Company:

Upsher-Smith

Estrogen

Estradiol 0.25mg, 0.5mg, 1mg; per packet; topical gel.

Moderate to severe vasomotor menopausal symptoms.

The addition of exogenous estrogens helps to alleviate the vasomotor symptoms associated with declining estrogen levels.

Divigel (estradiol 0.1%) is a clear, colorless, alcohol-based gel that is designed to deliver sustained circulating concentrations of estradiol when applied once daily to the skin.

The efficacy of this product in treating vasomotor symptoms in post-menopausal women was evaluated in a 12-week, double-blind, placebo-controlled trial involving 495 patients. Divigel 0.25g, 0.5g, or 1g (corresponding to 0.25mg, 0.5mg, and 1mg estradiol), applied once daily to the thigh, was compared to placebo. At week 4, Divigel at doses of 0.5g and 1g/day resulted in significant reductions in the median daily frequency and the median daily severity of moderate to severe hot flushes compared to placebo; at week 7, treatment with Divigel 0.25g/day also reached statistical significance in improvements in these measurements. The statistically significant reductions in median daily frequency and severity of hot flashes were continued through week 12 for all three Divigel doses compared to placebo.

Apply entire contents of 1 packet once daily to 5” x 7” area of dry intact skin on upper thigh; alternate right and left thigh for daily application. Initially 0.25g (corresponding to 0.25mg estradiol)/day; individualize. Allow gel to dry before dressing; do not wash area for at least 1 hr after application; wash hands after use.

Not applicable.

Undiagnosed abnormal genital bleeding. Breast or other estrogen-dependent neoplasias. Hypercoagulability. Thrombophlebitis or thromboembolic disorders. Hepatic dysfunction or disease. Pregnancy.

Patients with intact uterus should receive a progestin to avoid endometrial hyperplasia. Do initial complete physical and repeat annually (include BP, mammogram, Pap smear). Reevaluate periodically; use lowest effective dose. Endometriosis. Severe hypocalcemia. Bone disease associated with hypercalcemia. Discontinue if jaundice or hypercalcemia occurs, and during immobilization or at least 2 weeks before surgery associated with increased risk of thromboembolism. Hypertriglyceridemia. Porphyria. Hepatic hemangioma. SLE. Discontinue if sudden visual changes occur pending evaluation. Product is flammable. Nursing mothers.

May be potentiated by CYP3A4 inhibitors. May be antagonized CYP3A4 inducers. May be affected by application of sunscreen.

Hypertension, edema, chloasma, mastodynia, headache, glucose intolerance, vaginitis, changes in bleeding patterns, weight changes, intolerance to contact lenses, increased risk of gallbladder disease, thromboembolic events.

Do not allow other persons to contact the area of application for at least 1 hr. If someone else applies the gel, advise them to use plastic disposable gloves. Avoid fire, flame, smoking until after gel has dried completely. Avoid eyes.

Packets—30

For more information call (800) 654-2299 or visit www.Divigelus.com.

8/1/07