Estradot

Introduction: What is ESTRADOT?

ESTRADOT is a patch that is applied to the skin. It is available in five sizes, each containing and releasing different amounts of estradiol, as follows: ESTRADOT 25: 2.5 cm² patch, containing 0.39 mg estradiol (as hemihydrate) and releasing about 25 μg estradiol per day; ESTRADOT 37.5: 3.75 cm² patch, containing 0.585 mg estradiol (as hemihydrate) and releasing about 37.5 μg estradiol per day; ESTRADOT 50: 5.0 cm² patch, containing 0.78 mg estradiol (as hemihydrate) and releasing about 50 μg estradiol per day; ESTRADOT 75: 7.5 cm² patch, containing 1.17 mg estradiol (as hemihydrate) and releasing about 75 μg estradiol per day; ESTRADOT 100: 10 cm² patch, containing 1.56 mg estradiol (as hemihydrate) and releasing about 100 μg estradiol per day.

ESTRADOT patches are applied twice weekly. Each patch should be worn continuously for 3 to 4 days.

When ESTRADOT is applied to the skin, the patch releases small amounts of estradiol, which passes directly through the skin into your bloodstream. Estradiol is the same as the natural hormone that is produced by your ovaries in large quantities before menopause (the time when your menstrual periods stops).

The use of Hormone Replacement Therapy (HRT) should be done under your doctor's supervision, with a regular follow-up (at least once a year) to identify the adverse events associated with long-term treatment.

If you want to know more or have any questions, please ask your doctor or pharmacist.

Uses of ESTRADOT (estrogen)

1. ESTRADOT (estradiol-17ß) is indicated for the relief of menopausal and postmenopausal symptoms:

   Your body normally makes estrogens and progestins (female hormones) mainly in the ovaries. Between ages 45 and 55, the ovaries gradually stop making estrogens. This leads to a decrease in body estrogen levels and a natural menopause (the end of monthly menstrual periods). If both ovaries are removed during an operation before natural menopause takes place, the sudden decrease in estrogen levels causes "surgical menopause".

   Menopause is not a disease; it is a natural life event and different women experience menopause and its symptoms differently. Not all women suffer obvious symptoms of estrogen deficiency. When the estrogen levels begin decreasing, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating (“hot flashes” or “hot flushes”). Using estrogen drugs can help the body adjust to lower estrogen levels and reduce these symptoms.

2. ESTRADOT is also indicated for the prevention of osteoporosis due to a lack of estrogens occurring naturally or caused by a surgery, in addition to other important therapeutic measures such as adequate diet, calcium and vitamin D intake, cessation of smoking and regular weight-bearing exercise. In postmenopausal women already diagnosed as having osteoporosis and vertebral fractures, treatment with ESTRADOT may retard further bone loss. For the prevention of osteoporosis, you should also consider alternative therapies with your doctor.

   Osteoporosis is a thinning of the bones that makes them weaker and allows them to break more easily. In osteoporosis, the bones of the spine, wrists and hips break most often. The bones of both men and women start to thin after about age 40, but women lose bone faster after menopause. Using estrogens after menopause slows down bone thinning and may prevent bones from breaking. Lifelong adequate calcium intake, either in the diet (such as dairy products) or by taking calcium supplements (to reach a total daily intake of 1000-1500 milligrams per day), and certain types of exercise may help to prevent osteoporosis. Before you change your calcium intake or exercise habits, it is important to discuss these lifestyle changes with your doctor to find out if they are safe for you.

   Some women are more likely to develop osteoporosis after menopause than others. You and your doctor should discuss the benefits and risks of ESTRADOT. If you have been prescribed ESTRADOT only for the prevention of osteoporosis you should discuss other alternative therapies with your doctor.

Uses of Progestins

If you have not had a hysterectomy (operation to remove the womb), estrogens should be prescribed in association with a progestin.

Progestins used in hormone replacement therapy have similar effects to the female sex hormone progesterone. During the childbearing years, progesterone is responsible for regulation of the menstrual cycle. The estradiol delivered by ESTRADOT not only relieves your menopausal symptoms, but, like estrogens produced by your body, may also stimulate growth of the inner lining of the uterus, the endometrium. In menopausal and postmenopausal women with an intact uterus, stimulation of growth of the endometrium may result in irregular bleeding. In some cases this may progress into a disorder of the uterus known as endometrial hyperplasia (overgrowth of the lining of the uterus). The development of estrogen-mediated disorders of the uterus can be reduced if a progestin is given regularly for a certain number of days with your estrogen replacement therapy. Each cycle of progestin administration should induce a periodic bleeding, whereby the inner lining of the uterus is regularly shed, thus protecting against endometrial hyperplasia.

If your uterus has been surgically removed, endometrial hyperplasia cannot occur and cyclical administration of a progestin is not necessary (except if your uterus has been removed and you have residual endometriosis).

Restrictions on Use: Who Should not Take ESTRADOT?

Certain medical conditions may be aggravated by estrogens, therefore estrogens should either not be used at all or should be used with precaution under these conditions.

ESTRADOT should not be used under these conditions:

• if you are pregnant or think you may be pregnant. Since pregnancy may be possible early in menopause while you are still having spontaneous periods, the use of non-hormonal birth control should be discussed with your physician at this time. If you take estrogen during pregnancy, there is a small risk of your unborn child having birth defects.

• if you are breast-feeding. Ask your doctor or pharmacist for advice.

• if you currently have or have ever had cancer of the breast, uterus or endometrium (lining of the womb) or any other cancer which is sensitive to estrogens

• if you have been diagnosed with endometrial hyperplasia (overgrowth of the lining of the uterus)

• if you have unexplained changes in vaginal bleeding

• if you have active phlebitis (inflamed varicose veins)

• if you currently have a problem with blood clots forming in your blood vessels or have ever had such a problem in the past. This may cause painful inflammation of the veins (thrombophlebitis) or blockage of a blood vessel in the legs (deep vein thrombosis), lungs (pulmonary embolism) or other organs.

• if you have ever had a heart attack, stroke or coronary heart disease

• if you currently have a severe liver disease

• if you have migraine or severe headaches

• if you have had partial or complete loss of vision due to blood vessel disease in the eye

• if you have a disease of blood pigment called porphyria

• if you have ever had any unusual allergic reaction to estradiol or any other component of the patch (see What Does ESTRADOT Contain?).

Talk to your doctor if you have any further questions or if you think that any of the above may apply to you.

ESTRADOT and children: ESTRADOT should not be used in children.

Warnings and Precautions

Although estrogens provide health benefits, certain precautions should be taken before their use and in some situations their use may not be appropriate. See your doctor at least once a year for check-ups. Some women will need to go more often. You should discuss with your doctor the need for adjusting or continuing therapy.

Endometrial hyperplasia and endometrial carcinoma: If your uterus has not been removed, estrogen-only therapy can increase the risk of endometrial hyperplasia (overgrowth of the lining of the uterus). It has been shown that adequate addition of progestin therapy to estrogen therapy lowers the incidence of endometrial hyperplasia (see Uses of Progestins:).

The use of estrogens has been reported to increase the risk of cancer of the lining of the uterus (endometrial cancer) in women after the menopause. It has been shown that adequate concomitant progestogen therapy lowers the incidence of endometrial hyperplasia and therefore the potential risk of endometrial carcinoma associated with prolonged use of estrogen therapy. If you have not had a hysterectomy (operation to remove the womb), your doctor will give you medicine containing another hormone called progestogen to offset the effects of estrogens on the lining of the womb. Your doctor will explain to you how to take these tablets. If you have had your uterus removed by a hysterectomy, uterine cancer would not be a risk for you and cyclical administration of a progestin is not necessary.

Breast cancer: Women with a family history of breast cancer, or with breast nodules, fibrocystic breast disease (lumps), or abnormal mammograms should consult with their doctor before starting hormone replacement therapy. Your doctor will check your breasts and your pelvis. Regular breast examinations by a health professional and monthly self-examination are recommended for all women. This helps to monitor for unwanted effects of HRT. Tell your doctor if you suspect any abnormality. The overall benefits and possible risks of hormone replacement therapy should be discussed with the physician.

Venous thromboembolism: A recent study indicated that the use of estrogen with or without progestin is associated with an increased risk of developing venous thromboembolism (blood clots in the veins). Make sure you tell your doctor if you think you may be at increased risk of formation of blood clots in your blood vessels. The risk increases with age and may also be increased:

• if you or anyone in your immediate family has ever had blood clots in the blood vessels of the legs or lungs

• if you have varicose veins

• if you have systemic lupus erythematosus (a connective tissue disease)

• if you are overweight

• if you smoke

Tell your doctor well in advance of any expected hospitalization or surgery. If you have to go into hospital unexpectedly, tell the doctor who admits you that you are using ESTRADOT. The risk of developing blood clots in your blood vessels may be temporarily increased as a result of an operation, serious injuries or having to stay in bed for a prolonged period. ESTRADOT should not be restarted until you are fully mobile.

Stroke and cardiac disease: A recent study indicated that the use of estrogen with or without progestin is associated with an increased risk of stroke and coronary heart disease. Before starting an estrogen therapy, you should discuss the benefits and risks with your doctor.

Gallbladder disease: The use of oral estrogens after menopause has been reported to increase the risk of gallbladder disease requiring surgery.

Dementia: Recent studies indicate that the use of combined estrogen and progestin in women aged 65 and older may increase the risk of developing probable dementia (decline in memory or mental ability).

Ask your doctor or pharmacist to answer any questions you may have.

Take Special Care with ESTRADOT

Before you start using ESTRADOT, you will discuss with your doctor your personal medical history and that of your family. You will also be given a complete physical and gynecological examination. You may be advised to have a mammogram prior to the start of your treatment and at regular intervals during treatment, as deemed appropriate by your doctor. To help your doctor decide whether you should use ESTRADOT and what precautions should be taken during use, tell your doctor:

• what other prescription and nonprescription medicines, if any, you are taking. There are some medicines which interfere with the effects of estrogens.

• about any allergies or sensitivities to medicines or any other substances you may have

• if you are undergoing surgery or need long bed rest

• if you currently have or have ever had any of the following:

  • high blood pressure

  • phlebitis (inflamed varicose veins)

  • abnormal blood clotting

  • heart, kidney, or liver problems

  • porphyria (an inherited condition where breakdown of hemoglobin, a component of blood cells, is impaired)

  • systemic lupus erythematosus

  • asthma

  • gall bladder disease

  • abnormalities of the breast (such as lumps) or uterus

  • endometriosis (disorder of the pelvis causing painful menstrual periods)

  • uterine fibroids or other benign tumors of the womb

  • breast cancer in your immediate family

  • breast disease, breast biopsies (removal and examination of breast tissue sample)

  • epilepsy or other neurological disorders (disorders of brain and/or nervous system)

  • migraine

  • depression

  • diabetes

  • high levels of lipid in your blood

  • jaundice or itching related to estrogen use or during pregnancy

  • otosclerosis (hearing loss due to a problem with bones in the ear)

Your doctor may want to take special precautions if you have any of these conditions.

Adverse Effects

All medicines can have side effects. Sometimes they are serious, most of the time they are not.

Tell your doctor immediately and remove the patch if any of the following occurs:

• signs of heart attack: chest pain, dizziness, nausea, shortness of breath, irregular pulse

• signs of stroke: collapse, numbness or weakness of the arms and the legs, headache, dizziness and confusion, visual disturbance, difficulty swallowing, slurred speech and loss of speech

• signs of an allergic reaction: sudden troubled breathing, tightness of the chest, general rash, swelling or itching

• signs that blood clots may have formed in your body: pain or heaviness in the calves, legs, thighs or chest, sudden shortness of breath, coughing blood or dizziness

• signs of jaundice: yellowing of the eye or skin

• tender or painful inflammation of the veins

The above side effects are serious and require urgent medical attention. These side effects are rare.

Check with your doctor as soon as possible if any of the following occur:

• swelling of the lower legs, ankles, fingers or abdomen due to fluid retention (oedema)

• change in weight

• change in your sex drive

• easy bruising, excessive nose bleeds, excessive heavy periods (may be signs of abnormal blood clotting)

• irregular vaginal bleeding

• lower abdominal pain or swelling, painful and/or heavy periods (may be signs of growth of fibroids in the uterus)

• change in vaginal discharge (may be a sign that too much estrogen is taken)

• vaginal thrush (vaginal fungal infection with severe itching, vaginal discharge)

• intolerable breast tenderness

• breast enlargement or lumps

• increase in blood pressure

• persistent or severe skin irritation

• redness, rash, or itching of the skin after the patch has been removed; hair loss, excessive hairiness

• spotty darkening of the skin, particularly on the face (chloasma)

• depression, headache, migraine, decline of memory or mental ability, dizziness, uncontrollable jerky movements (chorea)

• changes in vision

• contact lens discomfort

• hearing loss

• nausea, vomiting, cramps in the abdomen, tender abdomen (may be signs of gallbladder disease), fluid retention or bloating persisting for more than 6 weeks

• gall bladder disease (tendency to form gall stones)

• upper abdominal pain or swelling (may be signs of liver tumors)

In addition, ESTRADOT may produce some redness or irritation under or around the patch in some women (see Helpful Hints:).

Tell your doctor if you notice any unusual symptoms.

How Long to Use ESTRADOT?

ESTRADOT should be used only as long as needed. This will help to control your symptoms and prevent bone loss after the menopause.

Periodically (at least yearly), you should discuss with your doctor the possible risks and benefits associated with HRT and whether you still need the treatment.

Women who use HRT may have an increased risk of developing blood clots, breast cancer, cancer of the uterus (womb), heart disease and stroke, or probable dementia (decline of memory or mental ability).

If you have not had a hysterectomy (operation to remove the womb), your doctor should give you tablets containing another type of hormone called progestogen to take in addition to the patches to reduce the risk of cancer of the uterus. Withdrawal bleeding may occur at the end of the progestogen treatment period. Tell your doctor if you experience irregular and/or heavy bleeding.

Women taking estrogens alone for a long time may have a higher risk of developing ovarian cancer than women not using estrogens. The association between ovarian cancer and ESTRADOT is not known.

You and your doctor should discuss these risks and benefits, taking into account your personal medical status.

How to Use ESTRADOT

Follow all instructions given to you by your doctor or pharmacist carefully. Your doctor will explain when to start using ESTRADOT. ESTRADOT is used as continuous therapy. You will need to wear a patch all the time. The ESTRADOT patches are applied twice weekly on the same days of each week. Each patch should be worn continuously for 3 to 4 days.

Each box contains 8 ESTRADOT patches. If your treatment is for less than 28 days of estrogen (cyclical therapy), you will have 1 or 2 patches left over which can be used for the next month.

It is important that you take your medication as your physician has prescribed. Do not discontinue or change your therapy without consulting your physician first.

Taking Other Medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. Remember also those not prescribed by a doctor.

This particularly includes the following: anti-anxiety medicines (e.g.barbiturates, meprobamate), anti-epileptic medicines (e.g. pheno barbital, phenytoin or carbamazepine), an anti-inflammatory medicine called phenylbutazone, antibiotics and other anti-infective medicines (e.g. rifampicin, rifabutin, nevirapine, efavirenz), and herbal medicines (e.g. St. John's wort).

These medicines may be affected by ESTRADOT or, conversely, they may affect how well ESTRADOT works. Your doctor may need to adjust the dose of your treatment.

How ESTRADOT Works?

The main estrogen produced by your ovaries prior to menopause is estradiol, and this is the same estrogen that is in ESTRADOT. When applied to the skin, the ESTRADOT patch continually releases small, controlled quantities of estradiol, which pass through your skin and into your bloodstream. The amount of estrogen prescribed depends on your body's needs. Your doctor may adjust the amount you get by prescribing another (different) patch size.

By providing estradiol, ESTRADOT offers relief from menopausal symptoms.

How and Where to Apply ESTRADOT? (see package insert for illustrations)

It is recommended that you change the site of application each time the patch is applied. However, each time you apply a patch you should always apply it to the same area of your body (i.e., if the patch is applied to the buttocks, move the patch from right side to left side, twice a week or more if there is any redness under the patch).

1. Preparing the Skin: In order for the patch to stick, the skin should be clean, dry and free of creams, lotions or oils. If you wish, you may use body lotion after the patch has been properly applied to the skin. The skin should not be irritated or broken, since this may alter the amount of hormone you get. Contact with water (bath, pool, or shower) won't affect the patch, although very hot water, or steam, may loosen it and therefore should be avoided (see Helpful Hints:).

2. Where to Apply the ESTRADOT Patch: The ESTRADOT patch is rounded rectangular.

   The buttock is the preferred place to apply the patch. Other suitable application sites are the sides, hip, lower back or lower abdomen. Change the site of application each time you put a patch on. You can use the same spot more than once but not twice in a row.

   Avoid areas of the skin where clothing may rub the patch off or areas where the skin is very hairy or folded. Also avoid areas where the patch is likely to be exposed to the sun since this may affect how the patch works.

   Do not apply ESTRADOT to your breast, since this may cause unwanted effects and discomfort.

3. Opening the Pouch: Each ESTRADOT patch is individually sealed in a protective pouch. Tear open this pouch at the indented notch and remove the patch. Do not use scissors, as you may accidentally cut and destroy the patch.

4. Removing the Liner: One side of the patch has the adhesive that sticks to your skin. The adhesive is covered by a protective liner that must be removed.

   To separate the patch from the liner, hold the patch with the protective liner facing you. Peel off one half of the protective liner and discard it. Try to avoid touching the sticky side of the patch with your fingers.

   Using the other half of the liner as a handle, apply the sticky side of the system to a dry area of intact skin on the trunk of the body. Press the sticky side on the skin and smooth down.

   Fold back the remaining side of the edge of the protective liner and pull it across the skin. Avoid touching the adhesive.

   Don't worry if the patch buckles slightly because you can flatten it out after the liner has been removed. Apply the patch soon after opening the pouch and removing the liner.

5. Applying the ESTRADOT Patch: Apply the adhesive side to the spot you have chosen. Press it firmly in place with the palm of your hand for about 10 seconds, then run your finger around the edge, making sure there is good contact with the skin.

6. When and How to Remove the Patch: The ESTRADOT patch should be changed twice weekly. Always change it on the same 2 days of the week. If you forget to change it at the scheduled time, there is no cause for alarm. Just change it as soon as possible and continue to follow your usual schedule.

   After you remove the patch fold it in half with the adhesive sides inwards. Throw it away, safely out of the reach of children or pets.

   Any adhesive left on your skin should rub off easily. You can also use mineral oil, baby oil or rubbing alcohol to remove adhesive from the skin. Apply a new ESTRADOT patch on a different spot of clean, dry skin.

7. If you Forget to Use ESTRADOT: If you miss applying a patch, apply a new patch as soon as you remember. No matter what day that happens, go back to changing this patch on the same day as your initial schedule.

Helpful Hints

What to do if the patch falls off? Should a patch fall off in a very hot bath or shower, shake the water off the patch. Dry your skin completely and reapply the patch (to a new area of skin) and continue your regular schedule. Make sure you choose a clean, lotion-free area of the skin. If it still does not stick completely to your skin, then use a new patch. No matter what day this happens, go back to changing the patch on the same days as the initial schedule.

If hot baths, saunas or whirlpools are something you enjoy and you find that the patch is falling off, you may consider removing the patch temporarily while you are in the water. If you do remove the patch temporarily, the adhesive side of the patch should be placed on the protective liner that was removed when originally applying the patch. Wax paper may be used as an alternate to the liner. This prevents the contents of the patch from emptying by evaporation while you are not wearing it.

In addition to exposure to very hot water, there are some other causes for the patch failing to stick. If you are having patches fall off regularly, this could be happening as a result of:

• using any type of bath oil

• using soaps with a high cream content

• using skin moisturizers before applying the patch

Patch adhesion may be improved if you avoid using these products, and by cleansing the site of application with rubbing alcohol before you apply the patch.

What to do if your skin becomes red or irritated under or around the patch? As with any product that covers the skin for a period of time (such as bandages), the ESTRADOT patch can produce some skin irritation in some women. This varies according to the sensitivity of each woman.

Usually this redness does not pose any health concern to you, but to reduce this problem, there are some things that you may do:

• Choose the buttock as the site of application.

• Change the site of application of the ESTRADOT patch every time a new patch is applied, usually twice weekly.

Experience with another matrix patch (Vivelle) has shown that if you allow the patch to be exposed to the air for approximately 10 seconds after the protective liner has been removed, skin redness may not occur.

If redness and/or itching continues, you should consult your physician.

Always Remember

Your doctor has prescribed ESTRADOT for you after a careful review of your medical needs. Use it only as directed and do not give it to anyone else. Your doctor should re-examine you at least once a year.

If you have any questions, contact your doctor or pharmacist.

Symptoms and Treatment of Overdosage

Symptoms: Overdosage with estrogen may cause nausea, breast discomfort, fluid retention, bloating or vaginal bleeding in women.

Treatment: Owing to the mode of administration (transdermal), plasma levels of estradiol-17ß can be rapidly reduced by removal of the patch.

What Does ESTRADOT Contain?

Like most medicines, ESTRADOT contains other substances in addition to estrogen. In addition to the active ingredient (estradiol-17β), the ESTRADOT patch contains: acrylic adhesive, silicone adhesive, oleyl alcohol, povidone and dipropylene glycol.