BOX WARNING CARDIOVASCULAR AND OTHER RISKS
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.)
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.)
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.)
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.)
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.
|
| |
ACTIVELLA SUMMARY
CARDIOVASCULAR AND OTHER RISKS
Activella® is a single tablet containing an estrogen, estradiol (E2), and a progestin, norethindrone acetate (NETA), for oral administration. Each tablet contains 1 mg estradiol and 0.5 mg norethindrone acetate and the following excipients: lactose monohydrate, starch (corn), copovidone, talc, magnesium stearate, hypromellose and triacetin.
Activella® therapy is indicated in women with an intact uterus for the:
-
Treatment of moderate to severe vasomotor symptoms associated with the menopause. There is no adequate evidence that estrogens are effective for nervous symptoms or depression that might occur during menopause and they should not be used to treat these conditions.
-
Treatment of vulvar and vaginal atrophy.
-
Prevention of postmenopausal osteoporosis.
Most prospective studies of efficacy for the osteoporosis prevention indication have been carried out in white postmenopausal women, without stratification by other risk factors, and tend to show a universally beneficial effect on bone. Since estrogen administration is associated with risk, patient selection must be individualized based on the balance of risks and benefits.
Case-control studies have shown an approximately 60-percent reduction in hip and wrist fractures in women whose estrogen replacement was begun within a few years after menopause. Studies also suggest that estrogen reduces the rate of vertebral fractures. When estrogen therapy is discontinued, bone mass declines at a rate comparable to the immediate postmenopausal period. White and Asian women are at higher risk for osteoporosis than black women, and thin women are at a higher risk than heavier women, who generally have higher endogenous estrogen levels. Early menopause is one of the strongest predictors for the development of osteoporosis. Other factors associated with osteoporosis include genetic factors (small build, family history), lifestyle (cigarette smoking, alcohol abuse, sedentary exercise habits) and nutrition (below average body weight and dietary calcium intake).
The mainstays of prevention and management of osteoporosis are weight-bearing exercise, adequate calcium intake, and, when indicated, estrogen. Postmenopausal women absorb dietary calcium less efficiently than premenopausal women and require an average of 1500 mg/day of elemental calcium to remain in neutral calcium balance. The average calcium intake in the USA is 400-600 mg/day. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake.
|
|
NEWS HIGHLIGHTS
Published Studies Related to Activella (Estradiol)
Sexual function in women on estradiol or venlafaxine for hot flushes: a
randomized controlled trial. [2014]
estradiol or venlafaxine for hot flushes... CONCLUSION: Overall sexual function among nondepressed midlife women experiencing
Effect of estradiol valerate on endometrium thickness during clomiphene
citrate-stimulated ovulation. [2014]
CONCLUSIONS: We concluded that the addition of 6 mg/day EV following the CC
[Efficacy and safety of a combined oral contraceptive containing drospirenone 3
mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric
disorder: a randomized, double blind placebo-controlled study]. [Article in Chinese] [2014]
with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD)... CONCLUSIONS: YAZ could improve symptoms of PMDD better than placebo, while
Effects of tibolone or continuous combined oestradiol/norethisterone acetate on
glucose and insulin metabolism. [2013]
insulin metabolism in postmenopausal women... CONCLUSIONS: Tibolone reduces insulin sensitivity. Healthy postmenopausal women
Impact of estradiol valerate/dienogest on work productivity and activities of
daily living in women with heavy menstrual bleeding. [2013]
estradiol valerate/dienogest (E2V/DNG; Qlaira(®)/Natazia(®)) compared to placebo... CONCLUSIONS: E2V/DNG was shown to have a consistent positive impact on work
Clinical Trials Related to Activella (Estradiol)
Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fasting Conditions [Completed]
The objective of this study was to determine and compare the rate and extent of absorption
of norethindrone and unconjugated estradiol from a test formulation of
Estradiol/Norethindrone Acetate Tablets, 1 mg/0. 5 mg versus the reference Activella® (1 mg
estradiol/0. 5 mg norethindrone acetate) Tablets under fasting conditions.
Estradiol/Norethindrone Acetate Tablets, 1/0.5 mg Under Fed Conditions [Completed]
The objective of this study was to determine and compare the rate and extent of absorption
of norethindrone and unconjugated estradiol from a test formulation of
Estradiol/Norethindrone Acetate Tablets, 1 mg/0. 5 mg versus the reference Activella® (1 mg
estradiol/0. 5 mg norethindrone acetate) Tablets under fed conditions.
Efficacy and Tolerability Study of Progesterone Vaginal Tablets (Endometrin®) in Menopausal Women Treated by Estrogen [Not yet recruiting]
Endometrial Safety Study [Completed]
Efficacy of Tibolone Versus Transdermal E2/NETA on Sexual Function in Naturally Postmenopausal Women (P06089) [Completed]
Tibolone has been registered for treatment of menopausal symptoms. It is, however, not known
what the effects are of tibolone in postmenopausal women diagnosed with sexual dysfunction.
This is important because there is currently no approved treatment of libido problems in
postmenopausal women. Therefore, the primary aim of this study was to compare the effects of
tibolone with an estrogen/progestogen skin patch in postmenopausal women diagnosed sexual
dysfunction.
Reports of Suspected Activella (Estradiol) Side Effects
Breast Cancer Female (4),
Product Substitution Issue (2),
Night Sweats (1),
Drug Ineffective (1),
Haemorrhage (1),
Wrong Drug Administered (1),
Vaginal Haemorrhage (1),
Hot Flush (1),
Hypertrichosis (1),
Depression (1), more >>
|
|
|
|
Page last updated: 2015-08-10
|
