Divigel

Divigel is a prescription medication used to treat symptoms of menopause including hot flashes. 

Divigel contains estradiol which is a form of the hormone estrogen. It replaces estrogen that is not naturally produced by the ovaries.

This medication comes as a gel. It is usually applied to the left or right upper thigh daily. 

Common side effects of Divigel include breast tenderness and irregular vaginal bleeding or spotting.

Divigel is a prescription medication used to treat symptoms of menopause including hot flashes. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Upsher-Smith Laboratories, Inc.

Serious side effects have been reported with Divigel. See the “Divigel Precautions” section.

Common side effects of Divigel include the following:

• Headache
• Breast pain/tenderness
• Irregular vaginal bleeding or spotting
• Stomach or abdominal cramps, bloating
• Nausea and vomiting
• Hair loss
• Fluid retention
• Vaginal yeast infection

This is not a complete list of Divigel side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Amiodarone (Cordarone, Pacerone)
• Antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral)
• Aprepitant (Emend)
• Carbamazepine (Carbatrol, Epitol, Tegretol)
• Cimetidine (Tagamet)
• Clarithromycin (Biaxin)
• Cyclosporine (Neoral, Sandimmune)
• Dexamethasone (Decadron, Dexpak)
• Diltiazem (Cardizem, Dilacor, Tiazac, others)
• Erythromycin (E.E.S, Erythrocin)
• Fluoxetine (Prozac, Sarafem)
• Fluvoxamine (Luvox)
• Griseofulvin (Fulvicin, Grifulvin, Gris-PEG)
• Lovastatin (Altocor, Mevacor)
• Medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase)
• Medications for thyroid disease
• Nefazodone
• Other medications that contain estrogen
• Phenobarbital
• Phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin)
• Rifampin (Rifadin, Rimactane, in Rifamate)
• Sertraline (Zoloft)
• Troleandomycin (TAO)
• Verapamil (Calan, Covera, Isoptin, Verelan)
• Zafirlukast (Accolate)
• St. John's Wort

This is not a complete list of Divigel drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Divigel including the following:

• bulging eyes
• yellowing of the skin or eyes
• itching
• loss of appetite
• fever
• joint pain
• stomach tenderness, pain, or swelling
• movements that are difficult to control
• hives
• rash or blisters on the skin
• swelling, of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
• hoarseness
• wheezing
• difficulty breathing or swallowing

Do not use Divigel if you:

• are allergic to Divigel or to any of its ingredients or have a known history of angioedema to Divigel
• have abnormal vaginal bleeding
• have a known or suspected history of breast cancer
• have a known or suspected estrogen-dependent cancer
• currently have or have a history of blood clots
• have had a heart attack or stroke
• have been diagnosed with a bleeding disorder
• have liver disease
• are pregnant or possibly pregnant

Grapefruit and grapefruit juice may interact with Divigel and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Before using Divigel, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Divigel or to any of its ingredients or have a known history of angioedema to Divigel
• have abnormal vaginal bleeding
• currently have or have had certain cancers 
• currently have or have a history of blood clots
• have had a heart attack or stroke
• have been diagnosed with a bleeding disorder
• have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine; endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
• If you are going to have surgery or will be on bedrest
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

Divigel should not be used during pregnancy. There appears to be little or no increased risk of birth defects in children born to women who inadvertently used estrogens during early pregnancy. Talk to your doctor right away if you become pregnant while using Divigel.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Divigel should not be used during lactation. Estrogen has been detected in human breast milk. Estrogen can decrease the quality or quantity of breast milk. Caution should be taken if Divigel is given to a nursing mother. 

Use Divigel exactly as prescribed.

• Divigel should be applied once a day, around the same time each day
• Apply Divigel to clean, dry, and unbroken (without cuts or scrapes) skin. If you take a bath or shower, be sure to apply your Divigel after your skin is dry. The application site should be completely dry before dressing or swimming
• Apply Divigel to either your left or right upper thigh. Change between your left and right upper thigh each day to help prevent skin irritation

TO APPLY:

Step 1: Wash and dry your hands thoroughly.

Step 2: Sit in a comfortable position.

Step 3: Cut or tear the Divigel packet

Step 4: Using your thumb and index finger, squeeze the entire contents of the packet onto the skin of the upper thigh 

Step 5: Gently spread the gel in a thin layer on your upper thigh over an area of about 5 by 7 inches, or two palm prints. It is not necessary to massage or rub in Divigel.

Step 6: Allow the gel to dry completely before dressing.

Step 7: Dispose of the empty Divigel packet in the trash.

Step 8: Wash your hands with soap and water immediately after applying Divigel to remove any remaining gel and reduce the chance of transferring Divigel to other people.

Important things to remember when using Divigel

• Wash your hands with soap and water after applying the gel to reduce the chance that the medicine will be spread from your hands to other people
• Allow the gel to dry before dressing. Try to keep the area dry for as long as possible
• Do not allow others to come in contact with the area of skin where you applied the gel for at least one hour after you apply Divigel
• You should not allow others to apply the gel for you. However, if this is necessary, the individual should wear a disposable plastic glove to avoid direct contact with Divigel
• Do not apply Divigel to your face, breast, or irritated skin
• Never apply Divigel in or around the vagina
• Divigel contains alcohol. Alcohol based gels are flammable. Avoid fire, flame or smoking until the gel has dried.

If you miss a dose, do not double the dose on the next day to catch up. If your next dose is less than 12 hours away, it is best just to wait and apply your normal dose the next day. If it is more than 12 hours until the next dose, apply the dose you missed and resume your normal dosing the next day. Do not apply Divigel more than once each day. If you accidentally spill some of the contents of a Divigel packet, do not open a new packet. Wait and apply your normal dose the next day.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication

The recommended dose range of Divigel (estradiol) transdermal gel for the treatment of menopause symptoms is 0.25 g to 1.0 grams daily to the right or left upper thigh.

If you apply too much Divigel, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store Divigel at 20 to 25°C (68 to 77°F).
• Keep this and all medicines out of the reach of children.

WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA

Estrogen-Alone Therapy

• There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens
• Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia
• The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT)
• The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older 

Estrogen Plus Progestin Therapy

• Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia 
• The WHI estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism (PE), and myocardial infarction (MI) 
• The WHI estrogen plus progestin study reported increased risks of invasive breast cancer 
• The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older