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
Estring Side Effects, and Drug Interactions - Estradiol (vaginal)
Estring Side Effects, and Drug Interactions - Estradiol (vaginal)
SIDE EFFECTS
Vaginal Cream
The following additional adverse reactions have been reported with
estrogen therapy (see WARNINGS
regarding induction of neoplasia, adverse effects on the fetus,
increased incidence of gallbladder
disease, cardiovascular
disease, elevated blood
pressure, and hypercalcemia).
Genitourinary System: Changes in vaginal
bleeding pattern and
abnormal withdrawal
bleeding or flow; breakthrough
bleeding, spotting; increase in size of uterine
leiomyomata; vaginal
candidiasis; change in amount of cervical
secretion.
Breasts: Tenderness, enlargement.
Gastrointestinal: Nausea, vomiting; abdominal
cramps, bloating; cholestatic jaundice; increased incidence
of gallbladder disease.
Skin: Chloasma or melasma
which may persist when drug is discontinued; erythema
multiforme; erythema
nodosum; hemorrhagic
eruption; loss of scalp
hair; hirsutism.
Eyes: Steepening of corneal curvature; , intolerance
to contact lenses.
Central Nervous System: Headache, migraine, dizziness;
mental depression; chorea.
Miscellaneous: Increase or decrease in weight; reduced
carbohydrate tolerance; aggravation of porphyria; edema; changes
in libido.
Vaginal Ring
The biological safety
of the silicone elastomer
has been studied in various in vitro and in vivo test
models. The results show that the silicone
elastomer is non-toxic, non-pyrogenic, non-irritating, and non-sensitizing.
Long-term implantation
induced encapsulation
equal to or less than the negative
control (polyethylene)
used in the USP test. No toxic
reaction or tumor
formation was observed
with the silicone elastomer.
In general, estradiol
vaginal ring
was well tolerated. In the
two pivotal controlled studies, discontinuation of treatment
due to an adverse event was required by 5.4% of patients receiving
the estradiol vaginal
ring and 3.9% of patients
receiving conjugated estrogens vaginal
cream. The most common reasons for withdrawal
from estradiol vaginal
ring treatment
due to an adverse event were vaginal
discomfort and gastrointestinal
symptoms.
The adverse events reported with a frequency of 3% or greater in
the two pivotal controlled studies by patients receiving the estradiol
vaginal ring or conjugated estrogens vaginal
cream are listed in TABLE
6.
| TABLE 6 Adverse Events Reported
by 3% or More of Patients Receiving Either the Estradiol Vaginal
Ring or Conjugated Estrogens Vaginal Cream in Two Pivotal
Controlled Studies |
|
Adverse Event
|
Estradiol Vaginal Ring (n=257) % |
Conjugated Estrogens Vaginal Cream (n=129)
% |
| Musculoskeletal |
|
|
6 |
8 |
|
|
4 |
2 |
|
|
3 |
5 |
|
|
2 |
4 |
| CNS/Peripheral Nervous System |
|
|
13 |
16 |
| Psychiatric |
|
|
4 |
|
| Gastrointestinal |
|
|
4 |
2 |
|
|
3 |
2 |
| Respiratory |
|
|
5 |
6 |
|
|
4 |
3 |
|
|
1 |
3 |
| Urinary |
|
|
2 |
7 |
| Female Reproductive |
|
|
7 |
3 |
|
|
5 |
2 |
|
|
5 |
5 |
|
|
4 |
5 |
|
|
4 |
6 |
|
|
1 |
7 |
| Resistance Mechanisms |
|
|
6 |
7 |
| Body as a Whole |
|
|
3 |
2 |
|
|
2 |
3 |
|
|
1 |
4 |
| Miscellaneous |
|
|
2 |
3 |
Other adverse events (listed alphabetically) occurring at a frequency
of 1 to 3% in the two pivotal controlled studies by patients receiving
the estradiol vaginal
ring include: anxiety,
bronchitis, chest pain,
cystitis, dermatitis, diarrhea, dyspepsia, dysuria, flatulence,
gastritis, genital eruption, genital
pruritus, hemorrhoids, leg
edema, migraine, otitis
media, skin hypertrophy, syncope, toothache, tooth
disorder, urinary incontinence.
The following additional adverse events were reported at least
once by patients receiving the estradiol
vaginal ring
in the worldwide clinical program, which includes controlled and
uncontrolled studies. A causal relationship with the estradiol
vaginal ring
has not been established.
Body as a Whole: Allergic reaction.
CNS/Peripheral Nervous System: Dizziness.
Gastrointestinal: Enlarged abdomen, vomiting.
Metabolic/Nutritional Disorders: Weight decrease
or increase.
Psychiatric: Depression, decreased libido, nervousness.
Reproductive: Breast engorgement, breast
enlargement, intermenstrual bleeding, genital
edema, vulval disorder.
Skin/Appendages: Pruritus, pruritus
ani.
Urinary: Micturition frequency, urethral
disorder.
Vascular: Thrombophlebitis.
Vision: Abnormal vision.
Vaginal Tablets
Adverse Events Generally Have Been Mild: Vaginal
spotting, vaginal discharge, allergic
reaction, and skin rash.
Adverse events with an incidence
of 5% or greater are reported for two comparative trials. Data for
patients receiving either estradiol
vaginal tablets or placebo
in the double blind
study are listed in TABLE 7, and data for patients receiving estradiol
vaginal tablets in the
open label
comparator study are listed in TABLE 8.
| TABLE 7 Adverse Events Reported
in 5% or Greater Number of Patients Receiving Estradiol Vaginal
Tablets in the Placebo Controlled Trial. |
| |
Estradiol Vaginal Tablets |
Placebo |
| |
(n=91) |
(n=47) |
|
Adverse Event
|
% |
% |
| Headache |
9 |
6 |
| Abdominal Pain |
7 |
4 |
| Upper Respiratory Tract Infection |
5 |
4 |
| Moniliasis Genital |
5 |
2 |
| Back Pain |
7 |
6 |
| TABLE 8 Adverse Events Reported
in 5% or Greater Number of Patients Receiving Estradiol Vaginal
Tablets in the Open Label Study. |
| Adverse Event |
Estradiol (n=80) % |
| Pruritus Genital |
6 |
| Headache |
10 |
| Upper Respiratory Tract Infection |
11 |
Other Adverse Events That Occurred in 3-5% of Estradiol Vaginal
Tablet Subjects Included: Allergy, bronchitis, dyspepsia,
haematuria, hot flashes, insomnia, pain, sinusitis, vaginal
discomfort, vaginitis. A causal relationship to estradiol
vaginal tablets has
not been established.
DRUG INTERACTIONS
See PRECAUTIONS.
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