IMVEXXY Safety & PK Data

Go Low: Discover the Outcome of the

Lowest Effective Dose of Vaginal 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.

Both doses of IMVEXXY resulted in average systemic estradiol levels that were within the normal postmenopausal range (n=54)1,3,4

Chart: IMVEXXY vs placebo mean estradiol plasma concentration over 24 hours at day 14

PK Substudy Design

PK Substudy Design

A substudy of the REJOICE trial (N=54) evaluated the pharmacokinetics (PK) of IMVEXXY 4-mcg and 10-mcg doses once daily for 2 weeks followed by twice weekly for 10 weeks.3

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

Chart: IMVEXXY vs Vagifem mean estradiol plasma concentration over 24 hours after single dose

Systemic absorption AUC (0-24 Hours) and Cmax (0-24 Hours) were lower with IMVEXXY relative to Vagifem*

*IMVEXXY vs Vagifem: AUC0-24 pg-h/mL P<0.0001; Cmax pg/mL P=0.0194.

AUC = area under the curve.

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

IMVEXXY PK vs Vagifem study design

IMVEXXY PK vs Vagifem study design

A phase 1, randomized, single-dose, open-label, 2-way crossover relative bioavailability study was undertaken to compare 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 trial lasting 12 weeks (N=574)1,6

Female Reproductive Icon

IMVEXXY demonstrated no cases endometrial hyperplasia6

In a clinical trial, no diagnoses of endometrial hyperplasia or malignancy from endometrial biopsies were observed at week 12. Long-term studies are required to assess the risk associated with continued use.6

Shield Icon

IMVEXXY had a low incidence of adverse reactions1

  • In a double-blind, placebo-controlled trial, adverse events with an incidence of ≥3% in any IMVEXXY group and numerically greater than those reported in the placebo group included headache, with rates of 3.7% for the 4-mcg dose and 2.6% for the 10-mcg dose vs 3.1% in the placebo group1

  • When counseling patients, please consider estrogen class risks included in the boxed warning and described further in the patient labeling information

Safety Study Design

Safety Study Design

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

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.


Important Safety Information

Warning: endometrial cancer, cardiovascular disorders, breast cancer and probable dementia

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
  • Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia
  • 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

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 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

Contraindications

  • IMVEXXY® 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 or a history of these conditions; known anaphylactic reaction or angioedema to IMVEXXY; known liver impairment or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

Warning and Precautions

  • IMVEXXY is intended only for vaginal administration. Systemic absorption may occur with the use of IMVEXXY.
  • 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, severe hypertriglyceridemia or cholestatic jaundice.
  • Estrogen therapy may cause an exacerbation of 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 (incidence ≥3 percent) and greater than placebo was headache.

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

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