Estradot (Estradiol)

Usual dose:

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.

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.

What to do if the patch falls of:

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 different 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.

Overdose:

If more medication has been taken than what has been prescribed, remove the patch and contact either your doctor, hospital, or emergency department or poison control centre immediately.

Missed dose:

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.

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

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

The most common adverse drug reactions (≥1%) are: swelling of the lower legs, ankles, fingers or abdomen due to fluid retention (oedema), change in weight, vaginal bleeding or spotting and changes in vaginal discharge, headache, depression, migraine, dizziness, nausea, abdominal pain and swelling, tender breasts and breast enlargement, and persistent or severe skin irritation, redness, rash or itching of the skin after the patch has been removed (signs of application site reaction includes bleeding, bruising, burning, discomfort, dryness, skin boils, edema, erythema, inflammation, irritation, pain, tiny solid skin bumps, rash, skin discolouration, skin pigmentation, swelling, hives, and blisters).

The less common adverse drug reactions (<1%) are: change in your sex drive, hair loss, excessive hairiness, vomiting, lump or mass in the breast (possible signs of breast cancer), fibroids (benign growths in the uterus) vaginal thrush (vaginal fungal infection with severe itching, vaginal discharge).

The adverse drug reactions with unknown frequency are: easy bruising, excessive nose bleeds, spotty darkening of the skin, particularly on the face or abdomen (chloasma), purple skin patches, acne, decline of memory or mental ability, rapid mood changes, contact lens discomfort, dry eyes, gall bladder disease (tendency to form gall stones), nervousness, back pain and pain in extremity, signs or symptoms that blood clots may have formed in your body (pains in the calves, thighs or chest, sudden shortness of breath, coughing blood or dizziness), increase in blood pressure, yellowing of the eyes or the skin, diarrhea, signs of an allergic reactions (sudden troubled breathing, tightness of the chest, general rash or itching), uncontrollable jerky movements (chorea), skin inflammation and rash (rash with painful red lumps, pain in joints and muscles swelling, blistering of lips, eyes, skin peeling) breast pain, irregular heavy vaginal bleeding or constant spotting (possible signs of endometrial hyperplasia), menstrual cramps, breast discharge, lumps in the breast (non-cancerous), hives, worsening of porphyria (a condition affecting the liver), and varicose veins.

Serious Warnings and Precautions

There is an increased risk of developing invasive breast cancer, heart attack, stroke and blood clots in both lungs and large veins with the use of estrogen plus progestin therapy.

There is an increased risk of stroke and blood clots in the large veins with the use of estrogen-alone therapy.

Estrogens with or without progestins should not be used for the prevention of heart disease or stroke.

Estrogens with or without progestins should be used at the lowest effective dose and for the shortest period of time possible. Regular medical follow-up is advised.

• Breast cancer
• The results of the WHI trial indicated an increased risk of breast cancer in post-menopausal women taking combined estrogen plus progestin compared to women taking placebo.
• The results of the WHI trial indicated no difference in the risk of breast cancer in postmenopausal women with prior hysterectomy taking estrogen-alone compared to women taking placebo.
• Estrogens should not be taken by women who have a personal history of breast cancer.
• In addition, women with a family history of breast cancer or women with a history of breast lump, breast biopsies or abnormal mammograms (breast x-rays) should consult with their doctor before starting hormone replacement therapy.
• Women should have a mammogram before starting HRT and at regular intervals during treatment as recommended by their doctor.
• Regular breast examinations by a doctor and regular breast self-examination are recommended for all women. You should review technique for breast self-examination with your doctor.
• Overgrowth of the lining of the uterus and cancer of the uterus
• The use of estrogen-alone therapy by post menopausal women who still have a uterus increases the risk of developing endometrial hyperplasia (overgrowth of the lining of the uterus), which increases the risk of endometrial cancer (cancer of the lining of the uterus).
• If you still have your uterus, you should take a progestin medication (another hormone drug) regularly for a certain number of days of each month to reduce the risk of endometrial hyperplasia.
• You should discuss progestin therapy and risk factors for endometrial hyperplasia and endometrial carcinoma with your doctor. You should also report any unexpected or unusual vaginal bleeding to your doctor.
• If you have had your uterus removed, you are not at risk of developing endometrial hyperplasia or endometrial carcinoma. Progestin therapy is therefore not generally required in women who have had a hysterectomy.
• Ovarian cancer
• In some studies, the use of estrogen-alone and estrogen plus progestin therapies for 5 or more years has been associated with an increased risk of ovarian cancer.
• Heart disease and Stroke
• The results of the WHI trial indicated an increased risk of stroke and coronary heart disease in post-menopausal women taking combined estrogen plus progestin compared to women taking placebo.
• The results of the WHI trial indicated an increased risk of stroke, but no difference in the risk of coronary heart disease in post-menopausal women with prior hysterectomy taking estrogen alone compared to women taking placebo.
• Abnormal Blood Clotting
• The results of the WHI trial indicated an increased risk of blood clots in the lungs and large veins in post menopausal women taking combined estrogen plus progestin compared to women taking placebo.
• The results of the WHI trial indicated an increased risk of blood clots in the large veins, but no difference in the risk of blood clots in the lungs in post-menopausal women with prior hysterectomy taking estrogen-alone compared to women taking placebo.
• The risk of blood clots increases with age, if you or a family member has had blood clots, if you smoke or if you are severely overweight. The risk of blood clots is also temporarily increased if you are immobilized for long periods of time and following major surgery. You should discuss risk factors for blood clots with your doctor since blood clots can be life-threatening or cause serious disability.
• Gallbladder disease
• The use of estrogens by postmenopausal women has been associated with an increased the risk of gallbladder disease requiring surgery.
• Dementia
• The Women's Health Initiative Memory Study (WHIMS) was a substudy of the WHI trial and indicated an increased risk of dementia (loss of memory and intellectual function) in post-menopausal women age 65 and over taking oral combined estrogen plus progestin compared to women taking placebo.
• The WHIMS indicated no difference in the risk of dementia in post-menopausal women age 65 and over with prior hysterectomy taking oral estrogen-alone compared to women taking placebo.

Before you use ESTRADOT talk to your doctor or pharmacist if you:

• have a history of severe allergic reaction or intolerance to any medications or other substances
• have been told that you have a condition called hereditary angioedema of if you have had episodes of rapid swelling of the hands, feet, face, lips, eyes, tongue, throat (airway blockage) or digestive tract
• have a personal history of breast disease (including breast lumps) and/or breast biopsies, or a family history of breast cancer
• have experienced any unusual or undiagnosed vaginal bleeding
• have a history of uterine fibroids or endometriosis
• have a history of liver disease or liver tumours, jaundice (yellowing of the eyes and/or skin) or itching related to estrogen use or during pregnancy
• have a history of migraine headache
• have a history of high blood pressure
• have a personal or family history of blood clots, or a personal history of heart disease or stroke
• phlebitis (inflamed varicose veins)
• have a history of kidney disease or asthma
• have a history of bone disease (this includes certain metabolic conditions or cancers that can affect blood levels of calcium and phosphorus)
• have been diagnosed with diabetes
• have been diagnosed with porphyria (a disease of blood pigment)
• have been diagnosed with lupus
• gall bladder disease
• depression
• have been diagnosed with hearing loss due to otosclerosis
• epilepsy (seizures) or other neurological disorders
• have a history of high cholesterol or high triglycerides
• are pregnant or may be pregnant
• are breastfeeding
• have had a hysterectomy (surgical removal of the uterus)
• smoke
• are undergoing surgery or need long bed rest
• have had several miscarriages
• have hypothyroidism, a condition in which your thyroid gland fails to produce enough thyroid hormone and for which you are treated with thyroid hormone replacement therapy.

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

Tell your doctor or pharmacist if you are taking or have recently taken any other medications, including prescription medications, over-the-counter medications, vitamins or herbal products.

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

The following interactions with ethinyl estradiol-containing products (specifically, oral contraceptives) have been reported in the public literature. It is unknown whether such interactions occur with drug products containing other types of estrogens (like hormone replacement therapy): acetaminophen, vitamin C, aminoglutethimide with medroxyprogesterone acetate (MPA), atorvastatin, clofibric acid, cyclosporin, morphine, prednisolone, salicylic acid, temazepam, theophylline, and troglitazone.

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.