DIVIGEL

Divigel Generic Name & Formulations

Legal Class

General Description

Estradiol 0.25mg, 0.5mg, 0.75mg, 1mg, 1.25mg; per packet; topical gel.

Pharmacological Class

Estrogen.

How Supplied

Packets—30

Manufacturer

Vertical Pharmaceuticals

Generic Availability

Mechanism of Action

Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, LH and FSH, through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women

Divigel Indications

Indications

Moderate to severe vasomotor symptoms of menopause.

Divigel Dosage and Administration

Adult

Apply contents of 1 packet once daily to 5" x 7" area of dry skin on upper thigh; alternate thighs daily. Initially 0.25g/day; individualize. Allow gel to dry before dressing; do not wash area for at least 1 hr after application; wash hands after use.

Children

Not applicable.

Administration

Apply contents of 1 packet once daily to 5" x 7" area of dry skin on upper thigh; alternate thighs daily. Allow gel to dry before dressing; do not wash area for at least 1 hr after application; wash hands after use. Do not apply on the face, breasts, or irritated skin or in or around the vagina. Avoid contact with eyes.

Nursing Considerations

Contents of 1 packet should be applied once daily to 5" x 7" area of dry skin on upper thigh; alternate thighs daily. Allow gel to dry before dressing; area should not be washed for at least 1 hr after application; hands should be washed after use. Avoid skin contact with other subjects until the gel is completely dried. Site of application should be covered (clothed) after drying. Do not apply on the face, breasts, or irritated skin or in or around the vagina. Avoid contact with eyes. May be affected by application of sunscreen and other topical lotions. Product is flammable.

Divigel Contraindications

Contraindications

Undiagnosed abnormal genital bleeding. Breast or other estrogen-dependent neoplasms. Thromboembolic disorders (eg, DVT, PE, stroke, MI). Protein C, protein S, or antithrombin deficiency, or other thrombophilias. Hepatic impairment or disease.

Divigel Boxed Warnings

Boxed Warning

Endometrial cancer. Breast cancer. Cardiovascular disorders. Probable dementia.

Divigel Warnings/Precautions

Warnings/Precautions

Increased risk of endometrial carcinoma or hyperplasia in women with intact uterus (adding progestin is essential). Not for prevention of cardiovascular disease or dementia. Increased risk of cardiovascular events (eg, MI, stroke, VTE); discontinue if occurs. Manage risk factors for cardiovascular disease and venous thromboembolism appropriately. Discontinue at least 4–6 weeks before surgery type associated with increased risk of thromboembolism or during prolonged immobilization. Increased risk of breast or ovarian cancer. Risk of probable dementia in women >65yrs of age. Gallbladder disease. Severe hypercalcemia in breast cancer or bone metastases. Visual abnormalities. History of hypertriglyceridemia. Discontinue if cholestatic jaundice, pancreatitis, or hypercalcemia. Permanently discontinue if papilledema or retinal vascular lesions occur. Monitor thyroid function. Conditions aggravated by fluid retention. Hypoparathyroidism. Endometriosis. Hereditary angioedema. Asthma. Diabetes. Epilepsy. Migraine. Porphyria. SLE. Hepatic hemangiomas. Do initial complete physical and repeat annually (include Pap smear, mammogram, and BP). Flammable. Reevaluate periodically. Pregnancy: not indicated. Nursing mothers.

Divigel Pharmacokinetics

Absorption

Cmax: 14 pg/mL for 0.25 g; 28.4 pg/mL for 0.5 g; 51.5 pg/mL for 1.0 g.
Median Tmax: 16 hours (range: 0, 72) for 0.25 g; 10 hours (range: 0, 72) for 0.5 g; 8 hours (range: 0, 48) for 1.0 g.
Steady-state serum concentration is reached by day 12.

Distribution

Estrogens circulate in the blood largely bound to SHBG and albumin.

Metabolism

Hepatic.

Elimination

Renal. Half-life: ~10 hours.

Divigel Interactions

Interactions

May be potentiated by CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice). May be antagonized CYP3A4 inducers (eg, phenobarbital, carbamazepine, rifampin, St. John's wort). Concomitant thyroid replacement; may need to increase thyroid dose. May be affected by application of sunscreen or topical lotions. May interfere with lab tests (eg, thyroid, PT, coagulation factors, glucose tolerance, HDL/LDL, triglycerides, hormone concentrations, other binding or plasma proteins).

Divigel Adverse Reactions

Adverse Reactions

Metrorrhagia, breast tenderness, vaginal mycosis, nasopharyngitis, upper respiratory tract infection; thromboembolism, neoplasms.

Divigel Clinical Trials

See Literature

Divigel Note

Not Applicable

Divigel Patient Counseling