A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
CombiPatch Side Effects, and Drug Interactions - Estradiol/norethindrone Acetate
CombiPatch Side Effects, and Drug Interactions - Estradiol/norethindrone Acetate
SIDE EFFECTS
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®
|
CombiPatch®
|
Placebo
|
|
|
0.05/0.14 mg per day1 n = 113
|
0.05/0.25 mg per day1 n = 112
|
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®
|
CombiPatch®
|
Vivelle®
|
|
|
0.05/0.14 mg per day1 n = 325
|
0.05/0.25 mg per day1 n = 312
|
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
|
DRUG INTERACTIONS
Drug/Laboratory Test Interactions.
1. Accelerated prothrombin time, partial thromboplastin time,
and platelet aggregation time; increased platelet count; increased factors II,
VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex,
II-VII-X complex; and beta-thromboglobulin; decreased levels of anti-factor
Xa and antithrombin III; decreased antithrombin III activity; increased levels
of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.
2. Increased thyroid-binding globulin (TBG) leading to increased
circulating total thyroid hormone, as measured by protein-bound iodine (PBI),
T4 levels (by column or by radioimmunoassay) or T3 levels
by radioimmunoassay. T3 resin uptake is decreased, reflecting the
elevated TBG. Free T4 and free T3 concentrations are unaltered.
Patients on thyroid replacement therapy may require higher doses of thyroid
hormone.
3. Other binding proteins may be elevated in serum (i.e., corticosteroid
binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased
circulating corticosteroids and sex steroids, respectively. Free or biologically
active hormone concentrations are unchanged. Other plasma proteins may be increased
(angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
4. Increased plasma HDL and HDL-2 subfraction concentrations,
reduced LDL cholesterol concentration, increased triglycerides levels.
5. Impaired glucose tolerance.
6. Reduced response to metyrapone test.
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