Estradiol

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Estradiol gel, 0.1% is an estrogen indicated for the treatment of moderate to severe vasomotor symptoms due to menopause (1.1) . 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Dosage and administration 2 DOSAGE AND ADMINISTRATION Daily administration of 0.25 to 1.25 grams of estradiol gel, 0.1% to the right or left upper thigh on alternating days. Women should be started with the lowest effective dose and the dose should be evaluated periodically (2) . 2.1 Important Use Information The timing of estradiol gel, 0.1% initiation can affect the overall benefit-risk profile. Consider initiating estradiol gel, 0.1% in women <60 years old or <10 years since menopause onset [see Warnings and Precautions (5) , Use in Specific Populations (8.5) and Clinical Studies (14) ] . When estrogen is prescribed for a menopausal woman with a uterus, the addition of a progestogen has been shown to reduce the risk of endometrial cancer. There are possible risks associated with the use of progestogens plus estrogens that differ from those of estrogen-alone regimens. See prescribing information for progestogens indicated for the prevention of endometrial hyperplasia in non-hysterectomized menopausal women receiving estrogens [see Warnings and Precautions (5.2 , 5.3) ] . Generally, a woman without a uterus, does not need to use a progestogen with estrogen therapy. In some cases, however, hysterectomized women with a history of endometriosis may benefit from the addition of a progestogen [see Warnings and Precautions (5.13) ] . 2.2 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause Start therapy with the 0.25 grams applied once daily on the skin of either the right or left upper thigh. Adjust the dose up to a maximum of 1.25 grams, as needed. The application surface area should be about 5 by 7 inches (approximately the size of two palm prints). The entire contents of a unit dose packet should be applied each day. To avoid potential skin irritation, apply estradiol gel, 0.1% to the right or left upper thigh on alternating days. Do not apply estradiol gel, 0.1% on the face, breasts, or irritated skin or in or around the vagina. Allow gel to dry after application before dressing. Do not wash the application site within 1 hour after applying estradiol gel, 0.1%. Avoid contact of the gel with eyes. Wash hands after application. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Cardiovascular Disorders: Increased risk of PE, DVT, and stroke with estrogen-alone therapy. Discontinue if an arterial or venous thrombotic or thromboembolic event occurs. (5.1) Estrogens increase the risk of gallbladder disease (5.4) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs (5.5 , 5.6 , 5.8 , 5.9) Monitor thyroid function in women on thyroid replacement therapy (5.10 , 5.21) 5.1 Cardiovascular Disorders Estradiol gel is contraindicated in women with active DVT, PE, stroke, or a history of these conditions [see Contraindications (4) ] . Immediately discontinue estradiol gel if a PE, DVT, or stroke, occurs or is suspected. If feasible, discontinue estradiol gel at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. The safety and efficacy of estradiol gel for the prevention of cardiovascular disorders has not been established. The Women’s Health Initiate (WHI) estrogen-alone trial reported increased risks of pulmonary embolism (PE), deep vein thrombosis (DVT), and stroke, in postmenopausal women (50 to 79 years of age, average age 63.4 years) during 7.2 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] relative to placebo. Analyses were also conducted in women aged 50 to 59 years, a group of women more likely to present with onset of moderate to severe VMS compared to women of other age groups in the trial. Only daily oral 0.625 mg CE was studied in the WHI estrogen-alone trial. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events to lower CE doses, other routes of administration, or other estrogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products [see Clinical Studies (14.2) ] . Venous Thromboembolism In women aged 50 to 59 years, the WHI estrogen-alone trial reported a relative risk for PE of 1.53 (95% confidence interval [CI], 0.63, 3.75) for CE compared to placebo, with an absolute risk difference of 4 per 10,000 women-years (WYs; 10 versus 6). The relative risk for DVT was 1.66 (95% CI 0.75, 3.67) for CE compared to placebo, with a risk difference of 5 per 10,000 WYs (13 versus 8). In the overall study population of women aged 50 to 79 years, the WHI estrogen-alone trial reported a relative risk of PE of 1.35 (95% CI 0.89, 2.05) for CE compared to