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.
Adverse events reported with Activella 1.0 mg/0.5 mg by investigators in the Phase 3 studies regardless of causality assessment are shown in Table 6.
TABLE 6: ALL TREATMENT-EMERGENT ADVERSE EVENTS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥5% WITH ACTIVELLA 1.0 MG/0.5 MG |
Endometrial Hyperplasia Study
(12-Months) |
Vasomotor Symptoms Study
(3-Months) |
Osteoporosis Study
(2 years) |
| Activella 1.0 mg/0.5 mg | 1 mg E2 | Activella 1.0 mg/0.5 mg | Placebo | Activella 1.0 mg/0.5 mg | Placebo |
| (n=295) | (n=296) | (n=29) | (n=34) | (n=47) | (n=48) |
| | | | | | |
Body as a Whole | | | | | | |
Back Pain | 6% | 5% | 3% | 3% | 6% | 4% |
Headache | 16% | 16% | 17% | 18% | 11% | 6% |
| | | | | | |
Digestive System | | | | | | |
Nausea | 3% | 5% | 10% | 0% | 11% | 0% |
Gastroenteritis | 2% | 2% | 0% | 0% | 6% | 4% |
| | | | | | |
Nervous System | | | | | | |
Insomnia | 6% | 4% | 3% | 3% | 0% | 8% |
Emotional Lability | 1% | 1% | 0% | 0% | 6% | 0% |
| | | | | | |
Respiratory System | | | | | | |
Upper Respiratory Tract Infection | 18% | 15% | 10% | 6% | 15% | 19% |
Sinusitis | 7% | 11% | 7% | 0% | 15% | 10% |
| | | | | | |
Metabolic and Nutritional | | | | | | |
Weight Increase | 0% | 0% | 0% | 0% | 9% | 6% |
| | | | | | |
Urogenital System | | | | | | |
Breast Pain | 24% | 10% | 21% | 0% | 17% | 8% |
Post-Menopausal Bleeding | 5% | 15% | 10% | 3% | 11% | 0% |
Uterine Fibroid | 5% | 4% | 0% | 0% | 4% | 8% |
Ovarian Cyst | 3% | 2% | 7% | 0% | 0% | 8% |
| | | | | | |
Resistance mechanism | | | | | | |
Infection Viral | 4% | 6% | 0% | 3% | 6% | 6% |
Moniliasis Genital | 4% | 7% | 0% | 0% | 6% | 0% |
| | | | | | |
Secondary Terms | | | | | | |
Injury Accidental | 4% | 3% | 3% | 0% | 17%
| 4% |
Other Events | 2% | 3% | 3% | 0% | 6% | 4% |
Adverse events reported with Activella 0.5 mg/0.1 mg by investigators during the Phase 3 study regardless of causality assessment are shown in Table 7.
TABLE 7: ALL TREATMENT-EMERGENT ADVERSE EVENTS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥5% WITH ACTIVELLA 0.5 MG/0.1 MG |
Activella 0.5 mg/0.1 mg
|
Placebo
|
| (n=194) | (n=200) |
Body as a Whole | | |
Back Pain | 10% | 4% |
Headache | 22% | 19% |
Pain in extremity | 5% | 4% |
| | |
Digestive System | | |
Nausea | 5% | 4% |
Diarrhea | 6% | 6% |
| | |
Respiratory System | | |
Nasopharyngitis | 21% | 18% |
| | |
Urogenital System | | |
Endometrial thickening | 10% | 4% |
Vaginal hemorrhage | 26% | 12% |
The following adverse reactions have been reported with estrogen 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; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.
2. Breasts
Tenderness, 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; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas.
5. Skin
Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.
6. Eyes
Retinal vascular thrombosis, intolerance to contact lenses.
7. Central nervous system
Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; probable dementia.
8. Miscellaneous
Increase or decrease in weight; aggravation of porphyria; edema; leg cramps; changes in libido; fatigue; reduced carbohydrate tolerance; anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides; back pain; arthralgia; myalgia.
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