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. 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 13-week clinical trial that included 225 postmenopausal women treated with Femring and 108 women treated with placebo vaginal rings, adverse events that occurred at a rate of ≥ 2% are summarized in Table 6. Incidence of AEs Occurring in ≥2% of Subjects Presented in Descending Frequency of Preferred Term.
Table 6. Incidence of AEs Occurring in ≥2% of Subjects Presented in Descending Frequency of Preferred Term | Adverse Event |
Placebo
(n = 108) |
Estradiol
0.05 mg/day
(n = 113) |
Estradiol
0.10 mg/day
(n = 112) |
| n (%) | n (%) | n (%) |
| Headache (NOS) | 10 (9.3) | 8 (7.1) | 11 (9.8) |
| Intermenstrual Bleeding | 2 (1.9) | 9 (8.0) | 11 (9.8) |
| Vaginal Candidiasis | 3 (2.8) | 7 (6.2) | 12 (10.7) |
| Breast Tenderness | 2 (1.9) | 7 (6.2) | 12 (10.7) |
| Back Pain | 4 (3.7) | 7 (6.2) | 4 (3.6) |
| Genital Disorder Female (NOS) | 9 (8.3) | 3 (2.7) | 3 (2.7) |
| Upper Respiratory Tract Infection (NOS) | 6 (5.6) | 5 (4.4) | 4 (3.6) |
| Abdominal Distension | 3 (2.8) | 8 (7.1) | 3 (2.7) |
| Vaginal discharge | 9 (8.3) | 2 (1.8) | 3 (2.7) |
| Vulvovaginitis (NOS) | 7 (6.5) | 6 (5.3) | 1 (0.9) |
| Nausea | 5 (4.6) | 3 (2.7) | 2 (1.8) |
| Arthralgia | 4 (3.7) | 2 (1.8) | 2 (1.8) |
| Sinusitis (NOS) | 2 (1.9) | 2 (1.8) | 4 (3.6) |
| Uterine Pain | 1 (0.9) | 2 (1.8) | 5 (4.5) |
| Nasopharyngitis | 3 (2.8) | 2 (1.8) | 2 (1.8) |
| Pain in Limb | 3 (2.8) | 1 (0.9) | 3 (2.7) |
| Urinary Tract Infection (NOS) | 2 (1.9) | 1 (0.9) | 4 (3.6) |
| Vaginal Irritation | 4 (3.7) | 1 (0.9) | 2 (1.8) |
AE = adverse event; NOS = not otherwise specified
The following additional adverse reactions have been reported with estrogens 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; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.
2. Breasts
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, vomiting, abdominal cramps, bloating; 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; pruritis, 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; dementia.
8. Miscellaneous
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
Post-Marketing Experience
- 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 or bladder wall, making ring removal difficult, have been reported in women using vaginal rings. Patients should be carefully evaluated for vaginal or bladder wall ulceration or erosion. If an ulceration or erosion has occurred, consideration should be given to leaving the ring out and not replacing it until healing is complete to prevent the ring from adhering to the vaginal tissue.
- A few cases of bowel obstruction associated with vaginal ring use have been reported. Persistent abdominal complaints consistent with obstruction should be carefully evaluated.
- A few cases of inadvertent ring insertion into the urinary bladder, which may require surgical removal, have been reported for women using vaginal rings. Persistent unexplained urinary symptoms should be carefully evaluated.
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