The FDA has approved Imvexxy (estradiol vaginal inserts, TherapeuticsMD) to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause.1
VVA occurs as the body’s estrogen levels decline during menopause, causing vaginal tissue to become dry, less elastic, and thin. About 32 million women in the United States. are affected by VVA.2
Pharmacology and Pharmacokinetics
Imvexxy exerts its effect through re-estrogenizing tissue in and around the vagina. Both the 4 and 10 mcg doses display mean serum concentrations of estradiol and estrone that are within average postmenopausal range.2
Dose and Administration
Imvexxy should be administered intravaginally once daily at about the same time for 2 weeks, followed by 1 insert twice weekly. Generally, the dose should be initiated at 4 mcg, with dose adjustments based on clinical response.1
The effectiveness and safety of Imvexxy was evaluated in a 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 574 postmenopausal women between 40 and 75 years old who reported moderate to severe dyspareunia as their most bothersome symptom of VVA. The group using Imvexxy demonstrated a statistically significant reduction in the severity of moderate to severe dyspareunia compared with the placebo group. The Imvexxy group also displayed statistically significant changes in pH and vaginal cytology.1,2
Contraindications, Warnings, and Precautions
Imvexxy carries a boxed warning of the risks associated with both estrogen alone and estrogen plus progestin therapy. Regarding estrogen alone therapy, the boxed warning states that there is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogen; it should not be used for the prevention of cardiovascular disease or dementia; that the Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of deep vein thrombosis (DVT) and stroke; and that the WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 and older. Regarding estrogen plus progestin therapy, the boxed warning says that it should not be used for the prevention of cardiovascular disease or dementia; that the WHI estrogen plus progestin substudy reported increased risks of DVT, myocardial infarction (MI), pulmonary embolism (PE), and stroke; that the WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer; and that the WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 and older. The boxed warning says that estrogen therapy, either with or without progestin, should be used at the lowest effective dose and for the shortest possible duration that is consistent with the treatment goals and risks for each patient.
The use of Imvexxy is contraindicated in patients with anaphylactic reaction or angioedema with Imvexxy; active or a history of arterial thromboembolic disease (for example, stroke and MI); active or a history of DVT or PE; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; liver impairment or disease; protein C, protein S, or antithrombin deficiency, or other thrombophilic disorders; and undiagnosed abnormal genital bleeding.
Treatment with estrogen increases the risk of gallbladder disease. The use of estrogen should be discontinued if cholestatic jaundice, loss of vision, severe hypercalcemia or severe hypertriglyceridemia occurs. Patients using thyroid replacement hormone therapy should have their thyroid function monitored. CYP3A4 inducers or inhibitors may affect estrogen drug metabolism, resulting in decreased or increased estrogen plasma concentrations.
The most common adverse effect is headache.1
Monica Holmberg, PharmD, BCPS, earned her PharmD at the University of Connecticut in Storrs and completed an ambulatory care residency at the Phoenix VA Healthcare System in Arizona. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix.
1. Imvexxy [prescribing information]. Boca Raton, FL: TherapeuticsMD, Inc. 2018. accessdata.fda.gov/drugsatfda_docs/label/2018/208564s000lbl.pdf.Accessed June 6, 2018.
2.TherapeuticsMD announces FDA approval of TX-004HR: IMVEXXY (estradiol vaginal inserts), the lowest dose vaginal estrogen product approved for the treatment of moderate to severe dyspareunia, a symptom of VVA, due to menopause [news release]. Boca Raton, FL: May 30, 2018. ir.therapeuticsmd.com/news-releases/news-release-details/therapeuticsmd-announces-fda-approval-tx-004hr-imvexxytm#.Accessed June 6, 2018.