ADVERSE REACTIONS
See BOXED WARNINGS, WARNINGS and PRECAUTIONS
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 adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Table 8: All Treatment Emergent Events Regardless of Relationship Reported at a Frequency of > 3% with Climara Pro in the 1 year Endometrial Hyperplasia Study
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Climara Pro
0.045 / 0.015
N = 212
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E2
N = 204 |
Body as a whole
|
Abdominal pain |
9 (4.2) |
11 (5.4) |
Accidental Injury |
7 (3.3) |
6 (2.9) |
Back pain |
13 (6.1) |
12 (5.9) |
Flu syndrome |
10 (4.7) |
13 (6.4) |
Infection |
7 (3.3) |
10 (4.9) |
Pain |
11 (5.2) |
13 (6.4) |
Cardiovascular
|
Hypertension |
7 (3.3) |
9 (4.4) |
Digestive |
Flatulence |
8 (3.8) |
11 (5.4) |
Metabolic and Nutritional Disorders
|
Edema |
8 (3.8) |
5 (2.5) |
Weight gain |
6 (2.8) |
10 (4.9) |
Musculoskeletal
|
Arthralgia |
9 (4.2) |
10 (4.9) |
Nervous
|
Depression |
12 (5.7) |
7 (3.4) |
Headache |
11 (5.2) |
14 (6.9) |
Respiratory
|
Bronchitis |
9 (4.2) |
7 (3.4) |
Sinusitis |
8 (3.8) |
12 (5.9) |
Upper Respiratory Infection |
28 (13.2) |
26 (12.7) |
Skin and Appendages
|
Application site reaction |
86 (40.6) |
69 (33.8) |
Breast pain |
40 (18.9) |
20 (9.8) |
Rash |
5 (2.4) |
10 (4.9) |
Urogenital
|
Urinary Tract Infection |
7 (3.3) |
8 (3.9) |
Vaginal Bleeding |
78 (36.8) |
44 (21.6) |
Vaginitis |
4 (1.9) |
6 (2.9) |
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 cm2) to a Climara placebo (25 cm2). 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 placebo. The mean scores for the Climara placebo 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 subject.
In controlled clinical trials, withdrawals due to application site reactions occurred in 6 (2.1%) of subjects in the 12-week symptom study and in 71 (8.5%) of subjects in the 1-year endometrial protection study.
The following additional adverse reactions have been reported with estrogen and/or estrogen/progestin therapy:
1. Genitourinary system
Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.
2. Breasts
Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
3. Cardiovascular
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.
4. Gastrointestinal
Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas.
5. Skin
Chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.
6. Eyes
Retinal vascular thrombosis, intolerance to contact lenses.
7. Central nervous system
Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.
8. Miscellaneous
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
OVERDOSAGE
Serious ill effects have not been reported following acute ingestion of large doses of estrogen/progestin-containing oral contraceptives by young children. Overdosage of estrogen may cause nausea and vomiting, and withdrawal bleeding may occur in females.
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