Estalis 140/50 mcg: Uses, Side Effects and Dosage

Serious Warnings and Precautions

What is ESTALIS used for?

• ESTALIS should only be used if you have a uterus (it has not been surgically removed) to reduce moderate or severe menopausal symptoms.
• To treat vulval and vaginal atrophy (itching, burning or dryness in or around the vagina, difficulty or burning on urination).

You should carefully discuss the risks and benefits of hormone replacement therapy (HRT) with your healthcare professional. You should regularly talk with your healthcare professional about whether you still need treatment with HRT.

How does ESTALIS work?

Treatment with ESTALIS offers relief from menopausal symptoms for women with uteri. With ESTALIS used in a continuous regimen, you receive estradiol and norethindrone acetate (NETA), a progestin, throughout the entire 28-day cycle. The progestin provides important protection for your uterus.

Uses of Estrogens

The main estrogen produced by your ovaries prior to menopause is estradiol, and this is the same estrogen that is in ESTALIS. When applied to the skin, the ESTALIS patches continually release 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. By providing estradiol, ESTALIS offer relief from menopausal 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.

Uses of Progestins

Progestins used in hormone replacement therapy have similar effects to the female sex hormone progesterone. During the child bearing years, progesterone is responsible for regulation of the menstrual cycle. The estradiol delivered by ESTALIS 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 intact uteri, 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), which increases the risk of endometrial cancer (cancer of the lining of the uterus). The development of estrogen-mediated disorders of the uterus can be reduced if a progestin, such as norethindrone acetate, is given regularly for a certain number of days with your estrogen replacement therapy. For women receiving ESTALIS in a continuous combined regimen, it is expected that uterine bleeding will stop within a period of a few months and such treatment should also be protective of endometrial hyperplasia.

What are the ingredients in ESTALIS?

Medicinal ingredients: estradiol (an estrogen hormone) USP and norethindrone acetate (NETA – a progesterone hormone) USP.

Non-medicinal ingredients: a silicone and acrylic -based multipolymeric adhesive, povidone USP, oleic acid NF, and dipropylene glycol.

ESTALIS comes in the following dosage forms:

ESTALIS packs contain 8 patches. ESTALIS (NETA/17ß-estradiol) patches are available in two strengths: ESTALIS 140/50 and ESTALIS 250/50.

ESTALIS 140/50: 9 cm² patch, containing 2.7 mg of norethindrone acetate and 0.62 mg estradiol and releasing 140 mcg of norethindrone acetate and 50 mcg of estradiol per day.

ESTALIS 250/50: 16 cm² patch, containing 4.8 mg of norethindrone acetate and 0.51 mg estradiol and releasing 250 mcg of norethindrone acetate and 50 mcg of estradiol per day.

Do not use ESTALIS if:

• you are allergic to estradiol, norethindrone acetate or any of the non-medicinal ingredients in ESTALIS or a component of the container (see What are the ingredients in ESTALIS?)

• you are pregnant or think you may be pregnant. Since pregnancy may be possible early in menopause while you are still having spontaneous periods, you should talk to your healthcare professional about using non-hormonal birth control. If you take estrogen during pregnancy, there is a small risk of your unborn child having birth defects.

• you are breastfeeding. Talk to your healthcare professional about how to fed your baby.
• you have or have a history of cancer of the breast, or uterus or endometrium (lining of the womb) or any other cancer which is sensitive to estrogen
• you have been diagnosed with overgrowth of the lining of the uterus (endometrial hyperplasia)
• you have unusual vaginal bleeding without a known reason
• you have inflamed varicose veins (thrombophlebitis)
• you have or have a history of blood clots in legs or somewhere else in your body
• you have or have a history of heart attack, stroke or coronary heart disease (including angina pectoris)
• you have serious liver disease
• you have or have a history of migraines
• you have had partial or complete loss of vision due to blood vessel disease in the eye
• you have a disease of blood pigment called porphyria

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take ESTALIS. Talk about any health conditions or problems you may have, including if you:

• have a history of severe allergic reaction or intolerance to any medications or other
• have been told that you have a condition called hereditary or acquired angioedema or if you have had episodes of rapid swelling of the hands, feet, face, lips, eyes, tongue, throat (airway blockage) or digestive tract
• have a history of breast disease (including breast lumps) and/or breast biopsies, or a family history of breast cancer
• have uterine fibroids or endometriosis
• have or 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 high blood pressure
• have a family history of blood clots, heart disease or stroke
• have inflamed varicose veins (phlebitis)
• have had several miscarriages
• have kidney problems
• have asthma
• have a history of bone disease (this includes certain metabolic conditions or cancers that can affect blood levels of calcium and phosphorus)
• have or have a family history of diabetes
• have systemic lupus erythematous. This is a disease of the immune system that affects the joints, skin, kidneys, blood cells, brain, heart and lungs.
• have gall bladder disease
• have a history of depression
• have hearing loss due to otosclerosis. This is a condition caused by abnormal bone growth in the middle ear.
• have a history of epilepsy (seizures) or other neurological disorders
• have high cholesterol or high triglycerides
• have had a hysterectomy (surgical removal of the uterus)
• smoke
• are undergoing surgery or need long bed rest
• have hypothyroidism. This is a condition in which your thyroid gland does not produce enough thyroid hormone.

Other warnings you should know about:

Cancer:

• 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 with or without progestins 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 lumps, breast biopsies or abnormal mammograms (breast x-rays) should talk to their healthcare professional before starting hormone replacement therapy.

  Women should have a mammogram before starting HRT and at regular intervals during treatment as recommended by their healthcare professional.

  Regular breast examinations by a healthcare professional and regular breast self-examinations are recommended for all women. You should review techniques for breast self-examination with your healthcare professional.

• 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.

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).

The purpose of adding a progestin medication to estrogen therapy is to reduce the risk of endometrial hyperplasia.

You should discuss progestin therapy and risk factors for endometrial hyperplasia and endometrial carcinoma with your healthcare professional. You should also report any unexpected or unusual vaginal bleeding to your healthcare professional.

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.

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 healthcare professional 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 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.

Check-ups and Tests:

ESTALIS should be used only under the supervision of a healthcare professional, with regular follow-up visits, at least once a year, to check for side effects associated with its use. Your first follow-up visit should be within 3 to 6 months of starting treatment. Your visit may include a blood pressure check, a breast exam, a Pap smear and pelvic exam. You should have a mammogram before starting treatment and at regular intervals as recommended by your healthcare professional. Your healthcare professional may recommend some blood tests.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with ESTALIS:

• aminoglutethimide with medroxyprogesterone acetate (MPA), often used together for the treatment of breast cancer
• medicines used to help you relax or sleep such as meprobamate, temazepam, barbiturates
• medicines used to prevent organ rejection such as cyclosporin
• medicines used for the treatment of epilepsy such as phenobarbital, phenytoin, carbamazepine, lamotrigine
• medicines used to treat fever, pain or inflammation such as phenylbutazone, acetaminophen, salicylic acid
• medicines used to treat bacterial infections such as erythromycin
• medicines used in the treatment of tuberculosis such as rifampicin, rifabutin
• medicines used for the treatment of HIV and AIDS such as nevirapine, efavirenz, ritonavir, nelfinavir
• medicines used to treat fungal infections such as ketoconazole
• herbal products containing St John’s wort (Hypericum perforatum) used to treat depression and other conditions
• morphine, used for the treatment of severe pain
• prednisone, a corticosteroid used to treat a variety of conditions including allergies and inflammation
• medicines used to treat lung and breathing problems such as theophylline
• some nutritional supplements such as vitamin C
• medicines used to lower cholesterol such as atorvastatin, clofibric acid
• medicines used to thin the blood and prevent blood clots
• medicines used to lower high blood pressure
• insulin and other medicines used to treat diabetes such as troglitazone

• alcohol

Tell your healthcare professional that you are being treated with ESTALIS if you are going to have laboratory tests. Some laboratory tests, such as tests for glucose tolerance or thyroid function, may be affected by ESTALIS therapy.

How to use ESTALIS:

1. 1. Preparing the Skin

In order for the patch to stick, the skin should be clean, dry, cool and free of any powder, moisturizer, 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) should not affect the patch (see Helpful Hints).

1. 2. Where to Apply the ESTALIS Patches

The patches may be applied to the buttocks or abdomen (see Figure 1). Change the site of application each time you put a patch on. A one week period should elapse before applying the patch to a previously used spot.

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 often if there is any redness under the patch).

Figure 1

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 THE PATCHES TO YOUR BREAST, since this may cause unwanted effects and discomfort.

1. 3. Opening the Pouch

The patches contained in ESTALIS are individually sealed in a protective pouch. Tear open this pouch at the indented notch and remove the patch (see Figure 2). Do not use scissors, as you may accidentally cut and destroy the patch.

Figure 2

1. 4. Removing the Liner

Make sure that you have removed your old patch before applying the new one.

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 side of the protective backing and discard it (see Figure 3). Try to avoid touching the sticky side of the patch with your fingers.

Figure 3

Using the other half of the backing as a handle, apply the sticky side of the patch to a dry area of your abdomen or buttocks. Press the sticky side on the skin and smooth down.

Fold back the remaining side of the patch. Grasp the straight edge of the protective backing and pull it off the patch (see Figure 4). Avoid touching the adhesive.

Figure 4

Don't worry if the patch buckles slightly. You can flatten it out after the liner has been removed.

1. 5. Applying the ESTALIS patches

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. Apply the patch soon after opening the pouch and removing the protective backing.

ESTALIS should be worn continuously until it is time to replace it with a new patch. You may wish to experiment with different locations when applying a new patch, to find sites that are most comfortable for you, where clothing will not rub against the patch.

1. 6. When and How to Remove the Patch

The ESTALIS 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 and sight 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 ESTALIS patch on a different spot of clean, dry skin.

The medicine in your patch is contained in the adhesive and not in a special reservoir.

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 as soon as possible (to a different area of skin) and continue your regular schedule. Make sure you choose a clean, dry, lotion-free area of 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 this 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 ESTALIS patches can produce some skin irritation. This varies according to the sensitivity of your skin.

Usually this redness does not pose any health concern to you, but to reduce this problem, you may change the site of application of the ESTALIS patches every time a new patch is applied.

Experience with another 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 talk to your healthcare professional.

Usual dose:

Follow all instructions given to you by your healthcare professional. Your healthcare professional will explain when to start using ESTALIS. ESTALIS is used as a continuous therapy. You will need to wear the patch all the time.

The ESTALIS patch is worn continuously for the 4 weeks of the cycle (see Figure 5). The ESTALIS patches are applied twice weekly on the same days of each week. Each patch should be worn continuously for 3-4 days.

Figure 5

The next treatment cycle is started immediately after removal of the last ESTALIS patch. Irregular uterine bleeding may occur particularly in the first 6 months, but generally decreases with time.

It is important that you take ESTALIS as your healthcare professional has prescribed. Do not discontinue or change your therapy without talking to your healthcare professional.

Overdose:

Symptoms

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

Progestin (norethindrone acetate) overdosage may cause depressed mood, tiredness, acne and hirsutism.

If you think you, or a person you are caring for, have used too much ESTALIS, contact a healthcare professional, hospital emergency department, or regional poison control centre immediately, even if there are no symptoms.

Missed Dose:

If you forget to change a patch, replace it with another patch as soon as you remember. No matter when this happens, go back to changing this patch on the day as specified on your initial schedule.

What are possible side effects from using ESTALIS?

These are not all the possible side effects you may have when taking ESTALIS. If you experience any side effects not listed here, tell your healthcare professional.

Side effects may include:

• abdominal pain, nausea, vomiting,
• back pain or menstrual period-like pain,
• breast tenderness,
• changes in vaginal discharge, vaginal infection,
• change in weight,
• headache,
• nervousness,
• pain in the extremities,
• pelvic pain,
• skin irritation,
• rash, itching, acne, dryness,
• change in your sex drive,
• painful and/or heavy periods (may be signs of fibroids (benign growths) in uterus),
• discoloration of the skin, purple skin patches,
• tingling or numbness,
• tender, red nodules under the skin (most common on the shins),
• spotty darkening of the skin, particularly on the face or abdomen (chloasma),
• easy bruising,
• excessive nose bleeds,
• sudden contraction of the womb,
• hair loss,
• excessive hairiness,
• decline of memory or mental ability,
• rapid change in mood,
• difficulty sleeping,
• contact lens discomfort,
• dry eyes,
• hearing loss.

Serious side effects and what to do about them

Serious side effects and what to do about them

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

Storage:

ESTALIS patches can be stored at room temperature (20- 25°C) up to 1 month. You may also store the patches in a refrigerator (2-8°C), in which case you should use the patches before the expiry date shown on the pack and allow them to reach room temperature before you apply them.

Do not freeze. Store in the original package.

ESTALIS patches should be kept out of the reach and sight of children and pets before and after use.

If you want more information about ESTALIS:

• Talk to your healthcare professional.
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website: (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website www.sandoz.ca, or by calling 1-800-361-3062.

Last revised: DEC 13, 2024

ESTALIS® is a registered trademark.