Divigel (estradiol gel) is a clear, colorless gel, which is odorless when dry. Estradiol is a form of estrogen, a female sex hormone that regulates many processes in the body. Divigel is used to treat certain symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation.

Divigel may also be used for purposes not listed in this medication guide.

Use Divigel exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Your doctor may prescribe a progestin to take while you are using estradiol, to help lower this risk. Report any unusual vaginal bleeding right away.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

• Apply Divigel only to clean, dry, unbroken skin. Do not apply to skin that is red or irritated.
• The entire contents of a unit dose packet should be applied each day. To avoid potential skin irritation, Divigel should be applied to the right or left upper thigh on alternating days.
• Divigel should not be applied on the face, breasts, or irritated skin or in or around the vagina. Contact of the gel with eyes should be avoided.
• After application, the gel should be allowed to dry before dressing. The application site should not be washed within 1 hour after applying Divigel.
• Divigel contains alcohol. Alcohol based gels are flammable. Avoid fire, flame or smoking until the gel has dried.
• Wash your hands with soap and water after applying the gel or emulsion. Avoid allowing other people to get Divigel on their skin. If this happens, wash the area thoroughly with soap and water.

Children should avoid coming into contact with skin areas where you have applied Divigel. Topical estradiol is absorbed through the skin and can cause premature puberty in a child who comes into contact with this medicine or with skin where Divigel was applied. Cover treated areas with clothing to protect others from coming into contact with the skin where you apply this medicine.

Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using estradiol.

If you need surgery or medical tests or if you will be on 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.

Store Divigel at room temperature away from moisture and heat.

You should not use Divigel 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 Divigel 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 Divigel if you are pregnant. Use effective birth control to prevent pregnancy while you are using Divigel.

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

Nausea/vomiting, bloating, breast tenderness, headache, or weight changes may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), increased or new vaginal irritation/itching/odor/discharge, severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, increased thirst/urination.

This medication may rarely cause serious problems from blood clots (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism). Get medical help right away if you have any serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of the body, confusion, slurred speech, sudden vision changes (such as partial/complete blindness), pain/redness/swelling of legs, tingling/weakness/numbness in the arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.

A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• abnormal vaginal bleeding
• blood vessel disease or blood clots
• breast, cervical, endometrial, ovarian, liver, or uterine cancer
• dementia
• diabetes
• gallbladder disease
• heart disease or recent heart attack
• high blood pressure
• high cholesterol
• high level of calcium in the blood
• hysterectomy
• kidney disease
• liver disease
• migraine headaches
• protein C deficiency
• protein S deficiency
• stroke
• systemic lupus erythematosus (SLE)
• tobacco smoker
• thyroid disease
• an unusual or allergic reaction to estrogens, other hormones, soy, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This medicine is for external use only. Follow the directions that come with your prescription. Spread the gel into a thin layer. It is not necessary to rub or massage the gel into the skin. Wash your hands with soap and water after applying the gel. Allow the gel to dry for up to 5 minutes before dressing. Avoid fire, flame or smoking until gel has dried. Do not apply to the breast, face or in or around the vagina. Do not use your medicine more often than directed.

A patient package insert for the product will be given with each prescription and refill. Read this sheet carefully each time. The sheet may change frequently.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

What if I miss a dose?

If you miss a dose, use it as soon as you can. If it is almost time for your next dose, use only that dose. Do not use double or extra doses.