ACTIVELLA SIDE EFFECTS
- Generic Name: estradiol, norethindrone acetate
- Brand Name: Activella
- Drug Class: Estrogens/Progestins-HRT
SIDE EFFECTS
The following serious adverse reactions are discussed elsewhere in the labeling:
- Cardiovascular Disorders.
- Malignant Neoplasms.
Clinical Trials Experience
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.
Adverse reactions reported with Activella 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1.
TABLE 1: ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 1 MG/0.5 MG
| Endometrial Hyperplasia Study (12-Months) | Vasomotor Symptoms Study (3-Months) | Osteoporosis Study (2-Years) | ||||
| Activella 1 mg/0.5 mg (n=295) |
1 mg E2 (n=296) |
Activella1 mg/0.5 mg (n=29) |
Placebo (n=34) |
Activella1 mg/0.5 mg (n=47) |
Placebo (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 | 18% | 15% | 10% | 6% | 15% | 19% |
| Tract Infection | ||||||
| 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% |
| * including one upper extremity fracture in each group | ||||||
Adverse reactions reported with Activella 0.5 mg/0.1 mg by investigators during clinical trials regardless of causality assessment are shown in Table 2.
TABLE 2: ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 0.5 MG/0.1 MG<
| Activella 0.5 mg/0.1 mg (n=194) |
Placebo (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% |
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Activella. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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.
Breast
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; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis.
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.
Eyes
Retinal vascular thrombosis, intolerance to contact lenses.
Central Nervous System
Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.
Miscellaneous
Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.
SRC: NLM .