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
Estrogel Side Effects, and Drug Interactions - Estradiol Gel
Estrogel Side Effects, and Drug Interactions - Estradiol Gel
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.
EstroGel 1.25 g was studied in two well-controlled 12-week
clinical trials. Incidence of adverse experiences • 5% for 1.25 g EstroGel and
placebo is given below in Table 3.
|
TABLE 3 Incidence of Treatment-Emergent Signs and Symptoms
• 5% By COSTART Body System and by Descending Frequency of Occurrence
in the EstroGel Treatment Group for the Intent-to-Treat Safety Population
in Two Well-Controlled Clinical Studies (Expressed as % of Treatment Group)
|
|
BODY SYSTEM/Treatment-Emergent Signs and Symptoms
|
EstroGel 1.25 g day (n=168)
|
Placebo (n=73)
|
|
BODY AS A WHOLE
|
|
Headache
|
20.2
|
17.8
|
|
Infectiona
|
17.3
|
6.8
|
|
Painb
|
7.1
|
11.0
|
|
Abdominal Pain
|
7.7
|
1.4
|
|
Back Pain
|
4.8
|
4.1
|
|
Flu Syndrome
|
5.4
|
1.4
|
|
Asthenia
|
4.8
|
4.1
|
|
CARDIOVASCULAR SYSTEM
|
|
Palpitations
|
0.6
|
1.4
|
|
DIGESTIVE SYSTEM
|
|
Nausea
|
6.0
|
4.1
|
|
Flatulence
|
6.5
|
5.5
|
|
Diarrhea
|
4.2
|
0.0
|
|
METABOLIC and NUTRITIONAL SYSTEMS
|
|
Weight Gain
|
2.4
|
0.0
|
|
NERVOUS SYSTEM
|
|
Nervousness
|
2.4
|
1.4
|
|
Depression
|
3.0
|
2.7
|
|
Anxiety
|
1.8
|
0.0
|
|
RESPIRATORY SYSTEM
|
|
Sinusitis
|
3.6
|
1.4
|
|
Rhinitis
|
2.4
|
6.8
|
|
SKIN AND APPENDAGES
|
|
Rashc
|
7.1
|
5.5
|
|
Pruritusc
|
4.8
|
2.7
|
|
Application Site Reaction
|
0.6
|
0.0
|
|
UROGENITAL
|
|
Breast Pain
|
12.5
|
9.6
|
|
Metrorrhagia
|
3.0
|
0.0
|
|
Endometrial Disorderd
|
1.8
|
1.4
|
|
Vaginitis
|
8.9
|
4.1
|
|
Pap Smear Suspiciouse
|
5.4
|
2.7
|
|
Vaginal Hemorrhage
|
1.2
|
0.0
|
|
a Infection: upper respiratory infection, common cold,
eye infection.
|
|
b Pain: generalized and extremity aches/pains, cramps.
|
|
c Rash and Pruritus: More than half of the EstroGel treated
patients who had pruritus reported itching At a body site other than the
arms or reported generalized itching or itching skin. Similarly, most
of The EstroGel treated patients with rash had rash on one or more areas
of the body in addition to the Arms.
|
|
d Endometrial Disorder: proliferative endometrium, benign
endometrial disorders.
|
|
e Pap Smear Suspicious: atypical squamous cells of undetermined
significance, inflammatory changes, Epithelial cell abnormality.
|
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; bloating; diarrhea; dyspepsia;
constipation; vomiting; abdominal cramps; 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.
8. Miscellaneous: Increase or decrease in weight; reduced
carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps;
changes in libido; anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation
of asthma; increased triglycerides.
DRUG INTERACTIONS
D. Drug and 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 levels, 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 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
total circulating corticosteroids and sex steroids, respectively. Free hormone
concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin
substrate, alpha-1-antitrypsin, ceruloplasmin).
4. Increased plasma HDL and HDL2 cholesterol subfraction
concentrations, reduced LDL cholesterol concentration, increased triglyceride
levels.
5. Impaired glucose tolerance.
6. Reduced response to metyrapone test.
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