Activella® ([estradiol/norethindrone acetate] tablets) Indications
and Usage
Activella® 0.5 mg/0.1 mg is indicated in women who have a uterus
for the treatment of moderate to severe vasomotor symptoms associated with menopause
and the prevention of postmenopausal osteoporosis. When prescribing solely for the
prevention of postmenopausal osteoporosis, therapy should only be considered for
women at significant risk of osteoporosis and non-estrogen medications should be
carefully considered.
Activella® 1.0 mg/0.5 mg is also indicated in women who have a uterus
for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated
with menopause. When used solely for the treatment of symptoms of vulvar and vaginal
atrophy, topical vaginal products should be considered.
For additional information about Activella® please refer to Prescribing Information, including boxed
warning.
Activella® Important Safety Information
Estrogens with or without progestins should not be used for the prevention of cardiovascular
disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders
and Dementia in prescribing information.)
The estrogen plus progestin substudy of the Women’s Health Initiative (WHI) reported
increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary
emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age)
during 5.6 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined
with medroxyprogesterone acetate (MPA 2.5 mg) per day, relative to placebo. (See
CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Malignant neoplasms,
Breast cancer in prescribing information.)
The estrogen-alone substudy of the WHI reported increased risks of stroke and deep
vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8
years and 7.1 years, respectively, of treatment with oral conjugated estrogens (CE
0.625 mg) per day, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular
disorders in prescribing information.)
The Women’s Health Initiative Memory Study (WHIMS), a substudy of the WHI study,
reported increased risk of developing probable dementia in postmenopausal women
65 years of age or older during 4 years of treatment with CE 0.625 mg combined with
MPA 2.5 mg and during 5.2 years of treatment with CE 0.625 mg alone, relative to
placebo. It is unknown whether this finding applies to younger postmenopausal women.
(See CLINICAL STUDIES, WARNINGS, Dementia and PRECAUTIONS, Geriatric Use in prescribing
information.)
Other doses of oral conjugated estrogens with medroxyprogesterone acetate and other
combinations and dosage forms of estrogens and progestins were not studied in the
WHI clinical trials and, in the absence of comparable data, these risks should be
assumed to be similar. Because of these trials, estrogens with or without progestins
should be prescribed at the lowest effective doses and for the shortest duration
consistent with treatment goals and risks for the individual woman.
Other warnings include: gallbladder disease, hypercalcemia, and visual abnormalities.
Activella® should not be used in women with any of the following
conditions: undiagnosed abnormal genital bleeding; known, suspected, or history
of cancer of the breast; known or suspected estrogen-dependent neoplasia; active
deep vein thrombosis, pulmonary embolism, or history of these conditions; active
or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke,
myocardial infarction); liver dysfunction or disease; known hypersensitivity to
the ingredients of Activella® 0.5 mg/0.1 mg or Activella®
1.0 mg/0.5 mg; known or suspected pregnancy.
In a clinical trial, the most commonly reported adverse events (reported at a frequency
of ≥5%) were back pain, headache, pain in extremity, nausea, diarrhea, nasopharyngitis,
endometrial thickening, and vaginal hemorrhage.
