This medication belongs to a group of medications called hormone replacement therapy. It is a patch that contains an estrogen (estradiol-17ß) and a progestin (norethindrone).

It is used to manage menopausal and postmenopausal symptoms such as hot flushes, trouble sleeping, and vulvar and vaginal atrophy (e.g., dryness, itching, burning in or around the vagina, and difficulty or burning on urination) in women who still have their uterus intact.

Estrogen and progesterone are female hormones made by the ovaries. At menopause, the amount of estrogen made by the ovaries declines and symptoms such as hot flushes (sudden, extreme feeling of warmth) and vaginal dryness can occur. Most women reach menopause naturally around the age of 50, but some women may undergo menopause sooner, naturally or due to surgery.

When an estradiol patch is applied to your skin, it releases the hormones into your blood through your skin. The medication is designed for women who have not had a hysterectomy (removal of their uterus or womb). These women require progestin while using estrogen to prevent complications associated with taking estrogen alone.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

One 28-day treatment cycle with this medication consists of 8 patches. Each patch provides 50 µg (50 micrograms) of estradiol per day plus 140 µg or 250 µg of norethindrone per day.

One patch is applied twice weekly (change the patch every 3 to 4 days) on the same two days every week. Once the recommended sequence over a 28-day period has been completed, the next cycle starts again with a fresh package of patches.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Apply a new patch to your skin twice each week, always on the same days of the week. The patch should be applied to a clean, dry area of intact skin that is not oily, damaged or irritated, or exposed to the sun.

Apply the patch to the abdomen or buttocks. Do not apply the patch to your breasts. Avoid areas of the skin where clothing may rub the patch off or areas where the skin is very hairy or folded.

Talk to your doctor or pharmacist about the most appropriate site to apply the patch. Patches should not be applied to the same skin site twice in a row, but the patch should be applied to the same area of your body each time (i.e., change to the opposite side of the abdomen or from one buttock to the other). Allow a one-week period before applying the patch to a previously used spot.

To apply the patch:

• Choose a clean, dry area of intact skin that is not oily, damaged or irritated, or exposed to the sun. The skin should be free of powder, moisturizers, oils, and lotions.
• Tear open the patch at the notch rather than using scissors – if you accidentally cut the patch, you will not be able to use it.
• To separate the patch from the liner, hold the patch with the liner facing you and peel off one side of the protective liner and discard it. Using the other half of the liner as a handle, apply the sticky side of the patch to the selected area immediately and smooth down. Avoid touching the adhesive. Fold back the other side of the patch and remove the other side of the protective liner.
• Use your fingers to hold the patch in place for about 10 seconds and make sure that the patch is affixed to your skin, especially around its edges.

When changing the patch, remove the old one carefully, folding the adhesive side inwards, and throw it away safely out of the reach of children or pets. Any remaining adhesive on the skin can be removed with mineral oil, baby oil, or rubbing alcohol.

Bathing, showering, swimming, or other contact with water does not affect the patch. However, hot water or steam may cause the patch to loosen.

If your patch falls off, try to reapply it. If that doesn't work, apply a new patch and continue with your usual schedule. This may mean that the replacement patch will not be on your skin for as long as usual.

If you find the patch is falling off regularly in hot baths, saunas, or whirlpools, you can consider temporarily removing the patch while you are in the water.

If you remove the patch, you must cover the adhesive with the protective liner that was removed when you applied the patch, or use a piece of wax paper to stop the medication from evaporating from the patch while you are not using it.

It is important to use this medication exactly as prescribed by your doctor. If you forget to change your patch, change it as soon as you remember. If it is close to the day when you normally change your patch, still apply it but change the patch again on your usual day and continue on with your regular schedule. Do not wear 2 patches at once. If you are not sure what to do after missing a patch, contact your doctor or pharmacist for advice.

This medication may be stored in the refrigerator until you open the package. After this time, you may store the patches at room temperature, but they must be used within 6 months or before the expiry date shown on the package, whichever comes first.

If storing them in the refrigerator, allow the patch to reach room temperature before applying.

Keep this medication out of sight and reach of children and pets and protect it from direct sunlight.

140/50
Each round, 9 cm2 patch contains 140 µg of norethindrone acetate and 50 µg of estradiol-17ß. Nonmedicinal ingredients: silicone, acrylic-based adhesive, povidone, oleic acid, and dipropylene glycol.

250/50
Each round, 16 cm2 patch contains 250 µg of norethindrone acetate and 50 µg of estradiol-17ß. Nonmedicinal ingredients: silicone, acrylic-based adhesive, povidone, oleic acid, and dipropylene glycol.

Do not use this medication if you:

• are allergic to estradiol-17ß, norethindrone, or any ingredients of this medication
• are breast-feeding
• are or may be pregnant
• have or have had a stroke, heart attack, or heart disease
• have or have had blood clots in the legs, lungs, or heart
• have or have had other diseases that increase the risk of blood clots
• have endometrial hyperplasia (overgrowth of the lining of the uterus)
• have migraines with aura (headache that is associated with symptoms such as flashes of light, tingling sensations, blind spots, muscle weakness, and difficulty speaking that occur either before or during the headache)
• have or have had breast or endometrial (uterine) cancer, or other types of cancer that depend on estrogen or progestin (e.g., ovarian cancer)
• have partial or complete loss of vision or double-vision from eye disease related to circulation problems
• have porphyria (a disease of blood pigment)
• have reduced liver function or have liver disease and abnormal liver function test results
• have unexpected or unusual genital bleeding

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• acne
• back pain
• bloating
• breast tenderness
• change in sex drive
• contact lens discomfort
• discolouration of the skin or purple skin patches
• dry eyes or skin
• excessive hair growth
• hair loss
• headache
• hearing changes
• increased vaginal secretions
• memory problems
• menstrual-like pain
• nausea
• nervousness
• numbness or tingling (with no other symptoms)
• redness, itching, spots, burning and swelling underneath or around the area of the skin on which the patch is applied
• trouble sleeping
• vaginal itching with or without discharge
• weight change

Although most of the side effects listed below don't happen very often, they could lead to serious problems if you do not seek medical attention.

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

• breast lumps
• discharge from nipple
• easy bruising
• excessive nosebleeds
• flu-like symptoms
• fluid retention (swelling of the lower legs, ankles, feet, or fingers)
• high blood pressure
• intolerable breast tenderness
• itchy rash
• migraine headache
• mood changes
• pain or feeling of pressure in pelvis
• painful or heavy periods
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• symptoms of gallstones (e.g., pain in the upper right abdomen, pain between the shoulder blades or in the right shoulder)
• symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of blood clots (e.g., coughing up blood; pains in chest, groin, or leg–especially in calf of leg)
• signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
• sudden shortness of breath, coughing up blood, or sharp pain in chest
• sudden vision changes (such as partial or complete loss of vision, double vision)
• symptoms of a severe allergic reaction (e.g., hives; difficult breathing; swelling of the face, mouth, throat, or tongue)
• symptoms of a stroke (e.g., sudden and severe headache, sudden vision changes, sudden difficulty speaking, sudden weakness or numbness in arms or legs, sudden dizziness, fainting, or vomiting)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Allergy: Contact allergy is known to occur with the application of estrogen to the skin. Although it is an extremely rare event, if you develop contact allergy to any component of the medication, you may experience a severe allergic reaction with its continued use.

If you experience persistent redness or itching where the patch is applied, contact your doctor.

Blood clotting: This medication can increase the risk of blood clots in the groin, legs or lungs, heart, or brain. If you have or have had a heart attack, a stroke, heart disease, a blood clot in your leg, or have medical conditions that increase your risk of blood clots, you should not use this medication.

You may be more at risk of developing blood clots if you have severe varicose veins, severe obesity (body mass index [BMI] more than 30 kg/m2), or have a family history of blood clots. Discuss with your doctor whether any special monitoring is needed.

The risk is also increased if you are immobilized for prolonged periods and if you are having major surgery. If possible, this medication should be stopped 4 weeks before major surgery. Talk about the risk of blood clots with your doctor.

Blood pressure: This medication can increase blood pressure. If your blood pressure increases while using this medication, contact your doctor. Your doctor will check your blood pressure before you start using this medication and will monitor your blood pressure while you are using this medication.

Bone disease: If you have bone disease due to cancer or a metabolic condition causing too much calcium in your body, you should discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Breast cancer: Studies indicate an increased risk of breast cancer with long-term use of estrogen replacement therapy. If you have breast nodules, fibrocystic disease, abnormal mammograms, or a strong family history of breast cancer, you should discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Your doctor may suggest that you have a mammogram before starting this medication and at regular intervals while you are using it.

Other known risk factors for the development of breast cancer, such as not having children, obesity, early onset of menstruation, late age at first full-term pregnancy, and late age at menopause, should also be evaluated. If you are taking estrogens, you should have regular breast examinations and should learn how to do breast self-examination.

If you have or have had breast cancer, you should not use this medication.

This medication must not be applied to the breasts, as it may have harmful effects on the breast tissue.

Dementia: Those over age 65 receiving combined hormone replacement therapy (estrogen and progestin) may be at increased risk of developing dementia (loss of memory and intellectual function). If you are over 65, talk to your doctor about your concerns.

Diabetes: Estrogens may affect blood sugar control. If you have diabetes or are at risk of developing diabetes (e.g., have a family history of diabetes, have high blood pressure or high cholesterol, or are obese), carefully monitor your blood glucose levels while using this medication.

Endometrial cancer: There is evidence from several studies that estrogen replacement therapy can increase the risk of cancer of the endometrium (lining of the uterus). Taking a progestin at the right time along with an estrogen reduces this risk of endometrial cancer to the same level as that of a woman who does not take estrogen. The norethindrone (progestin) in this medication should counteract the risk of endometrial cancer.

If you develop any abnormal vaginal bleeding while using this medication, contact your doctor. If you have or have had endometrial cancer, you should not use this medication.

Fibroids: This medication may worsen fibroids, causing sudden enlargement, pain, or tenderness. If you notice these effects, contact your doctor.

Fluid retention: Estrogen may cause fluid retention and may worsen heart problems, kidney problems, or asthma. If you experience worsening of these conditions while using this medication, contact your doctor.

Follow-up examinations: It is important to have a follow-up examination 3 to 6 months after starting this medication to assess your response to treatment. Examinations should be done at least once a year after the first one.

Gallbladder disease: This medication can aggravate gallbladder disease or increase the risk of developing it. If you have gallbladder disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen (with or without progestin) for postmenopausal women. If you experience symptoms of a heart attack (chest pain, tightness or pressure, sweating, nausea, feeling of impending doom) or stroke (sudden dizziness, headache, loss of speech, changes in vision, weakness or numbness in the arms and legs) while taking this medication, get immediate medical attention.

High cholesterol or triglycerides: Estrogen may increase triglyceride levels if you already have high levels or have diabetes. This has been observed particularly when estrogen is taken orally and the risk is reduced with use of the patch. Ask your doctor if monitoring of your triglyceride levels is recommended.

Kidney function: If you have reduced kidney function, you may be more at risk of developing high blood calcium and phosphorus levels while using this medication. Discuss with your doctor whether any special monitoring is needed.

Liver function: If you have reduced liver function you should not use this medication. If you have or have had liver problems, you may require special monitoring by your doctor while you use this medication. Make sure to tell your doctor if you have ever had liver problems. Your doctor may do blood work to monitor your liver function while you are using this medication.

If you experience symptoms of liver problems (e.g., yellowing of the skin or eyes, abdominal pain, loss of appetite, dark urine, pale stools, nausea, or vomiting), contact your doctor immediately.

Migraine headaches: If you have migraines with aura (headache is associated with symptoms such as flashes of light, tingling sensations, blind spots, muscle weakness, or difficulty speaking either before or during the headache), you should not use this medication.

If you have migraine without aura, estrogen can aggravate your migraines. Talk to your doctor if you notice any change in your migraine pattern while taking estrogen.

Ovarian cancer: There are studies that have found the use of hormone replacement therapy for longer than 5 years is associated with an increased risk cancer of the ovaries. If you have or have had ovarian cancer, you should not use this medication.

Seizures: Estrogens may increase your risk of having a seizure. If you have a seizure disorder or a history of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Thyroid disease: Estrogen may affect how thyroid hormone is used by the body. If you are taking thyroid medication to supplement an underactive thyroid gland, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Pregnancy: This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor.

Breast-feeding: Estrogen and progestin pass into breast milk. Those who are breast-feeding should not use this medication.

Children: The safety and effectiveness of using this medication have not been established for children.

There may be an interaction between estradiol–norethindrone patches and any of the following:

• anastrozole
• apalutamide
• aprepitant
• "azole" antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• bosentan
• carbamazepine
• celecoxib
• clarithromycin
• cobicistat
• corticosteroids (e.g., dexamethasone, prednisone)
• diabetes medication (e.g., acarbose, canagliflozin, gliclazide, insulin, lixisenatide, metformin, rosiglitazone)
• elagolix
• enzalutamide
• eslicarbazepine
• heparin
• HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine)
• HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir)
• hyaluronidase
• lamotrigine
• lenalidomide
• lumacaftor and ivacaftor
• melatonin
• mifepristone
• modafinil
• muscle relaxants (e.g., dantrolene, tizanidine)
• nirmatrelvir
• ospemifene
• phenobarbital
• phenytoin
• primidone
• progesterone
• rifabutin
• rifampin
• ropinirole
• St. John's wort
• somatropin
• tacrolimus
• thalidomide
• theophyllines (e.g., aminophylline, theophylline)
• tranexamic acid
• thyroid medications (e.g., thyroid, levothyroxine)
• tyrosine kinase inhibitors (e.g., dabrafenib, idelalisib, tucatinib)
• ulipristal
• ursodiol

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.