Estradiol Transdermal

Climara
(Kli-mar-uh)
(estradiol) Transdermal System

Read this Patient Information before you start using Climara and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

What is the most important information I should know about Climara (an estrogen hormone)?

• Using estrogen-alone may increase your chance of getting cancer of the uterus (womb). Report any unusual vaginal bleeding right away while you are using Climara. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes, or dementia (decline in brain function).
• Using estrogen-alone may increase your chances of getting strokes or blood clots.
• Using estrogen-alone may increase your chance of getting dementia, based on a study of women age 65 years of age or older.
• Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes or dementia.
• Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots.
• Using estrogens with progestins may increase your chance of getting dementia, based on a study of women age 65 years of age or older.
• You and your healthcare provider should talk regularly about whether you still need treatment with Climara.

What is Climara?

Climara is a prescription medicine patch (Transdermal System) that contains estradiol (an estrogen hormone).

What is Climara used for?

The Climara is used after menopause to:

• Reduce moderate to severe hot flashes
  Estrogens are hormones made by a woman's ovaries. The ovaries normally stop making estrogens when a woman is between 45 and 55 years old. This drop in body estrogen levels causes the “change of life” or menopause (the end of monthly menstrual periods). Sometimes, both ovaries are removed during an operation before natural menopause takes place. The sudden drop in estrogen levels causes “surgical menopause.”
  When the estrogen levels begin dropping, some women get very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating (“hot flashes” or “hot flushes”). In some women, the symptoms are mild, and they will not need to use estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with Climara.
• Treat moderate to severe menopausal changes in and around the vagina
  You and your healthcare provider should talk regularly about whether you still need treatment with Climara to control these problems. If you use Climara only to treat your menopausal changes in and around your vagina, talk with your healthcare provider about whether a topical vaginal product would be better for you.
• Treat certain conditions in women before menopause if their ovaries do not produce enough estrogens naturally
• Help reduce your chances of getting osteoporosis (thin weak bones)
  If you use Climara only to prevent osteoporosis due to menopause, talk with your healthcare provider about whether a different treatment or medicine without estrogens might be better for you. You and your healthcare provider should talk regularly about whether you still need treatment with Climara.

Who should not use Climara?

Do not start using Climara if you:

• have unusual vaginal bleeding
  Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• currently have or have had certain cancers
  Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus. If you have or have had cancer, talk with your healthcare provider about whether you should use Climara.
• had a stroke or heart attack
• currently have or have had blood clots
• currently have or have had liver problems
• have been diagnosed with a bleeding disorder
• are allergic to Climara or any of its ingredients
  See the list of ingredients in Climara at the end of this leaflet.
• think you may be pregnant
  Climara is not for pregnant women. If you think you may be pregnant, you should have a pregnancy test and know the results. Do not use Climara if the test is positive and talk to your healthcare provider.

What should I tell my healthcare provider before I use Climara?

Before you use Climara, tell your healthcare provider if you:

• have any unusual vaginal bleeding
  Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• have any other medical conditions
  Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, angioedema (swelling of face and tongue), or problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
• are going to have surgery or will be on bed rest.
  Your healthcare provider will let you know if you need to stop using Climara.
• are breastfeeding
  The hormone in Climara can pass into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how Climara works. Climara may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get new medicine.

How should I use Climara? For detailed instructions, see the step-by-step instructions for using Climara at the end of this Patient Information.

• Use Climara exactly as your healthcare provider tells you to use it.
• Climara is for skin use only.
• Change your Climara patch 1 time each week or every 7 days.
• Apply your Climara patch to a clean, dry area on your lower abdomen or buttocks. This area must be clean, dry, and free of powder, oil or lotion for your patch to stick to your skin.
• Apply your Climara patch to a different area of your abdomen or your buttocks each time. Do not use the same application site 2 times in the same week.
• Do not apply Climara to your breasts.
• If you forget to apply a new Climara patch, you should apply a new patch as soon as possible.
• You and your healthcare provider should talk regularly (every 3 to 6 months) about the dose you are using and whether you still need treatment with Climara.

How to Change Climara

• When changing Climara, peel off the used patch slowly from the skin.
• After removal of Climara, people usually have either no adhesive residue or light adhesive residue. If any adhesive residue remains on your skin after removing the patch, allow the area to dry for 15 minutes. Then, gently rub the area with an oil-based cream or lotion to remove the adhesive from your skin.
• Keep in mind, the new patch must be applied to a different skin area of your abdomen or buttocks. This area must be clean, dry, and free of powder, oil or lotion. The same site should not be used again for at least 1 week after removal of the patch.

What are the possible side effects of Climara?

Side effects are grouped by how serious they are and how often they happen when you are treated.

Serious, but less common side effects include:

• heart attack
• stroke
• blood clots
• dementia
• breast cancer
• cancer of the lining of the uterus (womb)
• cancer of the ovary
• high blood pressure
• high blood sugar
• gallbladder disease
• liver problems
• changes in your thyroid hormone levels
• enlargement of benign tumors of the uterus (“fibroids”)

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• new breast lumps
• unusual vaginal bleeding
• changes in vision or speech
• sudden new severe headaches
• severe pains in your chest or legs with or without shortness of breath, weakness and fatigue

Less serious, but common side effects include:

• headache
• breast tenderness or pain
• irregular vaginal bleeding or spotting
• stomach or abdominal cramps, bloating
• nausea and vomiting
• hair loss
• fluid retention
• vaginal yeast infection
• redness or irritation at the patch placement site

These are not all the possible side effects of Climara. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or does not go away.

Call your doctor for medical advice about side effects. You may report side effects to Bayer Healthcare Pharmaceuticals at 1-888-842-2937 or to FDA at 1-800-FDA-1088.

What can I do to lower my chances of a serious side effect with Climara?

• Talk with your healthcare provider regularly about whether you should continue using Climara.
• If you have a uterus, talk with your healthcare provider about whether the addition of a progestin is right for you.
• The addition of a progestin is generally recommended for women with a uterus to reduce the chance of getting cancer of the uterus (womb).
• See your healthcare provider right away if you get vaginal bleeding while using Climara.
• Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else.
• If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease.
• Ask your healthcare provider for ways to lower your chances of getting heart disease.

How should I store and throw away used Climara?

• Store Climara at room temperature 68°F to 77°F (20°C to 25°C).
• Do not store Climara patches outside of their pouches. Apply immediately upon removal from the protective pouch.
• Used patches still contain estrogen. To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Used patches should not be flushed in the toilet.

Keep Climara and all medicines out of the reach of children.

General information about the safe and effective use of Climara.

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Climara for conditions for which it was not prescribed. Do not give the Climara patch to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Climara. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Climara that is written for health professionals.

For more information, go to www.climara.com or call Bayer HealthCare Pharmaceuticals Inc at 1-888-842-2937.

What are the ingredients in Climara?

Active ingredient: estradiol

Inactive ingredient: acrylate copolymer adhesive, fatty acid esters, and polyethylene backing.

Instructions for Use

Climara
(Kli-mar-uh)
(estradiol transdermal system)

Read this Patient Information before you start using Climara and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your menopausal symptoms or your treatment.

You will need the following supplies: See Figure A

Figure A

Step 1: Pick the days you will change your Climara.

You will need to change your patch 1 time each week or every 7 days.

Step 2. Remove the Climara patch from the pouch.

• Remove patch from its protective pouch by tearing at the notch (do not use scissors). See Figure B
• Do not remove your patch from the protective pouch until you are ready to apply it.

Figure B

Step 3. Remove the adhesive liner. See Figure C

• You will see that Climara is an oval shaped clear patch that is attached to a thick, hard-plastic adhesive liner and covered by a clear, plastic film. See Figure C
• To apply your patch you must first remove the protective, clear plastic film that is attached to the clear thicker plastic backing. See Figure D
• There is a silver foil-sticker attached to the inside of the pouch. Do not remove the silver foil sticker from the pouch. See Figure E

Figure C, Figure D and Figure E

Step 4. Placing the patch on your skin.

• Apply the sticky side of the patch to 1 of the areas of skin shown below. See Figure F and Figure G
• Avoid touching the sticky side of the patch with your fingers.

Figure F and Figure G

Note:

• Avoid the waistline, since clothing and belts may cause the patch to be rubbed off.
• Do not apply Climara to your breasts.
• Only apply Climara to skin that is clean, dry, and free of any powder, oil, or lotion.
• You should not apply the patch to injured, burned, or irritated skin, or areas with skin conditions (such as birth marks, tattoos, or that is very hairy).

Step 5. Press the patch firmly onto your skin.

• Press the patch firmly in place with your fingers for at least 10 seconds
• Rub the edges of the patch to make sure that it will stick to your skin. (See Figure H)

Figugre H

Note:

• Contact with water while you are swimming, using a sauna, bathing, or showering may cause the patch to fall off.
• If your patch falls off reapply it. If you cannot reapply the patch, apply a new patch to another area (See Figures F and G), and continue to follow your original application schedule.
• If you stop using your Climara patch or forget to apply a new patch as scheduled, you may have spotting, or bleeding, and your symptoms may come back.

Step 6: Throwing away your used patch.

• When it is time to change your patch, remove the old patch before you apply a new patch.
• To throw away the patch, fold the sticky side of the patch together, place it in a sturdy child-proof container, and place this container in the trash. Used patches should not be flushed in the toilet.

The Esclim™ estradiol transdermal system contains estradiol in a polymeric adhesive. The system is designed to release 17Ò²estradiol continuously upon application to intact skin.

Five systems are available to provide nominal in vivo delivery of 0.025, 0.0375, 0.05, 0.075, or 0.1 mg of estradiol per day via skin of average permeability. Each corresponding system having an active surface area of 11, 16.5, 22, 33, or 44 cm2 contains 5, 7.5, 10, 15, or 20 mg of estradiol USP, respectively.

The composition of the systems per unit area is identical.

Estradiol USP (17Ò²estradiol) is a white, crystalline powder, chemically described as estra-1, 3, 5 (10)triene3, 17Ò²diol. The structural formula is:

The molecular formula of estradiol is C18 H24 O2. The molecular weight is 272.39.

Esclim (estradiol transdermal) transdermal systems are composed of a soft, flexible, rectangular foam backing material with rounded corners, covered on 1 side with a self-adhesive polymer matrix which contains estradiol and pharmacologically inactive components. The adhesive surface is covered by a transparent protective release liner as shown in the diagram below.

The active component of the system is estradiol. The remaining components of the system (EVA copolymers, ethylcellulose, octyldodecanol, dipropylene glycol, polyester protective release liner) are pharmacologically inactive.

See WARNINGS and Boxed Warning regarding the potential adverse effects on the fetus, the induction of malignant neoplasms, gallbladder disease, cardiovascular disease, elevated blood pressure, and hypercalcemia.

Skin irritation: In controlled clinical studies with Esclim (estradiol transdermal) , the most commonly reported adverse events were topical reactions of erythema and/or pruritus at the application site. In general these reactions caused patients little or no discomfort, and led to premature discontinuation of treatment in 0.9% (3/317) of patients in these trials. The rate of application site reactions, based on 8,135 applications of the 0.025, 0.05, and 0.1 Esclim (estradiol transdermal) systems in these trials was 6.1 per 100 applications (4.9, 5.4, 10.7 for the 3 Esclim (estradiol transdermal) doses respectively) compared to 6.2 in the placebo treated patients (2,014 applications).

In a placebo-controlled trial of Esclim (estradiol transdermal) 0.025, 0.05, and 0.1 conducted in 196 patients in the US, the adverse events reported by at least 5% of patients in 1 or more of the treatment groups are shown in Table 5.

Urogenital Adverse Events (See Precautions: Addition of a progestin): In the US placebo-controlled study, 72 patients were included who had intact uteri. As expected, after 12-13 weeks of continuous unopposed therapy, findings of endometrial hyperplasia (diagnosed either by endometrial biopsy and/or ultrasonography) were increased with increasing doses of estradiol (placebo: 0/18 patients; Esclim (estradiol transdermal) 0.025: 1/14 (7.1%); Esclim (estradiol transdermal) 0.05: 12/22 (54.5%); Esclim (estradiol transdermal) 0.1: 10/18 (55.6%). In the 86 patients who had not previously undergone a total hysterectomy, vaginal bleeding was also increased with increasing doses of estradiol [placebo: 2/21 patients (9.5%); Esclim (estradiol transdermal) 0.025: 6/19 (31.6%); Esclim (estradiol transdermal) 0.05: 14/25 (56.0%); Esclim (estradiol transdermal) 0.1: 12/21 (57.1%)].

In 2 long-term studies involving a total of 488 patients treated for a mean duration of 618 days and up to 3.5 years, the nature and incidence of adverse events did not change with prolonged duration of treatment.

The following additional adverse reactions have been reported with estrogen therapy:

1. Genitourinary System. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting; increase in size of uterine leiomyomata; vaginal candidiasis; change in amount of cervical secretion.

2. Breasts. Tenderness, enlargement.

3. Gastrointestinal. Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; gallbladder disease.

4. Skin. Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism.

5. Eyes. Steepening of corneal curvature: intolerance to contact lenses.

6. Central Nervous System. Headache, migraine, dizziness; mental depression; chorea.

7. Miscellaneous. Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; changes in libido.

Estraderm® (estradiol transdermal system) is indicated in:

• Treatment of moderate to severe vasomotor symptoms associated with the menopause.
• Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
• Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
• Prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risks of osteoporosis and non-estrogen medications should be carefully considered.

The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 IU/day may also be required to ensure adequate daily intake in postmenopausal women.

Estradiol is a form of estrogen, a female sex hormone that regulates many processes in the body.

Estradiol transdermal skin patches are used to treat certain symptoms of menopause such as hot flashes, and vaginal dryness, burning, and irritation. This medication is also used to prevent postmenopausal osteoporosis, or to treat ovarian disorders.

Estradiol transdermal may also be used for purposes not listed in this medication guide.

Grapefruit and grapefruit juice may interact with estradiol and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

Estradiol can harm an unborn baby or cause birth defects. Do not use if you are pregnant.

You should not use this medication if you have any of the following conditions: liver disease, a bleeding disorder, unusual vaginal bleeding, a history of breast or uterine cancer, or if you have ever had a heart attack, stroke, or a blood clot.

Estradiol may increase your risk of developing a condition that may lead to uterine cancer. Your doctor may prescribe a progestin while you are using estradiol, to help lower this risk. Report any unusual vaginal bleeding right away.

Long-term use of estradiol may increase your risk of breast cancer, heart attack, stroke, or blood clot. Talk with your doctor about your individual risks before using estradiol transdermal long term.

Have regular physical exams and self-examine your breasts for lumps on a monthly basis while using estradiol transdermal.

Estradiol transdermal should not be used to prevent heart disease, stroke, or dementia, because this medicine may actually increase your risk of developing these conditions.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For estradiol, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to estradiol or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of estradiol transdermal patch, gel, and spray is not indicated in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of estradiol transdermal patch, gel, and spray have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have breast cancer, stroke, or dementia, which may require caution in patients receiving estradiol transdermal patch, gel and spray.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

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 estradiol, 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 estradiol 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 estradiol 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.

• Aprepitant
• Bosentan
• Bupropion
• Carbamazepine
• Ceritinib
• Conivaptan
• Dabrafenib
• Darunavir
• Dexamethasone
• Donepezil
• Eliglustat
• Enzalutamide
• Fosphenytoin
• Griseofulvin
• Idelalisib
• Isotretinoin
• Lesinurad
• Lixisenatide
• Lumacaftor
• Mitotane
• Modafinil
• Netupitant
• Oxcarbazepine
• Phenytoin
• Pitolisant
• Pixantrone
• Prednisone
• Rifabutin
• Rifampin
• St John's Wort
• Sugammadex
• Theophylline
• Tizanidine
• Topiramate
• Valproic Acid

Using estradiol 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.

• Alprazolam
• Amprenavir
• Atazanavir
• Bacampicillin
• Betamethasone
• Bexarotene
• Clarithromycin
• Colesevelam
• Cyclosporine
• Delavirdine
• Efavirenz
• Fosamprenavir
• Fosaprepitant
• Ginseng
• Ketoconazole
• Lamotrigine
• Levothyroxine
• Licorice
• Mycophenolate Mofetil
• Mycophenolic Acid
• Nelfinavir
• Prednisolone
• Rifapentine
• Ritonavir
• Rosuvastatin
• Rufinamide
• Selegiline
• Tacrine
• Telaprevir
• Tipranavir
• Troglitazone
• Troleandomycin
• Voriconazole
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using estradiol with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use estradiol, or give you special instructions about the use of food, alcohol, or tobacco.

• Caffeine

Other Medical Problems

The presence of other medical problems may affect the use of estradiol. Make sure you tell your doctor if you have any other medical problems, especially:

• Abnormal or unusual vaginal bleeding or
• Blood clots (eg, deep vein thrombosis, pulmonary embolism), active or history of or
• Breast cancer, known or suspected, or history of or
• Heart attack, active or recent (within the past 12 months) or
• Liver disease or
• Protein C or protein S deficiency, or other known blood clotting disorders or
• Stroke, active or recent (within the past 12 months) or
• Surgery with a long period of inactivity or
• Tumors (estrogen-dependent), known or suspected—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
• Heart 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 using hormonal therapy in the past or
• Liver tumors or
• Migraine headache or
• Porphyria (an enzyme problem) or
• Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.

It is very important that your doctor check your progress at regular visits to make sure estradiol is working properly and does not cause unwanted effects. Pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise.

It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using estradiol 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 estradiol may increase your risk for having 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 greater if you have high blood pressure, high cholesterol in your blood, diabetes, or if you are overweight or smoke cigarettes. Contact your doctor immediately if you experience confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.

Using estradiol over a long period of time may increase your risk of breast cancer, endometrial cancer, or uterine cancer. Talk with your doctor about this risk. If you still have your uterus (womb), ask your doctor if you should also use a progestin medicine. Check with your doctor if you have unusual vaginal bleeding.

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

Using estradiol may increase your risk for gallbladder disease. Talk with your doctor about this risk.

Tell the medical doctor or dentist in charge that you are using estradiol before any kind of surgery (including dental surgery) or emergency treatment. Your doctor will decide whether you should continue using estradiol. estradiol may also affect the results of certain medical tests.

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

estradiol may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis 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 you are using estradiol.

Check with your child's doctor right away if your child starts to have the following symptoms: nipple or breast swelling or tenderness in females, or enlargement of the breasts in males. Your child may have been exposed to estradiol.

Do not allow your pets to lick or touch the arm where estradiol was applied. Small pets may be sensitive to estradiol. Call your pet's veterinarian if your pet starts to have the following symptoms: 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 (eg, St. John's wort) or vitamin supplements.

Before using estradiol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: vaginal bleeding of unknown cause, certain cancers (such as breast cancer, cancer of the uterus/ovaries), blood clots, stroke, heart disease (such as heart attack), liver disease, kidney disease, family medical history (especially breast lumps, cancer, blood clots, angioedema), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, diabetes, high cholesterol/triglyceride levels, obesity, lupus, underactive thyroid (hypothyroidism), mineral imbalance (low or high level of calcium in the blood), a certain hormone problem (hypoparathyroidism), uterus problems (such as fibroids, endometriosis), gallbladder disease, asthma, seizures, migraine headaches, mental/mood disorders (such as dementia, depression), a certain blood disorder (porphyria).

Do not smoke or use tobacco. Estrogens combined with smoking further increases your risk of stroke, blood clots, high blood pressure, and heart attack, especially in women older than 35.

Tell your doctor if you just had or will be having surgery, or if you will be confined to a chair or bed for a long time (such as a long plane flight). These conditions increase your risk of getting blood clots, especially if you are using an estrogen product. You may need to stop this medication for a time or take special precautions.

This drug may cause blotchy, dark areas on your face and skin (melasma). Sunlight may worsen this effect. Limit your time in the sun. Avoid tanning booths and sunlamps. Wear protective clothing when outdoors. Ask your doctor or pharmacist about using sunscreen with this medication. Sunscreen may affect the absorption of this medication if applied on the area of the skin where the medication was applied.

If you are nearsighted or wear contact lenses, you may develop vision problems or trouble wearing your contact lenses. Contact your eye doctor if these problems occur.

This product is not meant for children. See the Warning section about the risks to children if they are accidentally exposed to this medication.

This medication must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor right away.

This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breast-feeding.