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Estradiol and norethindrone (transdermal)

Generic name: estradiol and norethindrone (transdermal) [ ES-tra-DYE-ol-and-nor-ETH-in-drone ]
Brand name: Combipatch
Dosage form: transdermal film, extended release (0.05 mg-0.14 mg/24 hours; 0.05 mg-0.25 mg/24 hours)
Drug class: Sex hormone combinations

Medically reviewed by on Oct 5, 2022. Written by Cerner Multum.

What are estradiol and norethindrone?

Estradiol and norethindrone transdermal (skin patch) is a combination medicine used to treat menopause symptoms such as hot flashes and vaginal changes. estradiol and norethindrone is also used before menopause to treat a lack of estrogen caused by conditions such as hypogonadism, primary ovarian failure, or surgical removal of the ovaries.

Estradiol and norethindrone may also be used for purposes not listed in this medication guide.


Using this medicine can increase your risk of blood clots, stroke, heart attack, or cancer of the breast, uterus, or ovaries. Estradiol and norethindrone should not be used to prevent heart disease, stroke, or dementia.

Before taking this medicine

You should not use estradiol and norethindrone if you are allergic to estradiol or norethindrone, or if you have:

Do not use estradiol and norethindrone if you have had your uterus (womb) removed.

Do not use estradiol and norethindrone if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Using this medicine can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, if you are overweight, or if you smoke.

Estradiol and norethindrone should not be used to prevent heart disease, stroke, or dementia, because this medicine may actually increase your risk of developing these conditions.

Tell your doctor if you have ever had:

  • heart disease;

  • liver problems;

  • kidney disease;

  • angioedema (swelling of face and tongue);

  • lupus;

  • asthma;

  • diabetes;

  • epilepsy or other seizure disorder;

  • migraines;

  • porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

  • gallbladder disease;

  • endometriosis;

  • high levels of calcium levels in your blood;

  • a thyroid disorder; or

  • if you have any unusual vaginal bleeding.

Using estradiol and norethindrone may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk.

Ask a doctor if it is safe to breastfeed while using this medicine.

How should I use estradiol and norethindrone?

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

If you need major surgery or will be on long-term bed rest, you may need to stop using this medicine for a short time. Any doctor who treats you should know that you are using estradiol and norethindrone.

Your doctor should check your progress on a regular basis to determine whether you should continue this treatment. Self-examine your breasts for lumps on a monthly basis, and have regular mammograms while using estradiol and norethindrone.

Store estradiol and norethindrone in the refrigerator in the foil pouch, do not freeze. Take the medicine out of the refrigerator and let it reach room temperature before application.

What happens if I miss a dose?

Apply the next patch as soon as you remember, and follow your regular schedule for changing the patch. Do not apply two patches at one time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while using estradiol and norethindrone?

Avoid smoking. It can greatly increase your risk of blood clots, stroke, or heart attack while using estradiol and norethindrone.

Grapefruit may interact with estradiol and lead to unwanted side effects. Avoid the use of grapefruit products.

Avoid using creams, lotions, or powders on the skin where you apply the patch, or it may not stick to your skin.

Estradiol and norethindrone side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Remove the skin patch and call your doctor at once if you have:

  • heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

  • increased blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nosebleed;

  • signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

  • signs of a blood clot--sudden vision loss, stabbing chest pain, feeling short of breath, coughing up blood, pain or warmth in one or both legs;

  • swelling or tenderness in your stomach;

  • jaundice (yellowing of the skin or eyes);

  • unusual vaginal bleeding, pelvic pain;

  • a breast lump;

  • memory problems, confusion, unusual behavior; or

  • high levels of calcium in your blood--nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, lack of energy.

Common side effects of estradiol and norethindrone may include:

  • nausea, vomiting, stomach cramps;

  • bloating, swelling, weight gain;

  • breast pain;

  • light vaginal bleeding or spotting;

  • vaginal itching or discharge;

  • headache;

  • thinning scalp hair; or

  • redness or irritation where the patch is worn.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect estradiol and norethindrone?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may affect estradiol and norethindrone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.