Activella (Estradiol/Norethindrone Acetate) Tablets

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 acetate).

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
• Headache
• 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 drug

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.

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 sites of

• the National Osteoporosis Foundation
  and
  
• the International Osteoporosis Foundation.