Estraderm (Transdermal)

Estradiol transdermal gel, patch, and spray are used to treat moderate to severe menopause symptoms (for example, feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating [hot flashes]) in women who have a uterus. It is also used to treat changes in and around the vagina (such as vaginal dryness, itching, and burning) caused by low estrogen levels or menopause. This medicine is also used to treat certain conditions in women before menopause if their ovaries do not produce enough estrogens naturally, and to prevent osteoporosis after menopause.

Estradiol is an estrogen hormone. The hormone from the patch, gel, and spray is absorbed through your skin into your body.

This medicine is available only with your doctor's prescription.

It is very important for your doctor to check your progress at regular visits to ensure this medicine is working properly and does not cause unwanted effects. These visits may be every 3 to 6 months. You may need a pelvic exam, breast exam, and mammogram (breast x-ray) to check for unwanted effects, unless your doctor tells you otherwise. Make sure to keep all appointments.

It is unlikely that a postmenopausal woman may become pregnant. However, you should know that using this medicine while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using this medicine may increase your risk of blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even higher if you have high blood pressure, high cholesterol in your blood, diabetes, are overweight, or smoke cigarettes. Contact your doctor immediately if you experience confusion, difficulty speaking, double vision, headaches, an inability to move your arms, legs, or facial muscles, or if you cannot speak.

Using this medicine for a long time may increase your risk of breast cancer, endometrial cancer, or uterine cancer. Do not use this medicine if you have had your uterus (womb) removed (hysterectomy). Check with your doctor immediately if you experience abnormal vaginal bleeding.

Using this medicine may increase your risk of dementia, especially in women 65 years of age and older.

Using this medicine may increase your risk of gallbladder disease. Talk with your doctor about this risk.

Tell your medical doctor or dentist that you are using this medicine before any kind of surgery (including dental surgery) or emergency treatment. Your doctor will decide if you should continue using this medicine. This medicine may also affect the results of certain medical tests.

Check with your doctor immediately if you have a severe headache, sudden loss of vision, or any other change in vision while using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may cause a serious allergic reaction, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while using this medicine.

Check with your child's doctor right away if your child begins to have nipple or breast swelling or tenderness in females, or enlargement of the breasts in males. Your child may have been exposed to this medicine.

Do not let your pets lick or touch the arm where this medicine was applied. Small pets may be sensitive to this medicine. Call your pet's veterinarian if your pet starts to have nipple or breast enlargement, swelling of the vulva, or any signs of illness.

Do not take other medicines or drink grapefruit juice unless you discuss it with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

In deciding to use a medicine, you and your doctor will weigh the risks of taking the medicine against its benefits. Here are some important points to consider:

Allergies

Inform your doctor if you have ever had any unusual or allergic reactions to this medicine or any other medicines. Also, let your healthcare professional know if you have any other allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

The use of estradiol transdermal patch, gel, and spray is not recommended for children. Safety and effectiveness have not been proven.

Geriatric

While studies on how age affects the use of estradiol transdermal patch, gel, and spray have not been done in older adults, no specific problems for this age group have been reported so far. However, older patients may have a higher risk of breast cancer, stroke, or dementia, which may require caution when using estradiol transdermal patch, gel, and spray.

Breast Feeding

There are no adequate studies to determine the risk to infants when this medication is used during breastfeeding. Weigh the potential benefits against the possible risks before using this medication while breastfeeding.

Interactions with Medicines

Some medicines should never be used together, while others can be used together even if an interaction might happen. In these cases, your doctor may change the dose or take other precautions. It is very important that your healthcare professional knows if you are taking any of the medicines listed below. The following interactions are based on their potential significance and are not a complete list.

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.

• Tranexamic Acid

Using this medicine with any of the following medicines is usually not recommended, but may be necessary 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
• Belzutifan
• Betamethasone
• Bexarotene
• Bosentan
• Bupropion
• Carbamazepine
• Carbenicillin
• Cefaclor
• Cefadroxil
• Cefdinir
• Cefditoren
• Cefixime
• Cefpodoxime
• Cefprozil
• Ceftazidime
• Ceftibuten
• Cefuroxime
• Cenobamate
• Ceritinib
• Clobazam
• Cloxacillin
• Colesevelam
• Conivaptan
• Cyclacillin
• Cyclosporine
• Dabrafenib
• Darunavir
• Dexamethasone
• Dicloxacillin
• Donepezil
• Doxycycline
• Efavirenz
• Elagolix
• Elvitegravir
• Encorafenib
• Enzalutamide
• Eslicarbazepine Acetate
• Etravirine
• Fedratinib
• Fexinidazole
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Griseofulvin
• Guar Gum
• Isotretinoin
• Itraconazole
• Ivosidenib
• Lesinurad
• Lixisenatide
• Lorlatinib
• Lumacaftor
• Mavacamten
• Meropenem
• Minocycline
• Mitapivat
• Mitotane
• Mobocertinib
• 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
• Prednisolone
• Prednisone
• Primidone
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Rufinamide
• Secobarbital
• Somatrogon-ghla
• St John's Wort
• Sugammadex
• Sultamicillin
• Tazemetostat
• Telaprevir
• Tetracycline
• Theophylline
• Ticarcillin
• Tigecycline
• Tirzepatide
• Tizanidine
• Topiramate
• Ulipristal
• Valproic Acid

Using this medicine with any of the following medicines may increase the risk of certain side effects, but using both may be necessary for your treatment. If both medicines are prescribed together, your doctor may adjust the dose or how often you use one or both of the medicines.

• Atazanavir
• Diazepam
• Ginseng
• Lamotrigine
• Levothyroxine
• Licorice
• Lorazepam
• Selegiline
• Tacrine
• Temazepam
• Tipranavir
• Triazolam
• Troleandomycin
• Voriconazole
• Warfarin

Interactions with Food/Tobacco/Alcohol

Some medicines should not be taken at or around mealtime or with certain types of food due to potential interactions. Using alcohol or tobacco with certain medicines may also cause interactions. The following interactions are based on their significance and are not a complete list.

Using this medicine with any of the following may increase the risk of certain side effects but may be unavoidable in some situations. If used together, your doctor may adjust the dose or provide special instructions regarding food, alcohol, or tobacco use.

• Caffeine

Other Medical Problems

Other medical conditions may affect the use of this medicine. Be sure to inform your doctor if you have any other medical problems, especially:

• Abnormal or unusual vaginal bleeding or
• Blood clots (e.g., deep vein thrombosis, pulmonary embolism), either active or in history or
• Breast cancer, known or suspected, or history of or
• Dementia or
• Heart attack, either active or recent (within the past 12 months) or
• Heart or blood vessel disease or
• Liver disease or
• Protein C, protein S deficiency, or antithrombin deficiency, or other known blood clotting disorders or
• Stroke, either active or recent (within the past 12 months) or
• Surgery with a long period of inactivity or
• Tumors (estrogen-dependent), known or suspected—This medicine should not be used in patients with these conditions.

• Asthma or
• Cancer, history of or
• Diabetes or
• Edema (fluid retention or body swelling) or
• Endometriosis or
• Epilepsy (seizures) or
• Gallbladder disease or
• Hereditary angioedema (swelling of the face, lips, tongue, or throat) or
• Hypercalcemia (high calcium in the blood) or
• Hypertension (high blood pressure) or
• Hypertriglyceridemia (high triglycerides or fats in the blood) or
• Hypocalcemia (low calcium in the blood), severe or
• Hypothyroidism (an underactive thyroid) or
• Jaundice during pregnancy or from past hormonal therapy or
• Kidney disease or
• Liver tumors or
• Migraine headache or
• Obesity or
• Porphyria (an enzyme problem) or
• Systemic lupus erythematosus (SLE)—Use with caution. This may worsen these conditions.

Along with its necessary effects, a medicine can cause some unwanted effects. While not all of these side effects may happen, if they do, you might need medical attention.

Check with your doctor right away if any of the following side effects occur:

Incidence not known

• Acid or sour stomach
• anxiety
• backache
• belching
• blistering, peeling, or loosening of the skin
• bloating
• blurred vision
• breast tenderness, enlargement, pain, or discharge
• change in vaginal discharge
• changes in skin color
• changes in vision
• chest pain, discomfort, or tightness
• chills
• clay-colored stools
• clear or bloody discharge from the nipple
• confusion
• constipation
• cough
• darkening of the urine
• diarrhea
• difficulty with swallowing
• dimpling of the breast skin
• dizziness or lightheadedness
• double vision
• fainting
• fast heartbeat
• fever
• fluid-filled skin blisters
• full or bloated feeling or pressure in the stomach
• headache
• headache, severe and throbbing
• heartburn
• hives, itching, skin rash
• 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
• nausea
• 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
• seizures
• sensitivity to the sun
• skin thinness
• sore on the skin of the breast that does not heal
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach cramps, discomfort, upset, pain, or swelling
• sudden loss of consciousness
• sudden trouble breathing
• sweating
• thick, white vaginal discharge with no odor or with a mild odor
• tremor
• 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 happen that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your healthcare professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your healthcare professional if any of the following side effects continue or are bothersome, or if you have any questions about them:

Less common

• Back pain
• difficulty with moving
• muscle aches, pain, or stiffness
• stuffy or runny nose

Incidence not known

• Decreased interest in sexual intercourse
• heavy bleeding
• increased hair growth, especially on the face
• increased 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 happen 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.

In the U.S.

• Alora
• Climara
• Divigel
• Elestrin
• Esclim
• Estraderm
• Estrasorb
• EstroGel
• Evamist
• Menostar
• Minivelle
• Vivelle
• Vivelle-Dot

In Canada

• Estradot Transdermal
• Estradot Transdermal Therapeutic System
• Estradot Transdermal Therapeutic System
• Oesclim
• Rhoxal-Estradiol Derm 50
• Rhoxal-Estradiol Derm 75
• Roxal-Estradiol Derm 100
• Vivelle 100 Mcg
• Vivelle 25 Mcg
• Vivelle 37.5 Mcg

Available Dosage Forms:

• Patch, Extended Release
• Gel/Jelly
• Spray

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Estrogen

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

This medicine is for use on the skin only. Do not get it in your eyes, nose, mouth, breast, or vagina. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

This medicine comes with a patient information insert and patients instructions. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.

Wash your hands with soap and water before and after using this medicine.

To use the patch:

• Wash your hands with soap and water before and after you use this medicine.
• Carefully tear open the pouch when you are ready to put the patch on your skin. Do not cut it.
• Peel off the backing from the patch and apply the patch to a clean, dry, and hair-free area of the lower stomach or upper buttock area. This area must be free of powder, oil, or lotion for the patch to stick on to your skin.
• Press the patch firmly in place with your hand for about 10 seconds.
• Do not apply the patch on the breast or over any skin folds. Do not apply the patch on oily, broken, burned, or irritated skin, or areas with skin conditions (eg, birth marks, tattoos). Avoid applying the patch on the waistline or other places where tight clothing may rub it off.
• Wear the patch at all times until it is time to put on a new patch. Do not expose it to the sun for long periods of time.
• When replacing your patch, make sure to apply the new patch to a different area of your lower abdomen. Wait at least 1 week before applying a patch to the same area.
• When changing a patch, slowly peel it off from your skin. If you have any patch adhesive left on your skin, allow it to dry for 15 minutes and gently rub the sticky area with oil or lotion to remove it. It is best to change your patch on the same days of each week to help you remember.
• You may take a bath, shower, or swim while using this medicine. Doing so will not affect the patch.
• If a patch falls off, just put it back on a different area. If the patch does not stick completely, put on a new patch but continue to follow your original schedule for changing your patch.
• To throw away a used patch: Fold the patch in half with the sticky side together and place it in a sturdy child-proof container. Throw this container in the trash away from children and pets. Do not flush the patch down the toilet.

To use the spray:

• The spray form of this medicine comes in an applicator that delivers a measured amount of estradiol to the skin with each spray. When using a new spray applicator, prime the pump by holding the spray upright and pumping 3 times. Priming is only necessary the first time you use a new spray applicator. Do not prime again.
• Apply the medicine to clean, dry, and unbroken skin on the inside of the forearm between the elbow and the wrist. Do not apply to open wounds, cuts, abrasions, or rashes. Do not apply the medicine directly to your breasts or in or around the vagina.
• Allow the medicine to dry for at least 2 minutes before dressing, and at least 1 hour before washing.
• If your doctor tells you to increase your dose, move the applicator to an area of the skin next to your previous application site, before applying the second or third spray.
• Do not massage or rub Evamist® spray into your skin.
• Do not allow your child to touch the area of the arm where the medicine was sprayed. If you cannot avoid being close with your child, wear clothes with long sleeves to cover the application site.
• If your child comes in direct contact with the arm where the medicine was sprayed, wash your child's skin right away with soap and water.
• Do not allow your pets to lick or touch the arm where the medicine was sprayed.
• Always place the protective cover back on the applicator of the spray.
• Do not use the applicator for more than 56 sprays even though the bottle may not be fully empty. You may not get the correct dose.
• Apply sunscreen at least 1 hour before applying Evamist®.

To use the gel:

• The gel form of this medicine comes in a pump. Each time you press the pump you will get the same amount of medication. You may need to prime the pump by pumping 5 times (EstroGel®) or 10 times (Elestrin™) the first time you use it. Follow the patient instructions for the container you use. After you prime the pump, do not press the pump more than 1 time each time you use it.
• Apply the gel to clean, dry, and unbroken skin. Apply EstroGel® after your bath or shower. If you go swimming. try to leave as much time as possible between using EstroGel® and going swimming. Spread the gel as thinly as possible over the entire area on the inside and outside of your upper arm from your wrist to your shoulder area. Do not apply the medicine directly to your breasts or in or around your vagina. Do not massage or rub in EstroGel®.
• Do not allow others to come in contact with the area of skin where you applied the gel for at least 1 hour after you use the medicine. Do not allow others to apply the gel for you. Allow the medicine to dry for at least 5 minutes before you get dressed.
• Do not use EstroGel® for more than 30 doses even the canister may not be fully empty. You may not get the correct dose.
• Apply sunscreen at least 25 minutes after using the gel. Avoid applying sunscreen on the same application site for 7 days or more.

The gel and spray contain alcohol and are flammable. Avoid using it near an open flame or while smoking.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For hot flashes and other symptoms caused by menopause: For transdermal dosage form (gel): Adults— Elestrin™: Apply one dose (0.87 grams) of the gel to the upper arm once a day. Your doctor may adjust your dose as needed. EstroGel®: Apply one dose (1.25 grams) of the gel to the arm once a day. Your doctor may adjust your dose as needed. Children—Use is not recommended. For transdermal dosage form (patch): Adults— Climara®: At first, apply one patch (0.025 milligrams (mg)) to the lower stomach or upper buttocks area once a week. Your doctor may adjust your dose as needed. Minivelle® and Vivelle-Dot®: At first, apply one patch (0.0375 milligrams (mg)) to the lower stomach or upper buttocks area 2 times a week (every 3 to 4 days). Your doctor may adjust your dose as needed. Children—Use is not recommended. For transdermal dosage form (spray): Adults—At first, one spray once a day, usually in the morning. Your doctor may adjust your dose as needed. Children—Use is not recommended.
• For prevention of osteoporosis after menopause:For transdermal dosage form (patch): Adults— Climara®: At first, apply one patch (0.025 milligrams (mg)) to the lower stomach or upper buttock area once a week. Your doctor may adjust your dose as needed. Minivelle® and Vivelle-Dot®: At first, apply one patch (0.025 milligrams (mg)) to the lower stomach or upper buttock area 2 times a week (every 3 to 4 days). Your doctor may adjust your dose as needed. Children—Use is not recommended.
• For the treatment of low estrogen levels:For transdermal dosage form (patch): Adults—At first, apply one patch (0.025 milligrams (mg)) to the lower stomach or upper buttock area once a week. Your doctor may adjust your dose as needed. Children—Use is not recommended.

Missed Dose

If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Do not use Evamist® spray if it has been more than 12 hours since you missed your last dose.

Storage

Store the patches at room temperature in a closed container, away from heat, moisture, and direct light.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.