FEMRING

AbsorptionEstradiol acetate is hydrolyzed to estradiol which is absorbed through the vaginal mucosa as evidenced by the mean time to maximum concentration (t max ) for estradiol of about 1 hour (range 0.25 to 1.5 hrs). After achieving the Cmax the estradiol concentration starts declining during the first 24 to 48 hours and then at a relatively constant rate for the remainder of the 3-month dosing interval (see Figure 1 for results from rings stored for 16 months). In vitro studies have shown th...

14.1 Effects on Vasomotor Symptoms A 13-week double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy of 2 doses of the vaginal ring in the treatment of moderate to severe vasomotor symptoms in 333 postmenopausal women between 29 and 85 years of age (mean age 51.7 years, 77 percent were Caucasian) who had at least 7 moderate to severe hot flushes daily or at least 56 moderate to severe hot flushes per week before randomization. Patients were randomized to receive either placebo, Femring 0.05 mg/day or Femring 0.10 mg/day. Femring 0.05 mg/day and Femring 0.10 mg/da...

The following serious adverse reactions are discussed elsewhere in the labeling:

• Cardiovascular Disorders [see Boxed Warning , Warnings and Precautions (5.1) ].
• Malignant Neoplasms [see Boxed Warning , Warnings and Precautions (5.2) ]. Most common adverse reactions (incidence > 5 percent) are vaginal bleeding and breast tenderness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Millicent at 1-877-810-2101 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experien...

Femring 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 and MI), or a history of these conditions
• Known anaphylactic reaction or an...

Femring is used only in the vagina, however, the risks associated with oral estrogens should be taken into account.

• Estrogens increase the risk of gallbladder disease ( 5.4 )
• Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.5 , 5.6 , 5.9 , 5.10 )
• Monitor thyroid function in women on thyroid replacement therapy ( 5.11 , 5.18 ) 5.1 Cardiovascular Disorders An increased risk of stroke and DVT has been reported with es...

7 DRUG INTERACTIONS No drug interaction studies have been conducted for Femring.

• Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism ( 7.1 ) 7.1 Metabolic Interactions In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CY...