Side Effects

Adverse drug reactions occur most commonly during the first months of treatment. They are usually mild and subside with continued treatment. Very rarely skin irritation can occur with DIVIGEL. Using alternate thighs for each dosing is recommended.

The following side effects generally do not require medical attention, and will go away as your body adjusts to DIVIGEL:

Common: headache, breast pain, breast tenderness, bloating, weight increase, nausea/vomiting, abdominal pain (cramping), skin irritation.

Uncommon: migraine, changes in mood.

If you think you are reacting poorly to DIVIGEL or are having other problems, please tell your doctor.

Warnings and Precautions

It should not be used by women with an intact uterus unless it is prescribed in association with a progestin.

This medication should be used only under the supervision of a doctor, with regular follow-up at least once a year to identify side effects associated with its use. Your first follow-up visit should be within 3 to 6 months of starting treatment. Your visit may include a blood pressure check, a breast exam, a Pap smear and pelvic exam. You should have a mammogram before starting treatment and at regular intervals as recommended by your doctor. Your doctor may recommend some blood tests.

Serious Warnings and Precautions

Therefore, you should carefully consider the following:

• There is an increased risk of developing invasive breast cancer, heart attack, stroke and blood clots in both lungs and large veins with the use of estrogen plus progestin therapy.
• There is an increased risk of stroke and blood clots in the large veins with the use of estrogen-alone therapy.
• Estrogens with or without progestins should not be used to prevent heart disease or stroke.
• Estrogens with or without progestins should be used at the lowest effective dose and for the shortest period of time possible. Regular medical follow-up is advised.

Overgrowth of the lining of the uterus and cancer of the uterus:

Ovarian Cancer:

In some studies the use of estrogen-alone therapy and estrogen plus progestin therapies for 5 or more years has been associated with an increased risk of ovarian cancer.

The use of estrogen-alone therapy by post menopausal women who still have a uterus increases the risk of developing endometrial hyperplasia (overgrowth of the lining of the uterus), which increases the risk of endometrial cancer (cancer of the lining of the uterus).

If you plan to take estrogen therapy and you still have your uterus, you should take a progestin medication (another hormone drug) regularly for a certain number of days of each month to reduce the risk of endometrial hyperplasia.

You should discuss progestin therapy and risk factors for endometrial hyperplasia and endometrial carcinoma with your doctor. You should also report any unexpected or unusual vaginal bleeding to your doctor.

If you have had your uterus removed, you are not at risk of developing endometrial hyperplasia or endometrial carcinoma. Progestin therapy is therefore not generally required in women who have had a hysterectomy.

Abnormal Blood Clotting:

The risk of blood clots also increases with age, if you or a family member has had blood clots, if you smoke or if you are severely overweight. The risk of blood clots is also temporarily increased if you are immobilized for long periods of time and following major surgery. You should discuss risk factors for blood clots with your doctor since blood clots can be life-threatening or cause serious disability.

Gallbladder Disease:

The use of estrogens by postmenopausal women has been associated with an increased risk of gallbladder disease requiring surgery.

BEFORE you use, talk to your doctor or pharmacist if you:

• have a history of allergy or intolerance to any medications or other substances
• have a personal history of breast disease (including breast lumps) and/or breast biopsies, or a family history of breast cancer
• have experienced any unusual or undiagnosed vaginal bleeding
• have a history of uterine fibroids or endometriosis
• have a history of liver disease, jaundice (yellowing of the eyes and/or skin) or itching related to estrogen use or during pregnancy
• have a history of migraine headache
• have a history of high blood pressure
• have a personal or family history of blood clots, or a personal history of heart disease or stroke
• have a history of kidney disease, asthma or epilepsy (seizures)
• have a history of bone disease (this includes certain metabolic conditions or cancers that can affect blood levels of calcium and phosphorus)
• have been diagnosed with diabetes
• have been diagnosed with porphyria (a disease of blood pigment)
• have a history of high cholesterol or high triglycerides
• are pregnant or may be pregnant
• have had a hysterectomy (surgical removal of the uterus)
• smoke
• have a thyroid problem (hypothyroidism)