ESTROGEL

AbsorptionEstradiol is transported across intact skin and into the systemic circulation by a passive diffusion process. The rate of diffusion across the stratum corneum is the rate- limiting factor. When EstroGel is applied to the skin, it dries in 2 to 5 minutes. EstroGel 1.25 g (containing 0.75 mg of estradiol) was administered to 24 postmenopausal women once daily on the posterior surface of 1 arm from wrist to shoulder for 14 consecutive days. Mean maximal serum concentrations of estradiol ...

14.1 Effects on Vasomotor Symptoms in Postmenopausal Women In a placebo-controlled study, 145 postmenopausal women between 29 and 67 years of age (81.4 percent were White) were randomly assigned to receive 1.25 g of EstroGel (containing 0.75 mg of estradiol) or placebo gel for 12 weeks. Efficacy was assessed at 4 and 12 weeks of treatment. A statistically significant reduction in the frequency and severity of moderate to severe hot flushes was shown at Weeks 4 and 12. ( See Table 2 ) TABLE 2 Mean Change from Baseline in the Number and Severity of Hot Flushes per Day, ITT Population, LOCF Numbe...

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning , and Warnings and Precautions ( 5.1 )] Malignant Neoplasms [see Boxed Warning , and Warnings and Precautions ( 5.2 )] The most common adverse reactions with EstroGel (≥5 percent) are: headache, flatulence, and breast pain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact ASCEND Therapeutics ® US, LLC at 1-877-204-1013 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch....

EstroGel is contraindicated in women with any of the following conditions: Abnormal genital bleeding of unknown etiology [see Warning and Precautions ( 5.2 ) ]. Current or history of breast cancer [see Warning and Precautions ( 5.2 ) ]. Current or history of estrogen-dependent neoplasia [see Warning and Precautions ( 5.2 ) ]. Active DVT, PE, or history of these conditions [ see Warning and Prec...

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 ) 5.1 Cardiovascular Disorders EstroGel is contraindicated in women with active DVT, PE, stroke, or a history of these conditions [see Contraindications ( 4 ) ]. Immediately discontinue EstroGel if a PE, DVT, or stroke, o...

7 DRUG INTERACTIONS 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 re...