Estrasorb

• Allergan, Inc.

• Esprit Pharma, Inc.

• Graceway Pharmaceuticals, LLC.

• Medicis Pharmaceutical Corp.

• Valeant Pharmaceuticals North America LLC

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

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Estradiol falls into category X. Estradiol should now be used during pregnancy. There appears to be little or no increased risk of birth defects in children born to women who inadvertently used estrogens during early pregnancy. Talk to your doctor right away if you become pregnant while taking estradiol.

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

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

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

Topical:

The recommended starting dose of estradiol transdermal patches for the treatment of menopause symptoms or hypoestrogenism is 0.025 mg daily applied to the skin once weekly.

The recommended starting dose of estradiol transdermal spray for the treatment of menopause symptoms is 1.53 mg daily applied to the skin of the forearm once daily.

The recommended starting dose of estradiol transdermal gel for the treatment of menopause symptoms is 0.25 g daily applied to the skin of the upper thigh once daily.

The recommended starting dose of estradiol vaginal cream for the treatment of menopause symptoms is 2 to 4 g daily applied to the skin of the upper thigh once daily.

The recommended starting dose of estradiol vaginal insert for the treatment of menopause symptoms is 0.05 or 0.10 mg daily inserted into the vagina every 3 months.

Oral:

The recommended dose range of estradiol oral tablets for the treatment of menopause symptoms is 1 to 2 mg daily by mouth.

Injectable:

The recommended dose range of estradiol cypionate intramuscular injection for the treatment of menopause symptoms is 1 to 5 mg injected every 3 to 4 weeks.

The recommended dose range of estradiol valerate intramuscular injection for the treatment of menopause symptoms is 10 to 20 mg injected every 4 weeks.

You should not use this medicine if you have any of the following conditions: a history of heart attack, stroke, or blood clot (especially in your lung or your lower body), a bleeding or blood-clotting disorder, liver disease, abnormal vaginal bleeding, history of an allergic reaction to estradiol topical, or a hormone-related cancer such as breast or uterine cancer.

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

Do not use estradiol topical if you are breast-feeding a baby.

Topical estradiol is absorbed through the skin and can cause premature puberty in a child who comes into contact with this medicine or with skin where the medicine was applied. Call your doctor if a child who has close contact with you develops swollen nipples or enlarged breasts.

Children should avoid coming into contact with skin areas where you have applied estradiol topical. If contact does occur, wash with soap and water right away. Cover treated areas with clothing to protect others from coming into contact with the skin where you apply this medicine.

Estrogens will not prevent heart disease, heart attack, stroke, breast cancer, or dementia, and may actually increase your risk of developing these conditions. Estrogens may also increase your risk of uterine or ovarian cancer.

Talk with your doctor about your individual risks before using estradiol long-term. Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment.

Estrogens will not prevent heart disease, heart attack, stroke, breast cancer, or dementia, and may actually increase your risk of developing these conditions. Estrogens may also increase your risk of uterine or ovarian cancer.

Talk with your doctor about your individual risks before using estradiol long-term. Your doctor should check your progress on a regular basis (every 3 to 6 months) to determine whether you should continue this treatment.

You should not use estradiol topical if you have:

• a history of heart attack, stroke, or blood clot (especially in your lung or your lower body);
• liver disease;
• a bleeding or blood-clotting disorder;
• unusual vaginal bleeding that has not been checked by a doctor;
• any type of breast, uterine, or hormone-dependent cancer; or
• if you have ever had an allergic reaction to estradiol topical.

To make sure you can safely use estradiol topical, tell your doctor if you have any of these other conditions:

• high blood pressure, angina, or heart disease;
• high cholesterol or triglycerides;
• kidney disease;
• asthma;
• hereditary angioedema;
• epilepsy or other seizure disorder;
• migraines;
• endometriosis;
• diabetes;
• a thyroid disorder;
• depression;
• porphyria;
• lupus;
• gallbladder disease; or
• low levels of calcium in your blood.

FDA pregnancy category X. This medication can cause birth defects. Do not use estradiol topical if you are pregnant. Tell your doctor right away if you become pregnant during treatment. Use an effective form of birth control while you are using this medication.

Estradiol can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

Estradiol increases your risk of developing endometrial hyperplasia, a condition that may lead to cancer of the uterus. Taking progestins while using estradiol may lower this risk. If your uterus has not been removed, your doctor may prescribe a progestin for you to take while you are using estradiol topical.

The following serious adverse reactions are discussed elsewhere in labeling:

• Cardiovascular Disorders [see BOXED WARNING, WARNING AND PRECAUTIONS]
• Malignant Neoplasms [see BOXED WARNING, WARNING AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Table 1 summarizes the treatment-emergent adverse reactions with ESTRASORB therapy.

Table 1: Number (%) of Patients Reporting ≥ 5% Treatment-Emergent Adverse Reactions

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ESTRASORB. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Unusual bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting; dysmenorrheal; increase in size of uterine leiomyomata; vaginitis including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer, endometrial hyperplasia; endometrial cancer.

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.

Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gall bladder disease; pancreatitis, enlargement of hepatic hemangiomas.

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

Retinal vascular thrombosis, intolerance to contact lenses.

Headache, migraine, dizziness; mental depression; chorea; nervousness; mood disturbance; irritability; exacerbation of epilepsy, dementia.

Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgia; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

Read the entire FDA prescribing information for Estrasorb (Estradiol Topical Emulsion)

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Estrasorb or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Estrasorb (estradiol topical emulsion). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Table 4 summarizes the treatment-emergent adverse events with Estrasorb therapy.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy:

1. Genitourinary system. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding, spotting; dysmenorrheal; increase in size of uterine leiomyomata; vaginitis including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer, endometrial hyperplasia; endometrial cancer.

2. Breasts. Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

3. Cardiovascular. Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.

4. Gastrointestinal. Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gall bladder disease; pancreatitis, enlargement of hepatic hemagiomas.

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

6. Eyes. Retinal vascular thrombosis, intolerance to contact lenses.

7. Central Nervous System. Headache, migraine, dizziness; mental depression; chorea; nervousness; mood disturbance; irritability; exacerbation of epilepsy, dementia.

8. Miscellaneous. Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthralgia; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

(Updated November 14, 2005)

Estrasorb®
(estradiol topical emulsion)

Read this PATIENT INFORMATION before you start using Estrasorb® and read what you get each time you refill Estrasorb. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is Estrasorb®?
Estrasorb® contains an estrogen hormone called estradiol. When applied to the skin as directed below, Estrasorb® releases estradiol, which is absorbed through the skin into the bloodstream.

What is Estrasorb® used for?
Estrasorb® 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 to 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 develop 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 estrogens. In other women, symptoms can be more severe. You and your healthcare provider should talk regularly about whether you still need treatment with Estrasorb®.

Who should not use Estrasorb®?
Do not start using Estrasorb® if you:
• have unusual vaginal bleeding
• currently have or have had certain cancers
Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have had cancer, talk with your healthcare provider about whether you should use Estrasorb®.
• had a stroke or heart attack in the past year
• currently have or have had blood clots
• are allergic to Estrasorb® or any of its ingredients
See the end of this leaflet for a list of ingredients in Estrasorb®.
• think you may be pregnant.

Tell your healthcare provider:
• if you are breast feeding. The hormone in Estrasorb® can pass into you’re your breastmilk.
• about all of your medical problems. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
• if you are going to have surgery or will be on bed rest. You may need to stop using Estrasorb®.

What are the possible side effects of estrogens?
Less common but serious side effects include:
• Breast cancer
• Cancer of the uterus
• Stroke
• Heart attack
• Blood clots
• Dementia
• Gallbladder disease
• Ovarian cancer

These are some of the warning signs of serious side effects:
• Breast lumps
• Unusual vaginal bleeding
• Dizziness and faintness
• Changes in speech
• Severe headaches
• Chest pain
• Shortness of breath
• Pains in your legs
• Changes in vision
• Vomiting

Call your healthcare provider right away if you get any of these warning signs, or any other unusual symptom that concerns you.

Common side effects include:
• Headache
• Breast pain
• Irregular vaginal bleeding or spotting
• Stomach/abdominal cramps, bloating
• Nausea and vomiting
• Skin irritation, redness, or rash may occur at the site of application
• Hair loss

Other side effects include:
• High blood pressure
• Liver problems
• High blood sugar
• Fluid retention
• Enlargement of benign tumors of the uterus ("fibroids")
• Vaginal yeast infection

These are not all of the possible side effects of Estrasorb®. For more information, ask your healthcare provider or pharmacist.

What can I do to lower my chances of getting a serious side effect with Estrasorb®?
• Talk with your healthcare provider regularly about whether you should continue using Estrasorb®.
• If you have a uterus, talk to your healthcare provider about whether the addition of a progestin is right for you.
• See your healthcare provider right away if you get vaginal bleeding while using Estrasorb®.
• Have a 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 (breast x-ray examination), 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 of getting heart disease. Ask your healthcare provider for ways to lower your chances for getting heart disease.

How should I use Estrasorb®?
Estrasorb® should be used only as long as needed. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about whether you still need treatment with Estrasorb®.

Estrasorb® is an emulsion that is applied each day to the skin of both thighs and calves. It is not known if Estrasorb® will be absorbed as well if applied to other parts of the body. Estrasorb® is packaged in foil pouches. A daily dose of Estrasorb® is two foil pouches. Do not open the pouches until just before you apply Estrasorb®.

Apply Estrasorb® in the morning. If you shower or take a bath, be sure your skin is dry before using Estrasorb®. Do not apply Estrasorb® to any skin on your thighs and calves that appears to be red or irritated. Do not apply sunscreen and Estrasorb® at the same time because sunscreen may affect the amount of estradiol you absorb.

How to apply Estrasorb®
• Estrasorb® is best applied when you are sitting comfortably. The skin on both legs should be clean and dry.

• Cut or tear the first pouch across the notches to open it (Diagram 1).

• Place the pouch flat on top of your left thigh, with the open end facing your knee. Hold the other end with one hand and use the forefinger of your other hand to push all of the contents of the pouch onto your left thigh (Diagram 2).

• With one hand or both hands rub the material into your entire left thigh and left calf for three minutes or until thoroughly absorbed (Diagram 3).

Rub any excess material remaining on the hands on your buttocks.

• Cut or tear the second pouch across the notches to open it (see Diagram 1). Place the pouch flat on top of your right thigh, with the open end facing your knee. Hold the unopened end with one hand and use the forefinger of your other hand to push all of the contents of the pouch onto your right thigh (see Diagram 2).

• With one hand or both hands rub the material into your entire right thigh and right calf for three minutes until thoroughly absorbed (see Diagram 3). Rub any excess material remaining on the hands on your buttocks.

• To reduce the chances of Estrasorb® transfer to other individuals upon contact, allow the application areas to dry completely and cover with clothing.

• Wash your hands with soap and water after you have finished the applications to ensure that any excess material has been removed (Diagram 4).

If you forget to apply Estrasorb® in the morning just apply Estrasorb® as soon as you remember. Do not apply Estrasorb® more than once each day.

General information about the safe and effective use of Estrasorb®.
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Estrasorb® for conditions for which it was not prescribed. Do not give Estrasorb® to other people, even if they have the same symptoms you have. It may harm them.

Keep Estrasorb® out of the reach of children.
This leaflet provides a summary of the important information about Estrasorb®. If you would like more information, talk with your healthcare provider or pharmacist. You can ask for information about Estrasorb® that is written for health professionals. You can get more information by calling the toll free number (1-800-328-0255).

What are the ingredients in Estrasorb®?
17ß‚-estradiol, Soybean oil, Water, Polysorbate 80, Ethanol
Rx Only

Manufactured for:
Graceway Pharmaceuticals, LLC
Bristol, TN 37620

by:
Harmony Labs, Inc.
Kannapolis, NC 28083

Estrasorb® is a registered trademark of Graceway Pharmaceuticals, LLC.

I000000601   Rev. 6/09

Applies to estradiol: vaginal cream, vaginal insert extended release, vaginal tablet

Other dosage forms:

• transdermal emulsion, transdermal gel/jelly, transdermal patch extended release, transdermal spray

Along with its needed effects, estradiol (the active ingredient contained in Estrasorb) 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 while taking estradiol:

• Vaginal yeast infection

• Change in vaginal discharge
• clear or bloody discharge from the nipple
• decrease in the amount of urine
• dimpling of the breast skin
• fast heartbeat
• fever
• hives, itching, or rash
• hoarseness
• inverted nipple
• irritation
• joint pain, stiffness, or swelling
• lump in the breast or under the arm
• noisy, rattling breathing
• pain or feeling of pressure in the pelvis
• pain, redness, or swelling in the arm or leg
• persistent crusting or scaling of the nipple
• redness of the skin
• redness or swelling of the breast
• sore on the skin of the breast that does not heal
• swelling of the eyelids, face, fingers, lips, hands, feet, or lower legs
• tightness in the chest
• troubled breathing at rest
• troubled breathing or swallowing
• vaginal bleeding

Get emergency help immediately if any of the following symptoms of overdose occur while taking estradiol:

• Abdominal or stomach pain
• dizziness
• drowsiness
• nausea or vomiting
• tenderness of the breasts
• unusual tiredness or weakness

Some side effects of estradiol 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:

• Back pain
• headache
• itching or pain of the vagina or genital area
• thick, white vaginal discharge with mild or no odor
• weight gain

• Body aches or pain
• chills
• cough
• diarrhea
• ear congestion
• loss of voice
• nasal congestion
• runny nose
• sneezing
• sore throat

• Feeling sad or empty
• headache, severe and throbbing
• irritability
• lack of appetite
• tiredness
• trouble concentrating
• trouble sleeping
• welts