General Information

Evamist (estradiol) is a metered dose transdermal spray formulation of estradiol. Estradiol is an endogenous estrogen largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics.

Evamist is specifically indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.

Evamist is supplied as a metered-dose pump spray designed for trans-dermal administration. The recommended initial dose of the drug is one, two or three sprays applied each morning to adjacent, non-overlapping areas on the inner surface of the forearm, starting near the elbow. Each spray contains 90 mcL which contains 1.53 mg of estradiol.

Mechanism of Action

Evamist (estradiol) is a metered-dose transdermal spray (MDTS) formulation of estradiol. Estradiol is an endogenous estrogen largely responsible for the development and maintenance of the female reproductive system and secondary sexual characteristics. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feed back mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women.

Side Effects

Adverse events associated with the use of Evamist may include, but are not limited to, the following:

• Headache
• Breast Tenderness
• Nausea
• Nasopharyngitis
• Back pain
• Nipple pain

In addition, the use of estrogen therapy has been associated with an increased risk of strokes, deep vein thrombosis, pulmonary embolism, myocardial infarction and breast cancer.

Clinical Results

FDA approval of Evamist was based on the results of one clinical trial. This 12-week, randomized, double-blind, placebo-controlled trial enrolled 454 postmenopausal women. The subjects were randomized to receive at least one dose of Evamist (one, two or three 90 mcL sprays) or placebo. The efficacy of Evamist based on a statistically significant and clinically significant (at least two per day or 14 per week difference) reduction in hot flush frequency and a statistically significant reduction in severity when compared to placebo.

The effect of treatment with Evamist on the daily frequency of moderate to severe vasomotor symptoms at week 4 and week 12 was as follows:

One Spray
At baseline mean disease severity was 11.81 for the Evamist group and 12.41 for the placebo group. At week 4 disease severity had improved to -6.26 in the Evamist group versus -3.64 in the placebo group (p-value 0.0010). At week 12 the mean disease severity score in the Evamist group was -8.10 versus -4.76 in the placebo group (p-value 0.0004).
Two Sprays
At baseline the disease severity was 12.66 in the Evamist cohort and 12.13 in the placebo cohort. At week 4 disease severity had improved to -7.30 in the Evamist cohort versus -4.74 in the placebo cohort (p-value 0.0027). At week 12 the Evamist cohort showed a mean disease severity rating of -8.66 compared to -6.19 in the placebo cohort (p-value 0.0099).
Three Sprays
At baseline the Evamist arm reported mean disease severity of 10.78 and the placebo arm reported disease severity of 12.55. At week 4 the disease severity for Evamist improved to -6.64 versus -4.54 for placebo (p-value 0.0002). At week 12 the disease severity in the Evamist arm was -8.44 compared to -5.32 in the placebo arm (p-value <0.0001).

The effect of Evamist on the weekly severity of moderate to severe vasomotor symptoms at week 4 and week 12

One Spray
At baseline mean disease severity was 2.53 for the Evamist group and 2.55 for the placebo group. At week 4 disease severity improved to -0.47 in the Evamist group compared to -0.19 in the placebo group (p-value 0.0573). At week 12 mean disease severity was -1.04 in the Evamist group versus -0.26 for placebo (p-value <0.0001).
Two Sprays
At baseline the mean disease severity was 2.54 in the Evamist cohort and 2.54 in the placebo cohort. At week 4 the mean disease severity had improved to -0.57 for Evamist and -0.25 for placebo (p-value 0.0160). At week 12 the mean disease severity was -0.92 in the Evamist cohort compared to -0.54 in the placebo cohort (p-value 0.0406).
Three Sprays
At baseline the mean disease severity was 2.58 in the Evamist arm and 2.54 in the placebo arm. At week 4 disease severity had improved to -0.43 for Evamist versus -0.13 for placebo (p-value 0.0031). At week 12 mean disease severity was -1.07 for the Evamist arm compared to -0.31 for the placebo arm (p-value <0.0001).