Divigel
Estradiol gel (Divigel) is a hormone replacement therapy used to treat symptoms of menopause, such as hot flashes and night sweats. It comes as single-use packets, and the dose is applied to the skin on your upper thigh once a day. The gel is available as both a brand-name and a generic medication. Common side effects include vaginal yeast infections, breast tenderness, and abnormal vaginal bleeding.
What is Estradiol gel (Divigel)?
What is Estradiol gel (Divigel) used for?
- Hot flashes and night sweats due to menopause
How Estradiol gel (Divigel) works
Drug facts
Side effects of Estradiol gel (Divigel)
The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.
Common Side Effects
- Abnormal vaginal bleeding (4-10%)
- Breast tenderness (3-9%)
- Common cold symptoms (4-6%)
- Upper respiratory tract infection (2-6%)
- Vaginal yeast infection (1-6%)
Less Common Side Effects
- Absence of or painful menstrual periods
- Enlargement of breasts
- Pounding heartbeat
- Passing gas
- Itchy rash
- Tremor
- Joint pain
- Tiredness
- Trouble sleeping
- Muscle spasms
- Weight gain
Estradiol gel (Divigel) serious side effects
Contact your healthcare provider immediately if you experience any of the following.
- Heart attack: chest pain, cold sweats, left arm pain, difficulty breathing
- Stroke: sudden weakness on one side of your body, bad headaches, trouble breathing, or changes in your speech or vision
- Blood clot: chest pain, shortness of breath, dizziness, fast heart rate, swelling, pain, or redness in the arms or legs
- Cancer: lumps, pain, swelling, or changes in the breasts; swollen lymph nodes, unusual or heavy vaginal bleeding, bloating, extreme tiredness, stomach-area pain
The following Estradiol gel (Divigel) side effects have also been reported
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Incidence not known
Abdominal or stomach cramps or pain
acid or sour stomach
backache
belching
blistering, peeling, or loosening of the skin
blurred vision
breast tenderness, enlargement, pain, or discharge
change in vaginal discharge
changes in skin color
changes in vision
chest pain or discomfort
chills
clay-colored stools
clear or bloody discharge from the nipple
confusion
convulsions
darkening of the urine
difficulty with breathing
difficulty with swallowing
dimpling of the breast skin
dizziness or lightheadedness
double vision
fainting
fast heartbeat
fluid-filled skin blisters
full or bloated feeling or pressure in the stomach
headache
headache, severe and throbbing
indigestion
inverted nipple
irregular heartbeat
itching of the vagina or genital area
joint or muscle pain
large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
light-colored stools
loss of appetite
loss of bladder control
lump in the breast or under the arm
migraine headache
mood or mental changes
muscle cramps in the hands, arms, feet, legs, or face
muscle spasm or jerking of all extremities
noisy breathing
numbness and tingling around the mouth, fingertips, or feet
pain during sexual intercourse
pain in the ankles or knees
pain or discomfort in the arms, jaw, back, or neck
pain or feeling of pressure in the pelvis
pain, redness, or swelling in the arm, foot, or leg
painful, red lumps under the skin, mostly on the legs
pains in the stomach, side, or abdomen, possibly radiating to the back
persistent crusting or scaling of the nipple
poor insight and judgment
problems with memory or speech
puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
red, irritated eyes
redness or swelling of the breast
sensitivity to the sun
skin thinness
sore on the skin of the breast that does not heal
sores, ulcers, or white spots in the mouth or on the lips
stomach discomfort, upset, or pain
sudden loss of consciousness
sudden shortness of breath or troubled breathing
sweating
swelling
swelling of the abdominal or stomach area
thick, white vaginal discharge with no odor or with a mild odor
tightness in the chest
trouble recognizing objects
trouble thinking and planning
trouble walking
unexpected or excess milk flow from the breasts
unpleasant breath odor
unusual tiredness or weakness
unusually heavy or unexpected menstrual bleeding
vaginal bleeding or spotting
vomiting
vomiting of blood
yellow eyes or skin
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Incidence not known
Decreased interest in sexual intercourse
hives or welts
inability to have or keep an erection
increased hair growth, especially on the face
increased in sexual ability, desire, drive, or performance
increased interest in sexual intercourse
irritability
leg cramps
loss in sexual ability, desire, drive, or performance
loss of scalp hair
mental depression
mood disturbances
patchy brown or dark brown discoloration of the skin
redness of the skin
twitching, uncontrolled movements of the tongue, lips, face, arms, or legs
weight changes
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
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Pros and cons of Estradiol gel (Divigel)
Pros
- Relieves bothersome menopausal symptoms, such as hot flashes and night sweats
- Applied directly to the skin on the thighs
- Only need to use once a day
- Available in multiple strengths to customize your dose
Cons
- Raises your risk of certain cancers, blood clots, and strokes
- Risk of exposing others to estrogen through skin contact
- Might also need to take a progestin medication if you have a uterus
- Need to wait for the gel to dry completely before bathing, showering, or swimming
Pharmacist tips for Estradiol gel (Divigel)
- Estradiol gel (Divigel) can transfer to others through skin-to-skin contact with the application site. After applying the gel, let it dry completely and wear clothing over the area. And wash your hands with soap and water immediately after applying the medication. Avoid letting others contact the application area for at least 1 hour.
- If you miss a dose of estradiol gel (Divigel), and your next dose is less than 12 hours away, skip the missed dose and apply your regular dose the next day. If the missed dose is more than 12 hours away, apply the missed dose and continue with your regular schedule the following day.
- Avoid swimming, showering, and bathing for at least 1 hour after applying estradiol gel (Divigel). Washing the area too soon can reduce the amount of estrogen your body absorbs, affecting how well the medication works.
- Using sunscreen while applying estradiol gel (Divigel) might change how much estrogen your body absorbs. If you’re unsure about using sunscreen with this medication, ask your prescriber for guidance.
- If you have a uterus, your prescriber might recommend taking a progestin medication along with estradiol gel (Divigel) to lower the risk of uterine (endometrial) cancer. Check with your prescriber to confirm your treatment plan.
- Using estradiol gel (Divigel) for a long time can raise the risk of serious health problems, such as breast cancer and heart attacks. That's why it's important to use the lowest dose for the shortest possible duration. Talk with your prescriber regularly to decide if you should continue treatment.
- Estradiol gel (Divigel) is flammable, meaning it can easily catch on fire. Avoid fire, flames, or smoking until the gel has dried to protect yourself and others around you.
- Store estradiol gel (Divigel) at room temperature. Throw away used packets in the trash safely to prevent accidental contact with others.
How to use estradiol gel (Divigel):
- Make sure to read the instructions for use carefully before using the medication to make sure you apply the dose correctly.
- (1) Wash and dry your hands, then sit comfortably. (2) Open the estradiol packet and squeeze the entire contents onto your upper thigh. Spread it in a thin layer over an area that's 5 by 7 inches. You don't need to massage or rub in the gel. Wait for it to dry completely before putting on clothes. (3) Throw away the empty packet and wash your hands with soap and water to prevent transferring the gel to others.
- Alternate application between your left and right thigh each day to prevent skin irritation.
- If you spill any gel, don't open a new packet. Just skip that dose and apply your normal dose the next day.
Common questions about Divigel
Divigel usually starts to relieve menopausal symptoms, like hot flashes, within about 2 weeks. For some people, it can take months to feel the full effects. If you don’t see any improvement after a few months, talk to your prescriber.
Not likely. Some people have reported weight changes, including both weight gain and weight loss, while using Divigel. But these changes are usually caused by hormonal shifts during menopause, not the medication itself. If you’re worried about weight changes during menopause, talk to your gynecologist.
Yes. Divigel is a bioidentical hormone because it contains estradiol only. Estradiol is a man-made hormone that's chemically similar to the estrogen hormone your body makes.
Apply Divigel to clean, dry skin on the upper thighs. Use it on one thigh at a time, and alternate between thighs each day. Spread the gel in a thin layer over the area, but you don't need to rub it in. Avoid applying it to broken or irritated skin, and let the gel dry before putting on clothes. Be sure to wash your hands after application to prevent spreading the medication to others.
No. Divigel is meant to be applied only to the skin on your upper thighs, as this area allows the medication to be absorbed properly. Applying the gel to your face or other areas might cause irritation or affect how well the medication works. Always follow the instructions provided by your prescriber.
Not typically. But menopause itself can cause changes in hair, including hair loss. If you experience hair loss while using this medication, talk to your prescriber.
It can take between 1 to 2 days for most of Divigel to leave your body. This is based on the medication's half-life. But how long it stays in your system can vary depending on factors like your age and health conditions, so it can be different for each person.
Divigel and EstroGel are both medications containing estradiol gel, but they differ in packaging and application areas. Divigel comes in single-use packets applied to the upper thigh, while EstroGel is available in a pump and applied to the entire arm. Both medications are available as brand-name and generic versions.
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Risks and warnings for Estradiol gel (Divigel)
Estradiol gel (Divigel) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.
Risk of blood clot
- Risk factors: People ages 50 years and older| High blood pressure | People identified as obese | High cholesterol | Diabetes | History of smoking cigarettes | Recent surgery or bedrest
Estrogens like estradiol gel (Divigel) can raise the risk of serious blood clots. Higher estrogen levels can raise blood proteins that promote clot formation. These clots can form anywhere in the body and might be life-threatening. Get medical attention right away if you have any signs or symptoms of a blood clot:
- Brain (e.g., stroke): weakness or numbness in your arms, legs, or face on one side of the body, trouble speaking, blurry vision, dizziness, loss of balance, trouble walking, or confusion
- Eyes (e.g., retinal thrombosis): trouble seeing, bulging eye, double vision
- Heart (e.g., heart attack): chest pain, sweating, nausea, or dizziness
- Lungs (e.g., pulmonary embolism or PE): trouble breathing, chest pain, or cough
- Legs (e.g., deep vein thrombosis or DVT): cramps, swelling, pain, or muscle tightness
Your risk of blood clots is higher if you're older, smoke cigarettes, or have certain medical conditions. It's also higher if you're on bedrest after surgery. Your gynecologist might temporarily stop estradiol gel (Divigel) for 4-6 weeks before surgery. Talk with your gynecologist if you have any questions regarding your risk of blood clots.
Uterine (endometrial) cancer
- Risk factors: Estrogen therapy without additional progestin | Using estrogen therapy for more than 1 year
Estrogens like estradiol gel (Divigel) can thicken and change the lining of your uterus (endometrium). This can lead to uncontrolled growth, which might cause uterine (endometrial) cancer. To reduce this risk, it's generally recommended to take progestin, another hormone, along with estrogen. Progestin helps slow the growth of the uterine lining. Watch for warning signs of uterine cancer, such as vaginal bleeding that doesn’t stop or keeps coming back. Contact your prescriber right away if you notice any unusual vaginal bleeding.
Breast cancer
- Risk factors: Personal or family history of breast cancer | Long-term use of estrogen and progestin together
There's a higher risk of developing breast cancer when taking estrogen, such as estradiol gel (Divigel), and progestin medications together. The longer you take this combination, the higher your risk is. That's why it's best to use estradiol gel (Divigel) only for the shortest amount of time needed. Make sure to check your breasts regularly for changes and get breast scans (mammograms). Let your prescriber know if you notice any unusual changes in breast shape, size, or color.
Dementia
- Risk factors: Age 65 years or older
People using estrogen therapy like estradiol gel (Divigel) may have a higher risk of dementia, especially if treatment begins after age 65. Early symptoms of dementia include new forgetfulness, confusion, getting lost, or wandering. If you’re concerned about this risk, talk to your prescriber.
Gallbladder and liver problems
- Risk factors: History of or current liver problems
Estradiol gel (Divigel) can cause problems with your gallbladder, and some people have needed gallbladder surgery after starting this medication. If you experience stomach pain, nausea or vomiting that doesn't go away, fever, or a yellowing of the skin and eyes (jaundice), speak with your prescriber or get medical attention right away.
The estrogen in estradiol gel (Divigel) is processed by the liver. So if your liver isn't working properly, you might have more side effects from this medication. If you currently have or have had any liver problems, including issues during a past pregnancy, you shouldn't use estradiol gel (Divigel).
Changes in calcium levels in the blood
- Risk factors: Breast cancer | Cancer that has spread to the bones | Low parathyroid hormone levels
Taking estrogens like estradiol gel (Divigel) can lead to severely high calcium levels in people with breast cancer that has spread to their bones. High calcium can cause symptoms like thirst, stomach pain, nausea, vomiting, constipation, bone pain, muscle weakness, or confusion. Tell your prescriber if you have any of these symptoms because you might have to stop taking estradiol gel (Divigel).
Use estradiol gel (Divigel) carefully if you have low parathyroid hormone levels (hypoparathyroidism), which can lead to low calcium in your body. Let your prescriber know if you have signs of low calcium such as burning or tingling of your fingers, toes, or lips, muscle pain and cramps, or confusion.
Vision problems
Although very rare, some people taking estrogens have experienced vision problems caused by a blood clot in the eyes. If you have sudden partial or complete vision loss, bulging eyes, double vision, or migraines, stop taking estradiol gel (Divigel) and tell your prescriber immediately.
High triglycerides
- Risk factors: High levels of triglycerides
Estrogens can raise the amount of fats in your blood (triglycerides), which can lead to heart problems or pancreatitis, a serious inflammation of the pancreas. Your prescriber might recommend regular blood tests to watch for this while you're taking estradiol gel (Divigel). If you experience sudden stomach or back pain, nausea, vomiting, sudden weight loss, or a fast heart rate, contact your prescriber or seek medical care right away.
Low thyroid hormone levels (hypothyroidism)
- Risk factors: Low thyroid hormone levels
Estradiol gel (Divigel) can affect thyroid hormone levels in your blood. If you're taking medications for low thyroid hormone levels, you might need a higher dose of your thyroid replacement therapy. Your prescriber might recommend regular blood tests to check your thyroid hormone levels while you're taking this medication.
Fluid Retention
- Risk factors: History of heart or kidney problems
Estrogen products like estradiol gel (Divigel) can cause some fluid retention or edema, especially in people with heart conditions, like congestive heart failure, or kidney problems. If you notice unusual swelling in any part of your body or if you suddenly gain weight over a short period of time, let your care team know.
Worsening of other medical conditions
- Risk factors: History of asthma or diabetes | History of lupus | History of seizures or migraines | History endometriosis
Taking estrogen-containing medications like estradiol gel (Divigel) can worsen certain medical conditions. These include endometriosis, hereditary angioedema, asthma, diabetes, migraine, and seizures. Before you start estradiol gel (Divigel) let your healthcare team know about your past medical history so they can talk with you about the risks and benefits of taking this medication.
Potential skin-to-skin transfer
There's a chance that estradiol gel (Divigel) could transfer to someone else through skin-to-skin contact with the application site. To avoid this, make sure the gel is completely dry before allowing others to touch the area. Once the gel is dry, cover the application site with clothing.
Estradiol gel (Divigel) dosage
Carton| Dosage | Quantity | Price as low as | Price per unit |
|---|---|---|---|
| 30 packets of 0.25mg gel | 1 carton | $42.08 | $42.08 |
| 30 packets of 0.5mg gel | 1 carton | $42.08 | $42.08 |
| 30 packets of 0.75mg gel | 1 carton | $42.08 | $42.08 |
| 30 packets of 1mg gel | 1 carton | $42.08 | $42.08 |
| 30 packets of 1.25mg gel | 3 cartons | $76.65 | $25.55 |
Typical dosage for Estradiol gel (Divigel)
The typical starting dose is 0.25 grams (one packet), applied to the skin of either your right or left upper thigh once a day. If needed, your prescriber might raise your dose up to the maximum of 1.25 grams per day.
More on Estradiol gel (Divigel) dosage
Interactions between Estradiol gel (Divigel) and other drugs
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Abametapir
- Amifampridine
- Amoxicillin
- Ampicillin
- Amprenavir
- Apalutamide
- Aprepitant
- Armodafinil
- Artemether
- Bacampicillin
- Betamethasone
- Bexarotene
- Bosentan
- Brigatinib
- Bupropion
- Carbamazepine
- Carbenicillin
- Cefaclor
- Cefadroxil
- Cefdinir
- Cefditoren
- Cefixime
- Cefpodoxime
- Cefprozil
- Ceftazidime
- Ceftibuten
- Cefuroxime
- Cenobamate
- Ceritinib
- Clavulanic Acid
- Clobazam
- Cloxacillin
- Colesevelam
- Conivaptan
- Cyclacillin
- Cyclosporine
- Dabrafenib
- Darunavir
- Dexamethasone
- Dicloxacillin
- Donepezil
- Doxycycline
- Efavirenz
- Elagolix
- Elvitegravir
- Encorafenib
- Enzalutamide
- Eslicarbazepine Acetate
- Etravirine
- Fosamprenavir
- Fosaprepitant
- Fosnetupitant
- Fosphenytoin
- Griseofulvin
- Guar Gum
- Isotretinoin
- Ivosidenib
- Lesinurad
- Lixisenatide
- Lorlatinib
- Lumacaftor
- Minocycline
- Mitotane
- Modafinil
- Mycophenolate Mofetil
- Mycophenolic Acid
- Nafcillin
- Nelfinavir
- Netupitant
- Nevirapine
- Octreotide
- Oxacillin
- Oxcarbazepine
- Oxytetracycline
- Penicillin G
- Penicillin G Procaine
- Penicillin V
- Phenobarbital
- Phenylbutazone
- Phenytoin
- Pitolisant
- Pixantrone
- Prednisone
- Primidone
- Rifabutin
- Rifampin
- Rifapentine
- Ritonavir
- Rufinamide
- Secobarbital
- St John's Wort
- Sugammadex
- Sultamicillin
- Tazemetostat
- Telaprevir
- Tetracycline
- Theophylline
- Ticarcillin
- Tigecycline
- Tizanidine
- Topiramate
- Ulipristal
- Valproic Acid
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Atazanavir
- Diazepam
- Ginseng
- Lamotrigine
- Levothyroxine
- Licorice
- Lorazepam
- Prednisolone
- Selegiline
- Tacrine
- Temazepam
- Tipranavir
- Triazolam
- Troleandomycin
- Voriconazole
- Warfarin
How much does Estradiol gel (Divigel) cost?
Estradiol gel (Divigel) contraindications
Contraindications are specific health conditions or situations in which a person should not take a medication due to safety concerns. If you have any of the following conditions or if any of the following apply to you, let your healthcare provider know because Estradiol gel (Divigel) will not be safe for you to take.
- Undiagnosed abnormal vaginal bleeding
- History of breast cancer
- History of cancer that depends on estrogen for growth
- Blood clots or blood clotting conditions
- History of stroke or heart attack
- Liver problems
What are alternatives to Estradiol gel (Divigel)?
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