Divigel 0.75 mg/packet (for the skin) is used to treat certain symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation.

Divigel 0.75 mg/packet may also be used for purposes not listed in this medication guide.

You should not use this medicine if you have: undiagnosed vaginal bleeding, liver disease, bleeding problems, an increased risk of blood clots, if you will have major surgery, or if you have ever had a heart attack, a stroke, a blood clot, or cancer of the breast, uterus/cervix, or vagina.

Do not use if you are pregnant.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Report any unusual vaginal bleeding right away.

Using this medicine can increase your risk of blood clots, stroke, heart attack, or cancer of the breast, uterus, or ovaries. Estradiol should not be used to prevent heart disease, stroke, or dementia.

Divigel 0.75 mg/packet is absorbed through the skin and can cause side effects in a child who comes into contact with the skin where you have applied the medicine.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Use the medicine at the same time each day.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

Wash your hands with soap and water after applying the medicine. Do not allow other people to get this medicine on their skin. If this happens, wash the area thoroughly with soap and water.

Do not allow a child to come into contact with the skin where you have applied Divigel 0.75 mg/packet. Topical estradiol is absorbed through the skin and can cause premature puberty in a child who comes into contact with this medicine. Cover treated areas with clothing to protect others from coming into contact with the skin where you apply this medicine.

If you need major surgery or will be on long-term bed rest, you may need to stop using this medicine for a short time. Any doctor or surgeon who treats you should know that you are using estradiol.

Estradiol may increase your risk of developing a condition that can lead to uterine cancer. To help lower this risk, your doctor may also want you to take a progestin. Report any unusual vaginal bleeding right away.

Your doctor should check your progress on a regular basis to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using Divigel 0.75 mg/packet.

Store at room temperature away from moisture and heat.

Divigel 0.75 mg/packet may be flammable. Do not use near high heat or open flame. Do not smoke until the medicine has completely dried on your skin.

You should not use estradiol if you are allergic to it, or if you have:

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

• liver disease;

• a history of heart attack, stroke, or blood clot;

• an increased risk of having blood clots due to a heart problem or a hereditary blood disorder; or

• a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina.

Do not use estradiol if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using estradiol can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Divigel 0.75 mg/packet should not be used to prevent heart disease, stroke, or dementia. Divigel 0.75 mg/packet may actually increase your risk of developing these conditions.

Tell your doctor if you have ever had:

• heart disease;

• liver problems, or jaundice caused by pregnancy or taking hormones;

• kidney disease;

• gallbladder disease;

• asthma;

• epilepsy or other seizure disorder;

• migraines;

• lupus;

• endometriosis or uterine fibroid tumors;

• hereditary angioedema;

• porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

• a thyroid disorder; or

• high levels of calcium in your blood.

Using estradiol may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Estradiol lowers the hormone needed to produce breast milk and can slow breast milk production. Tell your doctor if you are breastfeeding.

Use the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 12 hours. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include nausea, vomiting, stomach pain, breast tenderness, drowsiness, and vaginal bleeding.

Avoid getting Divigel 0.75 mg/packet in your eyes. If this does happen, rinse with water.

Wait at least 25 minutes after applying Divigel 0.75 mg/packet before you apply sunscreen to the same skin area.

Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using estradiol.

Grapefruit may interact with estradiol and lead to unwanted side effects. Avoid the use of grapefruit products.

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

Divigel 0.75 mg/packet may cause serious side effects. Call your doctor at once if you have:

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

• signs of a blood clot--sudden numbness or weakness, sudden vision loss, slurred speech, stabbing chest pain, coughing up blood, pain or warmth in one or both legs;

• swelling or tenderness in your stomach, severe stomach pain spreading to your back, nausea and vomiting;

• jaundice (yellowing of the skin or eyes);

• memory problems, confusion, unusual behavior;

• unusual vaginal bleeding, pelvic pain;

• a lump in your breast; or

• high calcium levels--confusion, tiredness, nausea, vomiting, loss of appetite, constipation, increased thirst or urination, weight loss.

Topical estradiol is absorbed through the skin of a child who comes into contact with Divigel 0.75 mg/packet. Call your doctor if a child in close contact with you develops swollen nipples or enlarged breasts.

Common side effects of Divigel 0.75 mg/packet may include:

• nausea, vomiting, stomach cramps;

• bloating, swelling, weight gain;

• breast pain or tenderness;

• headache;

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

• thinning scalp hair; or

• cold symptoms such as stuffy nose, sneezing, sore throat.

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.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can affect estradiol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any medicine you start or stop using.