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 IV. All Treatment Emergent Study Events Regardless of Relationship Reported at a Frequency of 5% with CombiPatch VASOMOTOR SYMPTOM STUDIES
|
|||
|
CombiPatch 0.05/0.14 mg per day1 n = 113
|
CombiPatch 0.05/0.25 mg per day1 n = 112
|
Placebo n = 107
|
|
| Body as a Whole |
46%
|
48%
|
41%
|
| Abdominal pain |
7%
|
6%
|
4%
|
| Accidental injury |
4%
|
5%
|
8%
|
| Asthenia |
8%
|
12%
|
4%
|
| Back pain |
11%
|
9%
|
5%
|
| Flu syndrome |
9%
|
5%
|
7%
|
| Headache |
18%
|
20%
|
20%
|
| Pain |
6%
|
4%
|
9%
|
| Digestive |
19%
|
23%
|
24%
|
| Diarrhea |
4%
|
5%
|
7%
|
| Dyspepsia |
1%
|
5%
|
5%
|
| Flatulence |
4%
|
5%
|
4%
|
| Nausea |
11%
|
8%
|
7%
|
| Nervous |
16%
|
28%
|
28%
|
| Depression |
3%
|
5%
|
9%
|
| Insomnia |
3%
|
6%
|
7%
|
| Nervousness |
3%
|
5%
|
1%
|
| Respiratory |
24%
|
38%
|
26%
|
| Pharyngitis |
4%
|
10%
|
2%
|
| Respiratory disorder |
7%
|
12%
|
7%
|
| Rhinitis |
7%
|
13%
|
9%
|
| Sinusitis |
4%
|
9%
|
9%
|
| Skin and Appendages |
8%
|
17%
|
16%
|
| Application site reaction |
2%
|
6%
|
4%
|
| Urogenital |
54%
|
63%
|
28%
|
| Breast pain |
25%
|
31%
|
7%
|
| Dysmenorrhea |
20%
|
21%
|
5%
|
| Leukorrhea |
5%
|
5%
|
3%
|
| Menstrual Disorder |
6%
|
12%
|
2%
|
| Papanicolaou Smear Suspicious |
8%
|
4%
|
5%
|
| Vaginitis |
6%
|
13%
|
5%
|
| 1 Represents milligrams of estradiol/NETA delivered daily by each system | |||
|
Table V. All Treatment Emergent Study Events Regardless of Relationship Reported at a Frequency of 5% with CombiPatch ENDOMETRIAL HYPERPLASIA STUDIES
|
|||
|
CombiPatch 0.05/0.14 mg per day1 n = 325
|
CombiPatch 0.05/0.25 mg per day1 n = 312
|
Vivelle 0.05 mg per day n = 318
|
|
| Body as a Whole |
61%
|
60%
|
59%
|
| Abdominal pain |
12%
|
14%
|
16%
|
| Accidental injury |
10%
|
11%
|
8%
|
| Asthenia |
10%
|
13%
|
11%
|
| Back pain |
15%
|
14%
|
13%
|
| Flu syndrome |
14%
|
10%
|
7%
|
| Headache |
25%
|
17%
|
21%
|
| Infection |
5%
|
3%
|
3%
|
| Pain |
19%
|
15%
|
13%
|
| Digestive |
42%
|
32%
|
31%
|
| Constipation |
2%
|
5%
|
3%
|
| Diarrhea |
14%
|
9%
|
7%
|
| Dyspepsia |
8%
|
6%
|
5%
|
| Flatulence |
7%
|
5%
|
6%
|
| Nausea |
8%
|
12%
|
11%
|
| Tooth Disorder |
6%
|
4%
|
1%
|
| Metabolic and Nutritional Disorders |
12%
|
13%
|
11%
|
| Peripheral edema |
6%
|
6%
|
5%
|
| Musculoskeletal |
17%
|
17%
|
15%
|
| Arthralgia |
6%
|
6%
|
5%
|
| Nervous |
33%
|
30%
|
28%
|
| Depression |
8%
|
9%
|
8%
|
| Dizziness |
6%
|
7%
|
5%
|
| Insomnia |
8%
|
6%
|
4%
|
| Nervousness |
5%
|
6%
|
3%
|
| Respiratory |
45%
|
43%
|
40%
|
| Bronchitis |
5%
|
3%
|
4%
|
| Pharyngitis |
9%
|
9%
|
8%
|
| Respiratory disorder |
13%
|
9%
|
13%
|
| Rhinitis |
19%
|
22%
|
17%
|
| Sinusitis |
10%
|
12%
|
12%
|
| Skin and Appendages |
38%
|
37%
|
31%
|
| Acne |
4%
|
5%
|
4%
|
| Application site reaction |
20%
|
23%
|
17%
|
| Rash |
6%
|
5%
|
3%
|
| Urogenital |
71%
|
79%
|
74%
|
| Breast Enlargement |
2%
|
7%
|
2%
|
| Breast pain |
34%
|
48%
|
40%
|
| Dysmenorrhea |
30%
|
31%
|
19%
|
| Leukorrhea |
10%
|
8%
|
9%
|
| Menorrhagia |
2%
|
5%
|
9%
|
| Menstrual Disorder |
17%
|
19%
|
14%
|
| Vaginal hemorrhage |
3%
|
6%
|
12%
|
| Vaginitis |
9%
|
13%
|
13%
|
| 1 Represents milligrams of estradiol/NETA delivered daily by each system | |||
The following additional adverse reactions have been reported with estrogen and/or 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, that 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/anaplylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.