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Relugolix, Estradiol, and Norethindrone

pronounced as (rel" ue goe' lix)


Medications containing estradiol and norethindrone may increase the risk of heart attack, stroke, and blood clots in the lungs and legs. Tell your doctor if you smoke and if you have or have ever had a heart attack; a stroke; blood clots in your legs, lungs or eyes; heart valve disease; fast or irregular heartbeat; thrombophilia (condition in which the blood clots easily); migraine headaches; high blood pressure; high blood levels of cholesterol or fats; or diabetes that has affected your circulation. Your doctor may tell you that you should not take this medication if you have or have had any of these conditions. If you are having surgery or will be on bedrest, your doctor may want you to stop taking this medication at least 4 to 6 weeks before the surgery or bedrest.

If you experience any of the following side effects, call your doctor immediately: sudden, severe headache; sudden partial or complete loss of vision; double vision; speech problems; dizziness or faintness; weakness or numbness of an arm or a leg; crushing chest pain or chest heaviness; coughing up blood; sudden shortness of breath; or pain, tenderness, or redness in one leg.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with relugolix, estradiol, and norethindrone and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( or the manufacturer's website to obtain the Medication Guide.

Talk to your doctor about the risk(s) of taking relugolix, estradiol, and norethindrone.

Why is this medication prescribed?

The combination of relugolix, estradiol, and norethindrone is used to treat heavy menstrual bleeding caused by uterine fibroids (growths in the uterus that are not cancer). It is also used to manage pain due to endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body and causes infertility). Relugolix is in a class of medications called gonadotropin-releasing hormone (GnRH) receptor antagonists. Estradiol is in a class of medications called estrogen hormones. Norethindrone is in a class of medications called progestins. Relugolix works by decreasing the amount of certain hormones in the body. Estradiol works by replacing estrogen that is normally produced by the body. Norethindrone works by stopping the lining of the uterus from growing and by causing the uterus to produce certain hormones.

How should this medicine be used?

The combination of relugolix, estradiol, and norethindrone comes as a tablet to take by mouth. It is usually taken with or without food once a day for up to 24 months. Take relugolix, estradiol, and norethindrone at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take relugolix, estradiol, and norethindrone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you are just starting to take the combination of relugolix, estradiol, and norethindrone, you should begin your treatment within 7 days after you start your menstrual period. If you start relugolix, estradiol, and norethindrone on another day, your period may be heavy or irregular for the first month after starting treatment.

Your doctor may prescribe or recommend a calcium and vitamin D supplement to take during your treatment. You should take these supplements as directed by your doctor.

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking the combination of relugolix, estradiol, and norethindrone,

  • tell your doctor and pharmacist if you are allergic to relugolix, estradiol, norethindrone, any other medications, or any of the ingredients in relugolix, estradiol, and norethindrone tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had breast cancer; cancer of the cervix, vagina, or lining of the uterus; osteoporosis (condition where bones are thin and more likely to break); unexplained abnormal vaginal bleeding; peripheral vascular disease (poor circulation in the blood vessels); heart or liver disease or any other type of liver problems. Your doctor may probably tell you not to take the combination of relugolix, estradiol, and norethindrone.
  • tell your doctor if you have or have ever had ever had broken bones; depression, anxiety, unusual changes in behavior or mood, or thoughts about or attempted suicide; gall bladder disease; jaundice (yellowing of the skin or eyes); thyroid problems; or adrenal insufficiency (condition in which the adrenal glands do not produce enough of certain hormones needed for important body functions).
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. Do not take relugolix, estradiol, and norethindrone if you are pregnant or think you are pregnant. Your doctor will perform a pregnancy test prior to starting treatment or tell you to begin your treatment to be sure that you are not pregnant when you begin taking relugolix, estradiol, and norethindrone. Relugolix, estradiol, and norethindrone may interfere with the action of certain hormonal contraceptives and increase side effects, so you should not use these as birth control during your treatment. You will need to use a reliable non-hormonal method of birth control to prevent pregnancy during your treatment and for 1 week after your final dose. Ask your doctor to help you choose a method of birth control that will work for you. If you become pregnant while taking relugolix, estradiol, and norethindrone, call your doctor immediately. Relugolix, estradiol, and norethindrone may cause early pregnancy loss and/or harm to the fetus.
  • you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking relugolix, estradiol, and norethindrone. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: new or worsening irritability, anxiety, or depression; talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can this medication cause?

Relugolix, estradiol, and norethindrone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • hair loss or hair thinning
  • hot flashes (a sudden wave of mild or intense body heat)
  • increased sweating or night sweats
  • changes in menstrual periods (irregular bleeding or spotting, little or no bleeding, decreased length of periods)
  • hair loss or hair thinning
  • headache
  • decreased sexual desire
  • drowsiness or tiredness
  • toothache
  • joint or back pain

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

  • swelling of the face, lips, mouth or tongue; trouble breathing; rash; red or swollen skin
  • yellowing of the skin or eyes
  • unusual bruising or bleeding
  • loss of appetite
  • dark-colored urine
  • light-colored stool
  • pain in the upper right part of stomach
  • nausea
  • vomiting
  • swelling of the hands, feet, or lower legs

The combination of relugolix, estradiol, and norethindrone may cause or worsen osteoporosis. It can decrease the density of your bones and increase the chance of broken bones and fractures. Talk to your doctor about the risks of taking this medication.

Relugolix, estradiol, and norethindrone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online ( or by phone (1-800-332-1088).

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( for more information if you do not have access to a take-back program.

In case of emergency/overdose

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Symptoms of overdose may include:

  • nausea
  • vomiting
  • breast tenderness
  • abdominal pain
  • drowsiness or tiredness
  • vaginal bleeding

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to relugolix, estradiol, and norethindrone.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Brand names

  • Myfembree®

Other names

  • Norethisterone
Last Revised - 10/15/2022