Vivelle-Dot (transdermal estrogen replacement) - 3 Indications

Scroll down for additional information on each indication:

• for the treatment of vasomotor symptoms due to menopause and vulvar and vaginal atrophy due to menopause; approved July of 1996
• for the prevention of postmenopausal osteoporosis; approved August 2000
• for the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure; approval date N/A

General Information

Vivelle-Dot is an estrogen replacement therapy. Vivelle-Dot is designed to deliver estradiol, the primary estrogen produced by the ovaries, via a small patch that is applied twice weekly.

Vivelle-Dot is specifically indicated for the following:

• the treatment of vasomotor symptoms due to menopause and vulvar and vaginal atrophy due to menopause
• for the prevention of postmenopausal osteoporosis
• for the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure

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 post-menopausal women.

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 information)

Side Effects

Adverse reactions associated with Vivelle include (but are not limited to) the following:

• Headache
• Skin irritation at the application site
• Nausea
• Breast tenderness or enlargement
• Back pain
• Vaginal spotting or bleeding

The Vivelle-Dot drug label comes with the following Black Box Warning: Estrogen-Alone Therapy There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older. Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia. Estrogen Plus Progestin Therapy The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI). The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer. The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.

Indication 1 - for the treatment of vasomotor symptoms due to menopause and vulvar and vaginal atrophy due to menopause

approved July of 1996

Dosing/Administration

Start therapy with Vivelle-Dot 0.0375 mg/day applied to the skin twice weekly for the treatment of moderate to severe vasomotor symptoms due to menopause or moderate to severe symptoms of vulvar and vaginal atrophy symptoms due to menopause. Dosage adjustment should be guided by the clinical response.

Indication 2 - for the prevention of postmenopausal osteoporosis

approved August 2000

Dosage/Administration

Start therapy with Vivelle-Dot 0.025 mg per day applied to the skin twice weekly.

Clinical Trial Results

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.

In two controlled clinical trials of 356 subjects, two dose levels of Vivelle were tested. The 0.075 and 0.1 mg doses were superior to a placebo in relieving vasomotor symptoms at week four, and maintained efficacy through weeks eight and 12 of treatment. An additional 12-week placebo-controlled study in 255 patients was performed to test the lowest dose of 0.0375 mg. The 0.0375 mg dose was also superior to a placebo in reducing both the frequency and severity of vasomotor symptoms.

The Vivelle system's possible benefits in the prevention of postmenopausal osteoporosis have also been examined. A 2-year double-blind, randomized, placebo-controlled parallel group study was conducted with a total of 261 individuals. The enrolled group consisted of hysterectomized (161) and non-hysterectomized (100), surgically or naturally menopausal women (within 5 years of menopause), with no evidence of osteoporosis. There was an increase in bone mineral density (BMD) of the AP lumbar spine in all Vivelle groups, compared to a decrease in AP lumbar spine BMD observed in placebo patients. All Vivelle doses were significantly superior to a placebo at all time points with the exception of Vivelle 0.05 mg/day at 6 months. The highest dose of Vivelle was superior to the three lower doses. 

Indication 3 - for the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure

approval date N/A

Dosage/Administration

Start therapy with Vivelle-Dot 0.025 mg per day applied to the skin twice weekly.

Clinical Trial Results

N/A