Divigel 0.5 mg / packet for use on skin

You should not use estradiol topical if you have:

• abnormal vaginal bleeding that has not been checked by a doctor;

• any type of breast, uterine, or hormone-dependent cancer;

• a history of heart attack, stroke, or blood clot (especially in your lung or your lower body);

• liver disease;

• a bleeding or blood-clotting disorder;

• if you are pregnant or may become pregnant; or

• if you have ever had an allergic reaction to estradiol topical.

Estradiol will not prevent heart disease, heart attack, stroke, breast cancer, or dementia, and may actually increase your risk of developing these conditions. Estradiol may also increase your risk of uterine or ovarian cancer. Talk with your doctor about your individual risks.

To make sure estradiol topical is safe for you, tell your doctor if you have:

• unusual vaginal bleeding;

• heart disease;

• asthma;

• epilepsy or other seizure disorder;

• liver or kidney disease;

• hereditary angioedema;

• endometriosis;

• a thyroid disorder;

• lupus;

• high levels of calcium in your blood (hypercalcemia);

• migraines;

• gallbladder disease; or

• risk factors for coronary artery disease (such as diabetes, smoking, being overweight, having high blood pressure or high cholesterol, having a family history of coronary artery disease, being older than 40, or if you have had a hysterectomy).

Do not use estradiol topical if you are pregnant. Use effective birth control to prevent pregnancy while you are using this medicine.

Estradiol can pass into breast milk and may harm a nursing baby. This medicine may also slow breast milk production. Do not use if you are breast-feeding a baby.

Use the missed dose as soon as you remember. If you are more than 12 hours late, skip the missed dose. Do not use extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using estradiol topical and call your doctor at once if you have:

• abnormal vaginal bleeding;

• a lump in your breast;

• confusion, problems with memory or concentration;

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

• signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood; or

• signs of a blood clot in your leg--pain, swelling, warmth, or redness in one or both legs.

Topical estradiol is absorbed through the skin of a child who comes into contact with this medicine. Call your doctor if a child who has close contact with you develops swollen nipples or enlarged breasts.

Common side effects may include:

• breast pain;

• headache;

• vaginal itching or discharge, changes in your menstrual periods, light vaginal bleeding or spotting;

• thinning scalp hair; or

• nausea, vomiting, bloating, stomach cramps.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with estradiol topical, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.