Imvexxy (estradiol vaginal inserts)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved May 2018

Specific Treatments:

moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause

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General Information

Imvexxy is a bio-identical vaginal estrogen. It is an estrogen replacement therapy. 

Imvexxy is specifically indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

Imvexxy is supplied as a vaginal insert containing 4 mcg or 10 mcg estradiol. The recommended dose is 1 vaginal insert daily for 2 weeks, followed by 1 insert twice weekly. 

Clinical Results

FDA Approval

The FDA approval of Imvexxy was based on a 12-week, randomized, double-blind, placebo-controlled, parallel-group trial which enrolled 574 generally healthy postmenopausal women between 40 to 75 years of age who at baseline assessment had ≤5 percent superficial cells on a vaginal smear, a vaginal pH >5.0, and also identified, at baseline, moderate to severe dyspareunia as the most bothersome symptom to her. Greater than 90% of women also reported moderate to severe vaginal dryness at baseline. Treatment groups included 4 mcg Imvexxy (n=191), 10 mcg Imvexxy (n=191), and placebo (n=192). All women were assessed for improvement in the mean change from Baseline to Week 12 for the co-primary efficacy variables of: most bothersome moderate to severe symptom of dyspareunia, percentage of vaginal superficial and percentage of vaginal parabasal cells on a vaginal smear, and vaginal pH. Imvexxy 4 mcg and 10 mcg inserts were statistically superior to placebo in reducing the severity of moderate to severe dyspareunia at Week 12. A statistically significant increase in the percentage of superficial cells and a corresponding statistically significant decrease in the percentage of parabasal cells on a vaginal smear was also demonstrated for Imvexxy 4 and 10 mcg inserts. The mean reduction in vaginal pH between Baseline and Week 12 was also statistically significant for Imvexxy 4 and 10 mcg inserts. 

Side Effects

The most common adverse effect associated with the use of Imvexxy is headache.

The Imvexxy 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. Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. The Women’s Health Initiative (WHI) estrogen-alone sub-study reported increased risks of stroke and deep vein thrombosis (DVT). The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older. Estrogen Plus Progestin Therapy: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. The WHI estrogen plus progestin sub-study reported increased risks of stroke, DVT, pulmonary embolism (PE) and myocardial infarction (MI). The WHI estrogen plus progestin sub-study reported increased risks of invasive breast cancer. The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older. 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. 

Mechanism of Action

Imvexxy is a bio-identical vaginal estrogen. Endogenous 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 mcg 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 in the peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. To date, two estrogen receptors have been identified. These vary in proportion from tissue to tissue. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH), and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. 

Additional Information

For additional information regarding Imvexxy or moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause, please visit https://imvexxy.com/