Activella (Estradiol/Norethindrone Acetate) Tablets
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Combination hormone replacement therapy for the prevention of osteoporosis and other symptoms associated with Menopause.
Activella has been approved for the treatment of postmenopausal
women with an intact uterus for prevention of osteoporosis. It is
also indicated for several other symptoms associated with
menopause, such as severe vasomotor symptoms and vulvar and vaginal
atrophy. Activella is a combination hormone replacement therapy
(HRT) tablet containing both estrogen and progestin. The tablet is
administered once daily with a dosage of 1 mg of the estrogen
(17beta-estradiol) and 0.5 mg of the progestin (norethindrone
Activella has already been approved in Europe for the prevention
of postmenopausal osteoporosis and has been marketed there under
the name Activelle or Kliovance. Pharmacia & Upjohn, under
terms of an agreement with Novo Nordisk, will be marketing the new
HRT in the U.S.
The effects of Activella on Bone Mineral Density (BMD) was
investigated in the U.S. and in Europe in two multi-center,
placebo-controlled studies. Participants were all postmenopausal
women with intact uteri and baseline BMD values for lumbar spine
within two standard deviations of the mean in healthy young women.
Patients were randomized to groups given different dosages of
either estradiol alone, norethindrone alone, a combination of the
two (Activella), or placebo. Treatment was supplemented with
calcium (500-1000 mg/day). In the United States and European
studies, the mean percentage change in BMD between Activella and
placebo was 5.9% and 6.3%, respectively.
Also, Activella yielded a statistically significant reduction in
serum and urine markers of bone turnover. This effect was apparent
after three months of treatment and was retained for the entire
two-year treatment period.
Common side effects include:
- Breast tenderness/pain
- Upper respiratory tract infections
- Postmenopausal bleeding
Women who have been diagnosed with the following, should
NOT take Activella:
- Known or suspected pregnancy
- Breast cancer
- Estrogen- dependent neoplasia
- Active deep vein thrombosis
- Thromboembolic disorders or stroke
- Undiagnosed genital bleeding
- Liver dysfunction or disease
- Hypersensitivity to any of the active ingredients in the
Women who have had hysterectomies should NOT
take Activella, as the existing data suggests that the combination
therapy of estrogen and progestin may increase risk of glucose
intolerance and less favorable effects on lipid metabolism in women
without a uterus.
Mechanism of Action
Circulating estrogens modulate the pituitary secretion of the
gonadotropins, luteinizing hormone (LH), and follicle-stimulating
hormone (FSH) through a negative feedback mechanism, and estrogen
replacement therapy acts to reduce the elevated levels of these
hormones seen in postmenopausal women.
Progestin compounds enhance cellular differentiation and
generally oppose the actions of estrogens by decreasing estrogen
receptor levels, increasing local metabolism of estrogens to less
active metabolites, or inducing gene products that blunt cellular
responses to estrogen. Progestins exert their effects in target
cells by binding to specific progesterone receptors that interact
with progesterone response elements in target genes. Progesterone
receptors have been identified in the female reproductive tract,
breast, pituitary, hypothalamus, and central nervous system.
Progestins produce similar endometrial changes to those of the
naturally occurring hormone progesterone.
(From FDA Label)
Visit the Novo Nordisk
Pharmaceuticals web site to learn more about Activella and
about other products, research, and services provided by the
company that developed this drug.
Visit the Pharmacia &
Upjohn web site to learn more about the company that acquired
the U.S. rights to Activella.
For more information about osteoporosis, visit the official web