How does this medication work? What will it do for me?

This medication contains two medications: an estrogen (estradiol-17β) and a progestin (levonorgestrel). It belongs to the class of medications known as hormone replacement therapy.

This medication is used to treat menopausal symptoms such as hot flushes, sweating, and chills. When an estradiol-17β - levonorgestrel patch is applied to your skin, it releases the hormones into your blood through your skin.

Estrogens and progestins 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 sweating can occur. Most women reach menopause naturally around the age of 50, but some women may experience menopause sooner due to many causes, including surgery.

This medication is designed for women who have not had a hysterectomy (removal of the uterus or womb). These women require progestin while taking estrogen to prevent complications associated with taking estrogen alone, such as the overgrowth of the uterine lining (endometrial hyperplasia).

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 being given this medication, speak to your doctor. Do not stop using 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 use this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Each translucent system contains estradiol hemihydrate 4.55 mg (equivalent to 4.40 mg of estradiol-17β) and levonorgestrel 1.39 mg and provides controlled delivery of estradiol-17β 45 µg/day and levonorgestrel 15 µg/day. Nonmedicinal ingredients: acrylate copolymer adhesive and polyvinylpyrrolidone/vinyl acetate copolymer.

How should I use this medication?

One 28-day treatment cycle with this medication consists of 4 patches. Each patch provides 45 µg of estradiol-17β per day plus 15 µg of levonorgestrel per day.

A new patch should be applied to your skin on the same day once a week (change the patch every 7 days). Once the 28-day period has been completed, the next cycle starts again with a fresh package of patches.

Many things can affect the dose of a 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 applying the medication without consulting your doctor.

To apply the patch:

  1. Choose a clean, dry area of intact skin that is not oily, damaged or irritated, or exposed to the sun.
  2. Tear open the pouch containing the patch rather than using scissors – if you accidentally cut the patch, it will be useless.
  3. Remove the protective layer. Apply the patch to the selected area immediately. Avoid touching the adhesive.
  4. 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.

Apply the patch to the lower back or abdomen, buttocks, or hip. Many women have found that less skin irritation occurs when the patch is applied to the 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).

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. Once the patch has been applied, it should not be exposed to the sun for prolonged periods of time.

When changing the patch, remove the old one carefully, folding the adhesive side inwards, and throw it away or bring it to the pharmacy for proper disposal. Keep it out of the reach of children or pets, as there is still active medication in the patch. If adhesive remains on your skin, rub it off gently.

It is important to use this medication exactly as prescribed by your doctor. If you forget to apply or change your patch, change it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not wear two patches at once. If you are not sure what to do after forgetting to apply or change your patch, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children. Do not refrigerate or freeze. Do not store the patches out of the pouch.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not use this medication if you:

  • are allergic to estradiol-17β, levonorgestrel, or any ingredients of this medication
  • are or may be pregnant
  • are breast-feeding
  • experience classic migraines
  • have active liver disease, especially obstructive liver disease
  • have endometrial hyperplasia (thickening of the inner lining of the uterus)
  • have or have had an estrogen-dependent type of cancer such as breast or endometrial cancer
  • have or have had blood clots (such as deep vein thrombosis or a pulmonary embolism) or active thrombophlebitis (inflammation of the legs)
  • have or have had stroke, heart attack, or coronary heart disease
  • have partial or complete loss of vision from blood vessel disease of the eyes
  • have unusual vaginal bleeding that has not been checked by a doctor

What side effects are possible with this medication?

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 uses 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 using 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.

  • acne
  • appetite changes
  • bloating or gas
  • breast tenderness and excess vaginal secretions
  • changes in menstrual flow
  • depression
  • discomfort wearing contact lenses
  • dizziness
  • fluid retention
  • general feeling of tiredness
  • headache
  • increased body hair
  • irritability
  • menstrual pain
  • migraine headaches
  • muscle aches
  • nausea or vomiting
  • redness, itching, spots, burning, and swelling underneath or around the area of the skin on which the patch is applied
  • vaginal itching with or without discharge
  • weight gain or loss

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 enlargement or lumps
  • changes in speech
  • changes in vision
  • darkened skin (chloasma) around areas where the patch is applied
  • dizziness and faintness
  • fluid retention
  • intolerable breast tenderness
  • irregular or unusual vaginal bleeding
  • mood swings
  • persistent or severe skin irritation
  • persistent upper abdominal pain, nausea, vomiting, or a tender abdomen (stomach)
  • severe headaches
  • upper abdominal pain or swelling
  • yellowing of eyes or skin (signs of jaundice)

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

  • first migraine headache
  • rapid pulse or dizziness
  • signs of a serious allergic reaction (i.e., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • signs of blood clot formation (e.g., coughing blood, pains in chest, groin or leg, especially in calf of leg, weakness or numbness in arm or leg)
  • signs of heart attack (e.g., chest pain, tightness, sweating, nausea)
  • signs of stroke (e.g., sudden or severe headache, sudden loss of coordination, sudden and unexplained shortness of breath, sudden slurring of speech, sudden vision changes)
  • tender or painful inflammation of the veins

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.

Are there any other precautions or warnings for 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.

Note the following important information about estrogen replacement therapy:

The Women's Health Initiative (WHI) study results indicated an increased risk of heart attack, stroke, breast cancer, blood clots in the lungs, and blood clots in the leg veins in postmenopausal women during 5 years of treatment with 0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone compared to women receiving sugar tablets. Other combinations of estrogen and progestins were not studied. However, until additional data are available, the risks should be assumed to be similar for other hormone replacement products. Therefore,

  • estrogens with or without progestins should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible, as directed by your doctor; and
  • estrogens with or without progestins should not be used to prevent heart disease, heart attacks, or strokes.

Allergy: Contact allergy, such as itching and redness, is known to occur with the application of estrogen to the skin. Although this allergy is extremely rare, people who develop skin reactions or contact sensitization to any component of the medication are at risk of developing a severe allergic reaction with continued use. If you have a skin reaction to the patch, contact your doctor for advice.

Blood clotting disorders: Estrogens with or without progestins are associated with an increased risk of blood clots in the lungs (pulmonary embolism) and legs (deep vein thrombosis). This risk also increases with age, a personal or family history of blood clots, smoking, and obesity. The risk of blood clots is also increased if you are immobilized for prolonged periods and with 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: Women may experience increased blood pressure when using hormone replacement therapy. Your doctor may want to monitor your blood pressure more frequently while you are using estradiol-17β - levonorgestrel, especially if high doses of estrogen are used. Ask your doctor how often you should have your blood pressure checked.

Bone disease: If you have bone disease due to cancer or a metabolic condition causing too much calcium in your body, 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 and ovarian cancer: Studies indicate an increased risk of breast and ovarian cancer with long-term use of estrogen replacement therapy. Do not use estrogens if you have a history of breast cancer. Your doctor will monitor your condition closely if you have breast nodules, fibrocystic disease, an abnormal mammogram, or a strong family history of breast cancer. While taking estrogens, have regular breast examinations and become familiar with your breasts so you can let your doctor know if anything has changed. Do not apply the estradiol-17β - levonorgestrel patch to your breasts, as it may have harmful effects on the breast tissue.

Dementia: Women 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 whether you should be tested for dementia.

Diabetes: If you have diabetes, your doctor should closely monitor your condition while you are using this medication, as it may affect blood sugar control.

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

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 levonorgestrel (progestin) in this medication should counteract the risk of endometrial cancer.

Endometriosis: Estrogen replacement therapy can cause endometriosis to reappear or get worse. If you have or have had endometriosis, 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.

Fluid retention: Estrogen may cause fluid retention, which can worsen some medical conditions (e.g., heart disease, kidney disease, epilepsy, asthma). Talk to your doctor if you have any concerns.

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. Get immediate medical attention 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).

High cholesterol or triglycerides: Estrogen may increase triglyceride levels in those who already have high levels. Your doctor will monitor your cholesterol and triglyceride levels while you are taking this medication.

Kidney disease: Estrogen can affect how calcium and phosphorus are metabolized by your body. If you have kidney 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.

Liver disease: People with active liver disease or liver tumours should not use estradiol-17β - levonorgestrel patches. 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 estradiol-17β - levonorgestrel patches.

Other medical conditions: Women with epilepsy, migraine headaches, or asthma should discuss with their doctor how this medication may affect their medical condition, how their medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

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

Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are using estradiol-17β - levonorgestrel, it may affect your baby. This medication is not recommended for breast-feeding women.

Children: The safety and effectiveness of using this medication have not been established for children. This medication is not intended for use by children.

What other drugs could interact with this medication?

There may be an interaction between estradiol-17β - levonorgestrel patches and any of the following medications:

  • acetaminophen
  • acitretin
  • alcohol
  • amiodarone
  • anastrozole
  • antidiabetes medication (e.g., insulin, metformin, glyburide)
  • aprepitant
  • ascorbic acid (vitamin C)
  • atorvastatin
  • "azole" antifungals (e.g., ketoconazole, fluconazole, itraconazole)
  • barbiturates (e.g., butalbital, phenobarbital)
  • bosentan
  • carvedilol
  • celecoxib
  • cholestyramine
  • cobicistat
  • corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
  • cyclosporine
  • cyproterone
  • dipyridamole
  • doxorubicin
  • dronedarone
  • efavirenz
  • etravirine
  • grapefruit juice
  • heparin
  • low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
  • macrolide antibiotics (e.g., clarithromycin, erythromycin)
  • medications used to treat high blood pressure (e.g., atenolol, rampiril, enalapril, lisinopril, amlodipine)
  • mefloquine
  • meprobamate
  • mitotane
  • modafinil
  • morphine
  • mycophenolate
  • nefazodone
  • perampanel
  • prazosin
  • progesterone
  • propranolol
  • prucalopride
  • retinoic acid medications (e.g., etretinate, isotretinoin)
  • quinidine
  • quinine
  • rifampin
  • ritonavir
  • St. John's wort
  • salicylic acid
  • seizure medications (e.g., carbamazepine, phenobarbital, phenytoin, primidone, topiramate)
  • tacrolimus
  • tamoxifen
  • telaprevir
  • temazepam
  • theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
  • tranexamic acid
  • trazodone
  • tyrosine kinase inhibitors (e.g., dabrafenib, imatinib, nilotinib, sunitinib)
  • vinblastine
  • warfarin

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.