EVAMIST

AbsorptionIn a multiple-dose study, 72 postmenopausal women were treated for 14 days with Evamist to the inner forearm. Serum concentrations of estradiol appeared to reach steady state after 7 to 8 days of application of one, two, or three 90 mcL sprays of Evamist per day (Figure 1). Figure 1. Mean (±SD) Serum Estradiol Concentrations on Day 14 Following Topical Application for 14 Days of One, Two or Three Sprays of Evamist (Unadjusted for Baseline) Pharmacokinetics parameters for estradiol fro...

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In a 12-week, randomized, placebo-controlled trial of Evamist in 454 women, 80 to 90 percent of women randomized to active drug received at least 70 days of therapy and 75 to 85 percent randomized to placebo received at least 70 days of therapy. The adverse reactions that occurred in at least 5 ...

The following serious adverse reactions are discussed elsewhere in the labeling:

• Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions ( 5.1 )]
• Malignant Neoplasms [see Boxed Warning, Warnings and Precautions ( 5.2 )] The most common adverse reactions (≥ 5 percent) with Evamist are: headache, breast tenderness and nipple pain, nausea, back pain, and nasopharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or ...

Evamist is contraindicated in women with any of the following conditions:

• Undiagnosed abnormal genital bleeding [see Warnings and Precautions ( 5.2 )].
• Breast cancer or a history of breast cancer [see Warnings and Precautions ( 5.2 )].
• Estrogen-dependent neoplasia [see Warnings and Precautions ( 5.2 )].
• Active DVT, PE, or history of these conditions [see Warnings and Precautions ( 5.1 )]. ...

• Estrogens increase the risk of gallbladder disease ( 5.5 )
• Discontinue estrogens if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.6 , 5.7 , 5.10 , 5.11 )
• Monitor thyroid function in women on thyroid hormone replacement therapy ( 5.12 , 5.21 ) 5.1 Cardiovascular Disorders Increased risks of stroke and DVT are reported with estrogen-alone therapy. Increased risks of PE, DVT, stroke, and MI are reported with estrogen plus progestin therap...

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 result...