ISSUE: FDA notified healthcare professionals and patients that it is reviewing reports of adverse effects from estradiol transdermal spray (Evamist), an estrogen hormone used to reduce hot flashes during menopause. Children unintentionally exposed to the drug through skin contact with women may experience premature puberty. Female children may experience nipple swelling and breast development. Male children may experience breast enlargement.
BACKGROUND: Estradiol transdermal spray is a topical product, sprayed on the skin on the inside of the forearm between the elbow and the wrist. FDA is currently reviewing reported adverse events and is working with the company to identify any factors that may contribute to unintended exposure. The Agency will update the public when this review is complete. FDA and the company are also evaluating ways to minimize the risk.
RECOMMENDATION: Patients should make sure that children are not exposed to estradiol transdermal spray and that children do not come into contact with any skin area where the drug was applied. Women who cannot avoid contact with children should wear a garment with long sleeves to cover the application site. For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Estradiol increases the risk that you will develop endometrial cancer (cancer of the lining of the uterus [womb]). The longer you use estradiol, the greater the risk that you will develop endometrial cancer. If you have not had a hysterectomy (surgery to remove the uterus), you should be given another medication called a progestin to take with topical estradiol. This may decrease your risk of developing endometrial cancer but may increase your risk of developing certain other health problems, including breast cancer. Before you begin using topical estradiol, tell your doctor if you have or have ever had cancer and if you have abnormal or unusual vaginal bleeding. Call your doctor immediately if you have abnormal or unusual vaginal bleeding during your treatment with topical estradiol. Your doctor will watch you closely to help ensure you do not develop endometrial cancer during or after your treatment.
In a large study, women who took estrogens (a group of medications that includes estradiol) by mouth with progestins had a higher risk of heart attacks, strokes, blood clots in the lungs or legs, breast cancer, and dementia (loss of ability to think, learn, and understand). Women who use topical estradiol alone or with progestins may also have a higher risk of developing these conditions. Tell your doctor if you smoke or use tobacco, if you have had a heart attack or a stroke in the past year and if you or anyone in your family has or has ever had blood clots or breast cancer. Also tell your doctor if you have or have ever had high blood pressure, high blood levels of cholesterol or fats, diabetes, heart disease, lupus (a condition in which the body attacks its own tissues causing damage and swelling), breast lumps, or an abnormal mammogram (x-ray of the breast used to find breast cancer).
The following symptoms can be signs of the serious health conditions listed above. Call your doctor immediately if you experience any of the following symptoms while you are using topical estradiol: sudden, severe headache; sudden, severe vomiting; speech problems; dizziness or faintness; sudden complete or partial loss of vision;double vision; weakness or numbness of an arm or a leg; crushing chest pain or chest heaviness; coughing up blood; sudden shortness of breath; breast lumps or other breast changes; discharge from nipples; difficulty thinking clearly, remembering, or learning new things; or pain, tenderness, or redness in one leg.
You can take steps to decrease the risk that you will develop a serious health problem while you are using topical estradiol. Do not use topical estradiol alone or with a progestin to prevent heart disease, heart attacks, or strokes. Use the lowest dose of topical estradiol that controls your symptoms and only use topical estradiol as long as needed. Talk to your doctor every 3-6 months to decide if you should use a lower dose of topical estradiol or should stop using the medication.
You should examine your breasts every month and have a mammogram and a breast exam performed by a doctor every year to help detect breast cancer as early as possible. Your doctor will tell you how to properly examine your breasts and whether you should have these exams more often than once a year because of your personal or family medical history.
Tell your doctor if you are having surgery or will be on bedrest. Your doctor may tell you to stop using topical estradiol 4-6 weeks before the surgery or bedrest to decrease the risk that you will develop blood clots.
Talk to your doctor regularly about the risks and benefits of using topical estradiol.
Estradiol topical gel and emulsion (lotion type mixture) are used to treat and prevent hot flushes (hot flashes; sudden strong feelings of heat and sweating) in women who are experiencing menopause (change of life; the end of monthly menstrual periods). Estradiol topical gel is also used to treat vaginal dryness, itching, and burning in women who are experiencing menopause. However, women whose only bothersome symptoms are vaginal burning, itching, and dryness may benefit more from a medication that is applied topically to the vagina. Estradiol is in a class of medications called estrogen hormones. It works by replacing estrogen that is normally produced by the body.
Topical estradiol comes as a gel, a spray, and an emulsion to apply to the skin. It is usually applied once a day. Estradiol emulsion should be applied in the morning. Estradiol gel may be applied at any time of day, but should be applied at around the same time of day every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use topical estradiol exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
If you are using estradiol gel, you should apply it in a thin layer to one arm, from the wrist to the shoulder. If you are using estradiol emulsion, you should apply it to both thighs and calves (lower legs). Do not apply estradiol gel or emulsion to your breasts. Be sure that the skin where you will apply topical estradiol is clean and completely dry, and is not red, irritated, or broken.
If you take a bath or a shower or use a sauna, apply topical estradiol after you have finished bathing, showering or using the sauna and have dried your skin completely. If you plan to swim, allow as much time as possible between applying estradiol gel and swimming. Do not apply sunscreen shortly before, at the same time, or soon after you apply topical estradiol.
Estradiol gel may catch fire. When you apply estradiol gel, do not smoke or go near a fire or open flame until the gel dries.
Be careful not to get estradiol gel in your eyes. If you do get estradiol gel in your eyes, wash them with plenty of warm water right away. Call a doctor if your eyes become irritated.
You should apply estradiol gel yourself. Do not let anyone else rub the gel onto your skin.
Before you use your first dose of estradiol gel, remove the large cover of the pump and fully press down the pump twice. Wash the gel that comes out down the sink or throw it away in a trash can that is out of the reach of children and pets. This primes the pump so that it will dispense the same amount of medication each time it is pressed. Do not repeat this step after the first time you use the pump.
Hold the pump with one hand and cup your other hand below the nozzle of the pump. Press the pump firmly and fully to dispense one dose of gel onto your palm.
Use your hand to spread the gel as thinly as possible over your entire arm. Try to cover the inside and outside of your arm from your wrist to your shoulder with the gel.
Do not rub or massage the gel into your skin. Wait 5 minutes to allow the skin to dry before covering your arm with clothing.
Cover the pump with the small and large protective caps.
Wash your hands with soap and water.
Get two pouches of estradiol emulsion and sit in a comfortable position.
Open one pouch of estradiol emulsion by cutting or tearing across the notches near the top of the pouch.
Place the pouch flat on top of your left thigh with the open end facing your knee.
Hold the closed end of the pouch with one hand and use the forefinger of your other hand to push all of the emulsion in the pouch onto your thigh.
Use one or both hands to rub the emulsion into your entire thigh and calf for 3 minutes until completely absorbed.
Rub any emulsion that is left on your hands onto your buttocks.
Repeat steps 1-6 using a fresh pouch of estradiol emulsion and your right thigh so that you apply the contents of the second pouch to your right thigh and calf.
Wait until the skin where you applied estradiol emulsion is completely dry and cover it with clothing.
Wash your hands with soap and water.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medicine.
If you forget to apply a dose of estradiol gel but remember more than 12 hours before you are scheduled to apply your next dose, apply the missed dose right away. If you remember less than 12 hours before you are scheduled to apply your next dose, skip the missed dose and continue your regular dosing schedule the next day. Do not apply extra gel to make up for a missed dose.
If you forget to apply estradiol emulsion in the morning, apply it as soon as you remember. Do not apply extra emulsion to make up for a missed dose and do not apply estradiol emulsion more than once each day.
headache
breast pain or tenderness
nausea
diarrhea
constipation
gas
heartburn
weight gain or loss
mood changes
depression
nervousness
sleepiness
difficulty falling asleep or staying asleep
changes in sexual desire
back pain
runny nose
cough
flu-like symptoms
hair loss
unwanted hair growth
darkening of the skin on the face
difficulty wearing contact lenses
irritation or redness of the skin where you applied topical estradiol
swelling, redness, burning, irritation, or itching of the vagina
vaginal discharge
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
Topical estradiol may increase your risk of developing cancer of the ovaries and gallbladder disease that may need to be treated with surgery. Talk to your doctor about the risks of using this medication.
Topical estradiol may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/Safety/MedWatch] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze topical estradiol. Keep estradiol gel away from open flame. Throw away any medication that is outdated or no longer needed. Throw away your estradiol gel pump after you have used 64 doses even if it is not completely empty. Talk to your pharmacist about the proper disposal of your medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
nausea
vomiting
vaginal bleeding
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to topical estradiol.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are using topical estradiol.
Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Last Revised - 10/01/2010
AHFS® Consumer Medication Information. © Copyright, 2012. The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.