ADVERSE REACTIONS
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 ESTRING 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.
| ADVERSE EVENT | ESTRING (n = 257) % | Conjugated Estrogens Vaginal Cream (n = 129) % |
|---|---|---|
Musculoskeletal | ||
Back Pain | 6 | 8 |
Arthritis | 4 | 2 |
Arthralgia | 3 | 5 |
Skeletal Pain | 2 | 4 |
CNS/Peripheral Nervous System | ||
Headache | 13 | 16 |
Psychiatric | ||
Insomnia | 4 | 0 |
Gastrointestinal | ||
Abdominal Pain | 4 | 2 |
Nausea | 3 | 2 |
Respiratory | ||
Upper Respiratory Tract Infection | 5 | 6 |
Sinusitis | 4 | 3 |
Pharyngitis | 1 | 3 |
Urinary | ||
Urinary Tract Infection | 2 | 7 |
Female Reproductive | ||
Leukorrhea | 7 | 3 |
Vaginitis | 5 | 2 |
Vaginal Discomfort/Pain | 5 | 5 |
Vaginal Hemorrhage | 4 | 5 |
Asymptomatic Genital Bacterial Growth | 4 | 6 |
Breast Pain | 1 | 7 |
Resistance Mechanisms | ||
Genital Moniliasis | 6 | 7 |
Body as a Whole | ||
Flu-Like Symptoms | 3 | 2 |
Hot Flushes | 2 | 3 |
Allergy | 1 | 4 |
Miscellaneous | ||
Family Stress | 2 | 3 |
Postmarketing Experience
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.
Vaginal erosion, vaginal ulceration, adherence of the vaginal ring to the vaginal wall:
- •
- Cases of ring adherence to the vaginal wall, making ring removal difficult, have occurred. Some cases have required surgical removal of vaginal rings.
- •
- Cases of vaginal erosion and vaginal ulceration that may manifest as vaginal irritation, erythema. abrasion or spotting have occurred.
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.
Cases of bowel obstruction and vaginal ring use have been reported. Persistent abdominal complaints consistent with obstruction should be carefully evaluated.
Cases of hypersensitivity have been reported.
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