The FDA has granted approval to a generic estradiol gel, 0.06%, manufactured by ANI Therapeutics, for the relief of moderate to severe vasomotor symptoms (hot flashes) and vulvar and vaginal atrophy associated with menopause. This approval provides a more accessible alternative to the reference listed drug, EstroGel Gel, 0.06% (Ascend Therapeutics), initially approved in February 2004.
The estradiol gel is designed for topical application, with a recommended daily dose of 1.25 g (one pump), containing 0.75 mg of estradiol, applied to the arm. The FDA advises that for postmenopausal women with a uterus, prescribing estrogen should be considered alongside progestin to mitigate the risk of endometrial cancer. However, this is not necessary for women without a uterus. In cases where estradiol gel is prescribed solely for vulvar and vaginal atrophy, topical vaginal products should also be considered.
Clinical trial data indicated no measurable transfer of estradiol one hour after application, as shown in a study involving 24 non-dosed postmenopausal women following direct skin contact with subjects administered the gel.
Estradiol, a primary intracellular human estrogen, plays a crucial role in the development and maintenance of the female reproductive system. In normally cycling adult women, the ovarian follicle secretes between 70 to 500 mcg of estradiol daily, depending on the menstrual cycle phase.
A study published in Sexuality, Reproduction, and Menopause involving 890 menopausal women using estradiol gel reported a roughly 75% reduction in hot flash frequency, decreasing from 5.87 to 1.44 hot flashes per day. Additionally, the severity of hot flashes and vaginal dryness decreased by approximately 55% and 50%, respectively. About 75% of respondents reported improvement within 2 weeks, 89% within 3 weeks, and 95% within 4 weeks.
Common adverse events associated with estradiol gel include headache, flatulence, and breast pain or tenderness. Other potential adverse effects include stomach cramps, bloating, nausea, vomiting, hair loss, fluid retention, and vaginal yeast infection. Serious adverse events may include cardiovascular disorders, such as stroke, coronary heart disease, and venous thromboembolism, as well as malignant neoplasms like endometrial, breast, and ovarian cancers. Application site reactions were reported in approximately 0.6% of patients in controlled clinical trials.
According to IQVIA data from August 2024, US annual sales for estradiol gel were approximately $16.7 million. The availability of a generic option is expected to provide a more affordable treatment for patients.
Nikhil Lalwani, president and CEO of ANI Pharmaceuticals, stated, "With the FDA approval and commercialization of estradiol gel, 0.06%, we are pleased to bring another limited-competition product to market and ensure that customers and patients in need have ready access."
