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.
Activella® Important Safety Information
For additional information about Activella® please refer to Prescribing Information, including boxed warning.
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 the 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 the 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 the 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 the 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; 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.
Vagifem® (estradiol vaginal tablets) Indications and Usage
Vagifem® is indicated for the treatment of atrophic vaginitis.
Vagifem® Important Safety Information
For additional information about Vagifem® please refer to Prescribing Information, including boxed warning.
ESTROGENS HAVE BEEN REPORTED TO INCREASE THE RISK OF ENDOMETRIAL CARCINOMA.
Three independent, case-controlled studies have reported an increased risk of endometrial cancer in postmenopausal women exposed to exogenous estrogens for more than one year. This risk was independent of the other known risk factors for endometrial cancer. These studies are further supported by the finding that incident rates of endometrial cancer have increased sharply since 1969 in eight different areas of the United States with population-based cancer-reporting systems, an increase of which may be related to the rapidly expanding use of estrogens during the last decade.
The three case-controlled studies reported that the risk of endometrial cancer in estrogen users was about 4.5 to 13.9 times greater than in nonusers. The risk appears to depend on both duration and treatment and on estrogen dose. In view of these findings, when estrogens are used for the treatment of menopausal symptoms, the lowest dose that will control symptoms should be utilized and medication should be discontinued as soon as possible. When prolonged treatment is medically indicated, the patient should be reassessed, on at least a semiannual basis, to determine the need for continued therapy.
Close clinical surveillance of all women taking estrogens is important. In all cases of undiagnosed persistent or reoccurring abnormal vaginal bleeding, adequate diagnostic measures should be undertaken to rule out malignancy. There is no evidence at present that "natural" estrogens are more or less hazardous than "synthetic" estrogens at equi-estrogenic doses.
Other warnings include: induction of malignant neoplasms, gallbladder disease, effects similar to those caused by estrogen-progestogen oral contraceptives (such as thromoboembolic disease, hepatic adenoma, elevated blood pressure, worsening of glucose tolerance), hypercalcemia, and rarely, trauma induced by the Vagifem® applicator.
In a placebo-controlled clinical trial, the most commonly reported adverse events included: headache (9%), abdominal pain (7%), upper respiratory tract infection (5%), genital moniliasis (5%), and back pain (7%).
The use of Vagifem® is contraindicated in women who exhibit one or more of the following: known or suspected breast carcinoma, known or suspected estrogen-dependent neoplasia, e.g., endometrial carcinoma, abnormal genital bleeding of unknown etiology, known or suspected pregnancy, porphyria, hypersensitivity to any Vagifem® constituents, active thrombophlebitis or thromboembolic disorders, or a past history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast malignancy).
