Divigel

Product
Divigel

Approval Date
June 4, 2007

Release Date
August 1, 2007

Company
Upsher-Smith

Class
Estrogen

Indication
Moderate to severe vasomotor menopausal symptoms.

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

Agency Roster
Goble & Associates (professional and DTP)
The Reilly Group (PR)

MarketingStrategy/Execution
Thisnew hormone therapy offers the lowest approved dose of estradiol available forthe treatment of moderate to severe hot flashes associated with menopause,according to the manufacturer. As part of the launch, ad agency Goble &Assoc. helped develop a new patient-facing website, www.DivigelUS.com. Thetransdermal therapy may be attractive to women who have been reluctant to takeolder hormone therapies with higher doses. Another possible selling point isthe green angle: Divigel is derived from plant sources, unlike certain olderestrogen therapies derived from the urine of pregnant mares.

The Market

Physician Outlook
Study planned, 2008

Also in the Pipeline(according to Adis R&D Insights)
Drug: Aprela, CE/BZA
Manufacturer: LigandPharmaceuticals, Wyeth
Indication: Postmenopausal osteoporosis prevention, Vaginalatrophy, Vasomotor symptoms
Active Ingredients: Conjugated estrogens/bazedoxifene
Phase: III
Source: Wolters Kluwer Health, Oct. 2007

Recent MM&MCoverage
Product News

Goble &Associates

Goble &Associates Listing

TheTop 60: Goble & Associates

Pharmacology
The addition of exogenous estrogens helps to alleviate thevasomotor symptoms associated with declining estrogen levels.

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

Clinical Trials
The efficacy of this product in treating vasomotor symptomsin 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 thethigh, was compared to placebo. At week 4, Divigel at doses of 0.5g and 1g/dayresulted in significant reductions in the median daily frequency and the mediandaily severity of moderate to severe hot flushes compared to placebo; at week7, treatment with Divigel 0.25g/day also reached statistical significance inimprovements in these measurements. The statistically significant reductions inmedian daily frequency and severity of hot flashes were continued through week12 for all three Divigel doses compared to placebo.

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

Adults
Apply entire contents of 1 packet once daily to 5” x 7” areaof dry intact skin on upper thigh; alternate right and left thigh for dailyapplication. Initially 0.25g (corresponding to 0.25mg estradiol)/day;individualize. Allow gel to dry before dressing; do not wash area for at least1 hr after application; wash hands after use.

Children
Not applicable.

Contraindications
Undiagnosed abnormal genital bleeding. Breast or otherestrogen-dependent neoplasias. Hypercoagulability. Thrombophlebitis orthromboembolic disorders. Hepatic dysfunction or disease. Pregnancy.

Precautions
Patients with intact uterus should receive a progestin toavoid endometrial hyperplasia. Do initial complete physical and repeat annually(include BP, mammogram, Pap smear). Reevaluate periodically; use lowesteffective dose. Endometriosis. Severe hypocalcemia. Bone disease associatedwith hypercalcemia. Discontinue if jaundice or hypercalcemia occurs, and duringimmobilization or at least 2 weeks before surgery associated with increasedrisk of thromboembolism. Hypertriglyceridemia. Porphyria. Hepatic hemangioma.SLE. Discontinue if sudden visual changes occur pending evaluation. Product isflammable. Nursing mothers.

Interactions
May be potentiated by CYP3A4 inhibitors. May be antagonizedCYP3A4 inducers. May be affected by application of sunscreen.