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 Climara Pro are: application site reaction, vaginal bleeding, breast pain, upper respiratory infection, back pain, depression, pain, headache and flu syndrome. To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-84-BAYER (1-888-842-2937) 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 practice. The data described below is from a one-year, prospective, multicenter, double blind, double dummy, randomized, controlled trial investigating the effect of three different dosage combinations of E 2 /LNG versus E 2 alone on the development of endometrial hyperplasia. All women were postmenopausal, had a serum estradiol level of less than 20 pg/mL, and the sample included both symptomatic and asymptomatic women. The data below includes all adverse reactions reported at a frequency of >3% in the E 2 /LNG 0.045 / 0.015 group (the approved dosage for Climara Pro, N=212) and the E 2 alone group (N=204).

Table 1: All Treatment Emergent Reactions Regardless of Relationship Reported at a Frequency of >3% with Climara Pro in the 1-year Endometrial Hyperplasia Study Body System Adverse Reaction Climara Pro 0.045 / 0.015 E 2 N N = total number of subjects in a treatment group; n = number of subjects with event. = 212 N = 204 Body as a Whole Abdominal pain 9 11 Accidental injury 7 6 Back pain 13 12 Flu syndrome 10 13 Infection 7 10 Pain 11 13 Cardiovascular System Hypertension 7 9 Digestive System Flatulence 8 11 Metabolic and Nutritional Edema 8 5 Weight gain 6 10 Musculoskeletal System Arthralgia 9 10 Nervous System Depression 12 7 Headache 11 14 Respiratory System Bronchitis 9 7 Sinusitis 8 12 Upper respiratory infection 28 26 Skin and Appendages Application site reaction 86 69 Breast pain 40 20 Rash 5 10 Urogenital System Urinary Tract Infection 7 8 Vaginal Bleeding 78 44 Vaginitis 4 6 Irritation potential of Climara Pro was assessed in a 3-week irritation study. The study compared the irritation of a Climara Pro placebo patch (22 cm 2 ) to a placebo (25 cm 2 ). Visual assessments of irritation were made on Day 7 of each wear period, approximately 30 minutes after patch removal using a 7-point scale (0 = no evidence of irritation; 1 = minimal erythema, barely perceptible; 2 = definite erythema, readily visible, or minimal edema, or minimal papular response; 3–7 = erythema and papules, edema, vesicles, strong extensive reaction). The mean irritation scores were 0.13 (week 1), 0.12 (week 2), and 0.06 (week 3) for the Climara Pro. The mean scores for the placebo group were 0.2 (week 1), 0.26 (week 2), 0.12 (week 3). There were no irritation scores greater than 2 at any timepoint in any woman. In controlled clinical trials, withdrawals due to application site reactions occurred in 6 (2.1 percent) of women in the 12-week symptom study and in 71 (8.5 percent) of subjects in the 1-year endometrial protection study.

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of Climara Pro. 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. Genitourinary System Changes in bleeding patterns Gastrointestinal Abdominal distension, Combined two or more similar ARs abdominal pain, nausea Skin Alopecia, night sweats, pruritus, Rash, hot flush Central Nervous System Dizziness, headache, insomnia Miscellaneous Application site reaction, weight increased, anaphylactic reaction