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.
In the two pivotal controlled studies, discontinuation of treatment due to an adverse event was required by
5.4 percent of patients receiving ESTRING and 3.9 percent of patients receiving conjugated estrogens vaginal cream.
The most common reasons for withdrawal from ESTRING treatment due to an adverse event were vaginal discomfort and gastrointestinal symptoms.
The adverse events reported with a frequency of 3 percent or greater in the two pivotal controlled studies by
patients receiving ESTRING or conjugated estrogens vaginal cream are listed in Table 4.
Table 4: Adverse Events Reported by 3 Percent or More of Patients Receiving Either ESTRING or Conjugated Estrogens Vaginal Cream in Two Pivotal Controlled Studies
Other adverse events (listed alphabetically) occurring at a frequency of 1 to 3 percent in the two pivotal controlled studies by patients receiving ESTRING include: anxiety, bronchitis, chest pain, cystitis, dermatitis, diarrhea, dyspepsia, dysuria, flatulence, gastritis, genital eruption, urogenital pruritus, hemorrhoids, leg edema, migraine, otitis media, skin hypertrophy, syncope, toothache, tooth disorder, urinary incontinence.
Post-Marketing Experience
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A few cases of toxic shock syndrome (TSS) have been reported in women using vaginal rings.
TSS is a rare, but serious disease that may cause death. Warning signs of TSS include fever, nausea, vomiting, diarrhea, muscle pain,
dizziness, faintness, or a sunburn-rash on face and body.
- A few cases of ring adherence to the vaginal wall, making ring removal difficult, have been reported.
Vaginal wall ulceration or erosion should be carefully evaluated. If an ulceration or erosion has occurred,
consideration should be given to leaving the ring out and not replacing it until healing is complete in
order to prevent the ring from adhering to the healing tissue.
- A few cases of bowel obstruction and vaginal ring use have been reported. Persistent abdominal complaints consistent with obstruction should be carefully evaluated.
The following additional adverse events were reported at least once by patients
receiving ESTRING in the worldwide clinical program, which includes controlled
and uncontrolled studies. A causal relationship with ESTRING 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
Musculoskeletal: arthropathy (including arthrosis)
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
The following additional adverse reactions have been reported with estrogens:
Genitourinary system: abnormal uterine bleeding/spotting; dysmenorrheal/pelvic pain;
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 that may persist when drug is discontinued; erythema multiforme;
erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism, rash
Eyes: retinal vascular thrombosis; intolerance to contact lenses
Central Nervous System: headache; migraine; dizziness; mental depression; exacerbation of chorea; nervousness; mood disturbances;
irritability; exacerbation of epilepsy, dementia
Miscellaneous: increase or decrease in weight; glucose intolerance; aggravation of porphyria;
edema; arthralgias; leg cramps; changes in libido; angioedema; anaphylactoid/anaphylactic reactions;
hypocalcemia (preexisting condition); exacerbation of asthma; increased triglycerides
