Estradiolside effects

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

Cardiovascular Disorders

Malignant Neoplasms The most common adverse reactions (≥ 5 percent) with Evamist are: headache, breast tenderness and nipple pain, nausea, back pain, and nasopharyngitis. To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 percent of women in any treatment group are shown in Table 1. Table 1. Frequency of Adverse Reactions (≥5%) in Any Treatment Group in a Controlled Study of Evamist Frequency n (%) System Organ Class Preferred Term 1 Spray 2 Sprays 3 Sprays Placebo (N = 77) Evamist (N = 76) Placebo (N = 76) Evamist (N = 74) Placebo (N = 75) Evamist (N = 76) Reproductive System and Breast Disorders Breast tenderness 0 4 4 5 0 4 Nipple pain 0 2 0 5 0 1 Gastrointestinal Disorders Nausea 5 1 1 2 4 2 Infections and Infestations Nasopharyngitis 1 4 2 3 1 1 Musculoskeletal and Connective Tissue Disorders Back pain 1 2 2 4 1 2 Arthralgia 1 1 4 1 0 3 Nervous system Headache 4 7 5 9 7 8 Application site reactions were reported in 3 out of 226 (1.3%) women treated with Evamist.

6.2 Postmarketing

Experience The following additional adverse reactions have been identified during post-approval use of Evamist. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Breasts: Breast swelling, breast mass, breast enlargement Cardiovascular: Heart rate increased Central nervous system: Dizziness, dysgeusia, paresthesia, lethargy, hypoesthesia Eyes: Eye irritation, ocular hyperemia Gastrointestinal: Abdominal pain, diarrhea, constipation, abdominal distension, dry mouth, decreased appetite Genitourinary system: Vaginal bleeding Musculoskeletal: Muscle spasms, arthritis Psychiatric: Insomnia, mood swings, anxiety, irritability, mood altered, depression Respiratory tract: Cough, dyspnea, dry throat Skin: Nipple and areola discoloration, usually on the same side of the body as the inner forearm on which Evamist is applied, rash, pruritus, alopecia, urticaria, dry skin, skin discoloration, chloasma Miscellaneous: Weight increased, malaise, fatigue, asthenia