IMPORTANT SAFETY INFORMATION

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER

See full prescribing information for complete boxed warning.

Estrogen-Alone Therapy

Estrogen Plus Progestin Therapy

Contraindications

IMVEXXY (estradiol vaginal inserts) is contraindicated in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, PE, or history of these conditions; active arterial thromboembolic disease (for example stroke, MI) or a history of these conditions; known anaphylactic reaction, angioedema, or hypersensitivity to IMVEXXY; known liver impairment or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

Warning and Precautions

Adverse Reactions

Indication

IMVEXXY (estradiol vaginal inserts) is an estrogen indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

Please note that this information is not comprehensive. Please click here for the Full Prescribing Information, including BOXED WARNING.

Full Safety Information Full Prescribing Information, Including BOXED WARNING
For US Healthcare Professionals Patient Site
Full Safety Information Full Prescribing Information, Including BOXED WARNING Patient Site

Only IMVEXXY offers an
ultra-low dose (4 mcg)

of bioidentical estradiol1,2,*

The clinical relevance of systemic absorption rates for all vaginal estrogen therapies is not known. Systemic absorption may occur with IMVEXXY. The risks associated with systemic estrogen therapy should be considered.1

Both doses of IMVEXXY resulted in average systemic estradiol levels that were within the normal postmenopausal range (n=54).1,3

A substudy of the REJOICE trial (n=54) evaluated the pharmacokinetics (PK) of IMVEXXY 4 mcg and
10 mcg once daily for 2 weeks followed by twice weekly for 10 weeks.1

*Bioidentical hormones are defined as substances that have exactly the same chemical and molecular structure as hormones that are produced in the human body.4 The relevance of risks associated with the use of synthetic hormones compared with bioidentical hormones is unknown.

IMVEXXY 10 mcg had lower systemic absorption levels vs VAGIFEM® 10 mcg (n=35).5

Systemic absorption AUC (0-24 hours) and Cmax (0-24 hours) were lower with IMVEXXY relative to VAGIFEM.5,†

†IMVEXXY vs VAGIFEM: AUC0-24 pg-h/mL, P<0.0001; Cmax pg/mL, P=0.0194.

AUC=area under the curve; Cmax=maximum concentration.

VAGIFEM is a registered trademark of Novo Nordisk Health Care AG.

†IMVEXXY vs VAGIFEM: AUC0-24 pg-h/mL, P<0.0001; Cmax pg/mL, P=0.0194.

AUC=area under the curve; Cmax=maximum concentration.

VAGIFEM is a registered trademark of Novo Nordisk Health Care AG.

Two randomized, single‑dose, open-label, 2‑way crossover, relative bioavailability studies were undertaken to compare the pharmacokinetics (PK) of 10‑mcg IMVEXXY with that of an approved vaginal estradiol insert, 10‑mcg VAGIFEM.5

A comprehensive safety and tolerability profile

The safety of IMVEXXY 4 mcg and 10 mcg was assessed in a phase 3 study lasting 12 weeks (N=574).1

No cases of endometrial hyperplasia

IMVEXXY demonstrated no cases of endometrial hyperplasia with either dose in a 12‑week clinical trial.6,‡

‡Long-term studies are required to assess the risk associated with continued use. See BOXED WARNING about the risk of endometrial cancer.

Low incidence of adverse reactions

Please review the Full Prescribing Information, including BOXED WARNING, for the risk information about IMVEXXY. The most common adverse reaction with IMVEXXY (≥3% and greater than placebo) was headache.1

The safety of IMVEXXY 4 mcg and 10 mcg was assessed in a single, double‑blind, parallel-group, placebo‑controlled study (N=574). The duration of treatment in this study was 12 weeks. Most of the women (>90%) completed the 12 weeks of treatment. The only adverse reactions reported in the label are those occurring at rates of ≥3% and greater than placebo.1,6

References: 1. IMVEXXY [package insert]. Raleigh, NC: Mayne Pharma; 2023. 2. Data on file. Mayne Pharma. Post-marketing Noninterventional Study report: IMVEXXY® PMR3483-1. 3. Archer DF, Constantine GD, Simon JA, et al; REJOICE Study Group. TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol. Menopause. 2017;24(5):510-516. 4. Stuenkel CA. Compounded bioidentical hormone therapy: new recommendations from the 2020 National Academies of Sciences, Engineering, and Medicine. Menopause. 2021;28(5):576-578. 5. Pickar JH, Amadio JM, Bernick BA, Mirkin S. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule. Climacteric. 2016;19(2):181-187. 6. Constantine GD, Simon JA, Pickar JH, et al; REJOICE Study Group. The REJOICE trial: a phase 3 randomized, controlled trial evaluating the safety and efficacy of a novel vaginal estradiol soft-gel capsule for symptomatic vulvar and vaginal atrophy. Menopause. 2017;24(4):409-416.

IMPORTANT SAFETY INFORMATION

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER

See full prescribing information for complete boxed 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 (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
  • 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 stroke, DVT, pulmonary embolism (PE) 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 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

Contraindications

IMVEXXY (estradiol vaginal inserts) is contraindicated in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, PE, or history of these conditions; active arterial thromboembolic disease (for example stroke, MI) or a history of these conditions; known anaphylactic reaction, angioedema, or hypersensitivity to IMVEXXY; known liver impairment or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

Warning and Precautions

  • Risks from systemic absorption. IMVEXXY is intended only for vaginal administration. Systemic absorption may occur with the use of IMVEXXY.
  • Cardiovascular disorders, malignant neoplasms, and probable dementia.
Please refer to Boxed Warning for endometrial cancer, cardiovascular disorders, probable dementia, and breast cancer.
    • The use of estrogen-alone and estrogen plus progestin therapy has been reported to result in an increase in abnormal mammograms requiring further evaluation.
    • The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. A meta-analysis of
17 prospective and
35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown.
  • Other warnings include:
gallbladder disease; severe hypercalcemia, loss of vision, elevated blood pressure, severe hypertriglyceridemia, cholestatic jaundice, fluid retention, and hypocalcemia in women with hyperparathyroidism.
  • Estrogen therapy may exacerbate:
hypothyroidism, endometriosis, hereditary angioedema, asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas, and should be used with caution in women with these conditions.
    • Women on thyroid replacement therapy should have their thyroid function monitored.

Adverse Reactions

  • The most common adverse reaction with IMVEXXY (≥3%) was headache.

Indication

IMVEXXY (estradiol vaginal inserts) is an estrogen indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

Please note that this information is not comprehensive. Please click here for the Full Prescribing Information, including BOXED WARNING.

IMPORTANT SAFETY INFORMATION

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA and BREAST CANCER

See full prescribing information for complete boxed warning.

Estrogen-Alone Therapy

Estrogen Plus Progestin Therapy