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.
Divigel® was studied at doses of 0.25, 0.5 and 1.0 g/day in a 12-week, double-blind, placebo-controlled study that included a total of 495 postmenopausal women (86.5% Caucasian). The adverse events that occurred at a rate greater than 5% in any of the treatment groups are summarized in Table 5.
Table 5: Number (%) of Subjects with Common Adverse Events* in a 12-Week Placebo- Controlled Study of Divigel® |
* Adverse events reported by ≥5% of patients in any treatment group.
|
| Divigel ® | Placebo |
| 0.25 g/day | 0.5 g/day | 1.0 g/day | |
| SYSTEM ORGAN CLASS | N=122 | N=123 | N=125 | N=125 |
| Preferred Term | n (%) | n (%) | n (%) | n (%) |
| INFECTIONS & INFESTATIONS | | | | |
| Nasopharyngitis | 7 (5.7) | 5 (4.1) | 6 (4.8) | 5 (4.0) |
| Upper Respiratory Tract Infection | 7 (5.7) | 3 (2.4) | 2 (1.6) | 2 (1.6) |
| Vaginal mycosis | 1 (0.8) | 3 (2.4) | 8 (6.4) | 4(3.2) |
| REPRODUCTIVE SYSTEM & BREAST DISORDERS | | | | |
| Breast Tenderness | 3 (2.5) | 7 (5.7) | 11 (8.8) | 2 (1.6) |
| Metrorrhagia | 5 (4.1) | 7 (5.7) | 12 (9.6) | 2 (1.6) |
In a 12-week placebo-controlled study of Divigel®, application site reactions were seen in <1% of subjects.
The following additional adverse reactions have been reported with estrogen and/or progestin therapy.
- 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; vaginal discharge.
- Breasts: Tenderness; enlargement, pain, nipple discharge, galactorrhea, fibrocystic breast changes; breast cancer; nipple pain.
- 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; abdominal pain.
- Skin: Chloasma or melasma, which may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus; rash.
- Eyes: Retinal vascular thrombosis, intolerance to contact lenses.
- Central Nervous System: Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.
- Miscellaneous: Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgias; leg cramps; changes in libido; urticaria; angioedema; anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides; muscle cramps.
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