ADVERSE REACTIONS
See BOX 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.
In a 12-week clinical trial that included 72 women treated with 0.625 mg and 2 x 0.625 mg Cenestin and 48 women treated with placebo, adverse events that occurred at a rate of >/= 5% are summarized in Table 5.
Table 5 Number (%) of Patients with Adverse Events With >/=5% Occurrence Rate By Body System and Treatment Group
Body System Adverse Event |
Cenestin *
0.625 mg and
2 × 0.625 mg n (%) |
Placebo n (%) |
Total n (%) |
Number of Patients Who Received Medication
|
72
|
(100) |
48
|
(100) |
120
|
(100) |
Number of Patients With Adverse Events
|
68
|
(94) |
43
|
(90) |
111
|
(93) |
Number of Patients Without Any Adverse Events
|
4
|
(6) |
5
|
(10) |
9
|
(8) |
Body As A Whole |
Abdominal Pain
|
20
|
(28) |
11
|
(23) |
31
|
(26) |
Asthenia
|
24
|
(33) |
20
|
(42) |
44
|
(37) |
Back Pain
|
10
|
(14) |
6
|
(13) |
16
|
(13) |
Fever
|
1
|
(1) |
3
|
(6) |
4
|
(3) |
Headache
|
49
|
(68) |
32
|
(67) |
81
|
(68) |
Infection
|
10
|
(14) |
5
|
(10) |
15
|
(13) |
Pain
|
8
|
(11) |
9
|
(19) |
17
|
(14) |
Cardiovascular System |
Palpitation
|
15
|
(21) |
13
|
(27) |
28
|
(23) |
Digestive System |
Constipation
|
4
|
(6) |
2
|
(4) |
6
|
(5) |
Diarrhea
|
4
|
(6) |
0
|
(0) |
4
|
(3) |
Dyspepsia
|
7
|
(10) |
3
|
(6) |
10
|
(8) |
Flatulence
|
21
|
(29) |
14
|
(29) |
35
|
(29) |
Nausea
|
13
|
(18) |
9
|
(19) |
22
|
(18) |
Vomiting
|
5
|
(7) |
1
|
(2) |
6
|
(5) |
Metabolic and Nutritional |
Peripheral Edema
|
7
|
(10) |
6
|
(13) |
13
|
(11) |
Musculoskeletal System |
Arthralgia
|
18
|
(25) |
13
|
(27) |
31
|
(26) |
Myalgia
|
20
|
(28) |
15
|
(31) |
35
|
(29) |
Nervous System |
Depression
|
20
|
(28) |
18
|
(38) |
38
|
(32) |
Dizziness
|
8
|
(11) |
5
|
(10) |
13
|
(11) |
Hypertonia
|
4
|
(6) |
0
|
(0) |
4
|
(3) |
Insomnia
|
30
|
(42) |
23
|
(48) |
53
|
(44) |
Leg Cramps
|
7
|
(10) |
3
|
(6) |
10
|
(8) |
Nervousness
|
20
|
(28) |
20
|
(42) |
40
|
(33) |
Paresthesia
|
24
|
(33) |
15
|
(31) |
39
|
(33) |
Vertigo
|
12
|
(17) |
12
|
(25) |
24
|
(20) |
Respiratory System |
Cough Increased
|
4
|
(6) |
1
|
(2) |
5
|
(4) |
Pharyngitis
|
6
|
(8) |
4
|
(8) |
10
|
(8) |
Rhinitis
|
6
|
(8) |
7
|
(15) |
13
|
(11) |
Skin and Appendages |
Rash
|
3
|
(4) |
3
|
(6) |
6
|
(5) |
Urogenital System |
Breast Pain
|
21
|
(29) |
7
|
(15) |
28
|
(23) |
Dysmenorrhea
|
4
|
(6) |
3
|
(6) |
7
|
(6) |
Metrorrhagia
|
10
|
(14) |
3
|
(6) |
13
|
(11) |
*Combined results for 0.625 mg and 2 × 0.625 mg Cenestin Tablets
|
|
In a second 12-week clinical trial that included 52 women treated with 0.45 mg Cenestin and 51 women treated with placebo, adverse events that occurred at a rate of >5% are summarized in Table 6
Table 6
Number (%) of Patients with a >/=5% Occurrence Rate By Body System and Treatment Group
Body System and Term |
Cenestin 0.45 mg |
Control |
p-value |
Any Adverse Event %
|
40
|
(75.5%) |
39
|
(76.5%) |
1.0000
|
Body As A Whole |
20
|
(37.7%) |
24
|
(47.1%) |
0.4275
|
Asthenia
|
6
|
(11.3%) |
7
|
(13.7%) |
0.7731
|
Headache
|
6
|
(11.3%) |
8
|
(15.7%) |
0.5748
|
Infection
|
1
|
(1.9%) |
6
|
(11.8%) |
0.0576
|
Pain
|
6
|
(11.3%) |
1
|
(2.0%) |
0.1128
|
Pain abdominal
|
5
|
(9.4%) |
3
|
(5.9%) |
0.7159
|
Cardiovascular |
5
|
(9.4%) |
10
|
(19.6%) |
0.1695
|
Palpitations
|
3
|
(5.7%) |
3
|
(5.9%) |
1.0000
|
Vasodilations
|
2
|
(3.8%) |
4
|
(7.8%) |
0.4324
|
Digestive |
8
|
(15.1%) |
7
|
(13.7%) |
1.0000
|
Nausea
|
5
|
(9.4%) |
2
|
(3.9%) |
0.4374
|
Metabolic and Nutritional |
5
|
(9.4%) |
3
|
(5.9%) |
0.7159
|
Weight increase
|
3
|
(5.7%) |
2
|
(3.9%) |
1.0000
|
Musculoskeletal |
5
|
(9.4%) |
6
|
(11.8%) |
0.7582
|
Arthralgia
|
5
|
(9.4%) |
5
|
(9.8%) |
1.0000
|
Myalgia
|
2
|
(3.8%) |
6
|
(11.8%) |
0.1566
|
Neurological |
15
|
(28.3%) |
19
|
(37.3%) |
0.4044
|
Anxiety
|
3
|
(5.7%) |
1
|
(2.0%) |
0.6179
|
Depression
|
2
|
(3.8%) |
7
|
(13.7%) |
0.0895
|
Insomnia
|
3
|
(5.7%) |
5
|
(9.8%) |
0.4839
|
Nervousness
|
2
|
(3.8%) |
7
|
(13.7%) |
0.0895
|
Paresthesia
|
4
|
(7.5%) |
3
|
(5.9%) |
1.0000
|
Vertigo
|
3
|
(5.7%) |
3
|
(5.9%) |
1.0000
|
Respiratory |
10
|
(18.9%) |
6
|
(11.8%) |
0.4173
|
Upper Respiratory Tract Infection
|
7
|
(13.2%) |
1
|
(2.0%) |
0.0603
|
Rhinitis
|
3
|
(5.7%) |
2
|
(3.9%) |
1.0000
|
Pharyngitis
|
1
|
(1.9%) |
3
|
(5.9%) |
0.3581
|
Urogenital |
19
|
(35.8%) |
7
|
(13.7%) |
0.0124
|
Endometrial thickening
|
10
|
(18.9%) |
4
|
(7.8%) |
0.1503
|
Vaginitis
|
4
|
(7.5%) |
1
|
(2.0%) |
0.3632
|
P-value by Fisher's Exact (2-tail) Test
If a subject experiences the same event more than once, the first occurrence is tabulated. |
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The following additional adverse reactions have been reported with estrogen and/or progestin therapy:
- 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.
- Breasts.
Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.
- Cardiovascular.
Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.
- Gastrointestinal.
Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis, enlargement of hepatic hemangiomas. - Skin.
Chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.
- Eyes.
Retinal vascular thrombosis; intolerance to contact lenses. - Central nervous system.
Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy.
- Miscellaneous.
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; anaphylactoid/anaphylactic reactions including urticaria and angioedema; hypocalcemia; exacerbation of asthma; increased triglycerides.
|