Home » Drug Information » FDA Approved Drugs » 2002
Medical Areas: Musculoskeletal | Obstetrics/Gynecology (Women’s Health)
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Vivelle-Dot (estradiol transdermal system)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved May 2002
Treatment Area: Post-menopausal osteoporosis
Vivelle-Dot has been approved by the FDA for the prevention of
post-menopausal osteoporosis. This estrogen replacement therapy is
currently marketed for the treatment of menopausal symptoms.
Vivelle-Dot is a smaller, revised version of the original
Vivelle transdermal product, which was approved in 2000.
Vivelle-Dot is designed to deliver estradiol, the primary estrogen
produced by the ovaries, via a small patch that is applied twice
weekly. The product utilizes Noven's DOT Matrix transdermal
drug delivery technology to effectively deliver the drug through
the small patch surface area. DOT Matrix patches use ratios of
silicone, acrylic and drug to regulate the rate of delivery through
the skin and into the bloodstream.
With the approval for post-menopausal osteoporosis, Vivelle-Dot
is now available in five dosage strengths: 0.0250, 0.0375, 0.0500,
0.0750 and 0.1000 mg/day. The new 0.0250 mg/day strength is only
indicated for the prevention of post-menopausal osteoporosis (and
not for the treatment of menopausal symptoms).
Note: Vivelle-Dot was shown to be bioequivalent to Vivelle, the
The effectiveness of Vivelle for the prevention of
post-menopausal osteoporosis was evaluated in a two-year,
double-blind, randomized, placebo-controlled, parallel-group study.
The trial included a total of 261 hysterectomized (161) and
non-hysterectomized (100), surgically or naturally menopausal women
with no evidence of osteoporosis. One hundred ninety-four of the
subjects were randomized to receive one of four doses of Vivelle
(0.1000, 0.0500, 0.0375 or 0.0250 mg/day), and 67 subjects were
randomized to receive a placebo. Over two years, the study systems
were applied to the buttock or the abdomen twice a week.
Two hundred thirty-two (89%) of the randomized subjects (173
receiving Vivelle, 59 receiving placebo) contributed data to the
primary efficacy measurement: analysis of percent change from
baseline in bone mineral density (BMD) of the AP lumbar spine. An
increase in BMD of the AP lumbar spine was observed in all Vivelle
dose groups; in contrast, a decrease in AP lumbar spine BMD was
observed in subjects receiving placebo. All doses of Vivelle were
significantly superior to placebo at all time points, with the
exception of Vivelle 0.0500 mg/day at six months.
A secondary efficacy measurement in the trial was an analysis of
percent change from baseline in femoral neck BMD. Results showed
that all doses of Vivelle were significantly superior to the
placebo at 24 months. Additionally, the highest dose of Vivelle was
more effective than the placebo at all time points.
Systemic adverse events reported with Vivelle in clinical trials
include (but are not limited to) the following:
- Headache (32.3% for Vivelle, 28% for placebo)
- Breast tenderness (10% for Vivelle, 0% for placebo)
- Fluid retention (2.4% for Vivelle, 1.9% for placebo)
- Back pain (9% for Vivelle, 6.4% for placebo)
Mechanism of Action
Estrogens are largely responsible for the development and
maintenance of the female reproductive system and secondary sexual
characteristics. Although circulating estrogens exist in a dynamic
equilibrium of metabolic interconversions, estradiol is the
principal intracellular human estrogen and is substantially more
potent than its metabolites, estrone and estriol, at the receptor
level. The primary source of estrogen in normally cycling adult
women is the ovarian follicle, which secretes 70 to 500 µg of
estradiol daily, depending on the phase of the menstrual cycle.
After menopause, most endogenous estrogen is produced by conversion
of androstenedione, secreted by the adrenal cortex, to estrone by
peripheral tissues. Thus, estrone and the sulfate conjugated form,
estrone sulfate, are the most abundant circulating estrogens in
Estrogens act through binding to nuclear receptors in
estrogen-responsive tissues. To date, two estrogen receptors have
been identified. They vary in proportion from tissue to tissue.
Circulating estrogens modulate the pituitary secretion of the
gonadotropins, luteinizing hormone (LH) and follicle stimulating
hormone (FSH), through a negative feedback mechanism. Estrogen
replacement therapy acts to reduce the elevated levels of these
hormones seen in post-menopausal women. (from FDA label