependent neoplasia Active DVT, PE, or a history of these conditions Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions Known anaphylactic reaction, or angioedema, or hypersensitivity to Climara Hepatic impairment or disease Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders Undiagnosed abnormal genital bleeding. Breast cancer or a history of breast cancer. Estrogen-dependent neoplasia. Active DVT, PE or a history of these conditions.

Boxed warning (endometrial cancer, cardiovascular disorders, probable dementia and breast cancer): 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 progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. 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 hormone replacement therapy

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders Malignant Neoplasms The most common adverse reactions (≥10 percent) with Climara are: breast pain, upper respiratory tract infections, headaches, abdominal pain, pain, and edema.

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 adverse reactions. Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.

Store at 20°C to 25°C (66°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Do not store above 86°F (30°C). Do not store unpouched.