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Relugolix, estradiol, and norethindrone (Oral)

Medically reviewed by Drugs.com. Last updated on Oct 17, 2022.

Oral route(Tablet)

Estrogen and progestin combination products, including relugolix/estradiol/norethindrone acetate, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI), especially in women at increased risk for these events. Relugolix/estradiol/norethindrone acetate is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension .

Commonly used brand name(s)

In the U.S.

  • Myfembree

Available Dosage Forms:

  • Tablet

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Luteinizing Hormone Releasing Hormone Antagonist

Uses for relugolix, estradiol, and norethindrone

Relugolix, estradiol, and norethindrone combination is used to manage heavy menstrual bleeding caused by uterine leiomyomas (fibroids) in premenopausal women. It is also used to manage moderate to severe pain caused by endometriosis in premenopausal women.

Relugolix, estradiol, and norethindrone is available only with your doctor's prescription.

Before using relugolix, estradiol, and norethindrone

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For relugolix, estradiol, and norethindrone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to relugolix, estradiol, and norethindrone or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of relugolix, estradiol, and norethindrone combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of relugolix, estradiol, and norethindrone combination in geriatric patients.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking relugolix, estradiol, and norethindrone, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using relugolix, estradiol, and norethindrone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Tranexamic Acid

Using relugolix, estradiol, and norethindrone with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Abametapir
  • Amifampridine
  • Amiodarone
  • Amoxicillin
  • Ampicillin
  • Amprenavir
  • Apalutamide
  • Aprepitant
  • Armodafinil
  • Artemether
  • Bacampicillin
  • Belzutifan
  • Betamethasone
  • Bexarotene
  • Bosentan
  • Bupropion
  • Carbamazepine
  • Carbenicillin
  • Carvedilol
  • Cefaclor
  • Cefadroxil
  • Cefdinir
  • Cefditoren
  • Cefixime
  • Cefpodoxime
  • Cefprozil
  • Ceftazidime
  • Ceftibuten
  • Cefuroxime
  • Cenobamate
  • Ceritinib
  • Clarithromycin
  • Clavulanic Acid
  • Clobazam
  • Cloxacillin
  • Cobicistat
  • Colesevelam
  • Conivaptan
  • Cyclacillin
  • Cyclosporine
  • Dabrafenib
  • Darunavir
  • Dexamethasone
  • Dicloxacillin
  • Donepezil
  • Doxycycline
  • Dronedarone
  • Efavirenz
  • Elagolix
  • Elvitegravir
  • Encorafenib
  • Enzalutamide
  • Erythromycin
  • Eslicarbazepine Acetate
  • Etravirine
  • Fedratinib
  • Fexinidazole
  • Flibanserin
  • Fosamprenavir
  • Fosaprepitant
  • Fosnetupitant
  • Fosphenytoin
  • Griseofulvin
  • Guar Gum
  • Isotretinoin
  • Itraconazole
  • Ivosidenib
  • Ketoconazole
  • Lapatinib
  • Lesinurad
  • Lixisenatide
  • Lorlatinib
  • Lumacaftor
  • Mavacamten
  • Minocycline
  • Mitapivat
  • Mitotane
  • Mobocertinib
  • Modafinil
  • Mycophenolate Mofetil
  • Mycophenolic Acid
  • Nafcillin
  • Nelfinavir
  • Netupitant
  • Nevirapine
  • Octreotide
  • Oxacillin
  • Oxcarbazepine
  • Oxytetracycline
  • Penicillin G
  • Penicillin G Procaine
  • Penicillin V
  • Phenobarbital
  • Phenylbutazone
  • Phenytoin
  • Pitolisant
  • Pixantrone
  • Prednisone
  • Primidone
  • Quinidine
  • Ranolazine
  • Red Clover
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Rufinamide
  • Secobarbital
  • St John's Wort
  • Sugammadex
  • Sultamicillin
  • Tazemetostat
  • Telaprevir
  • Tetracycline
  • Theophylline
  • Ticarcillin
  • Tigecycline
  • Tirzepatide
  • Tizanidine
  • Topiramate
  • Troglitazone
  • Ulipristal
  • Valproic Acid
  • Vemurafenib
  • Verapamil

Using relugolix, estradiol, and norethindrone with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Amitriptyline
  • Atazanavir
  • Clomipramine
  • Diazepam
  • Doxepin
  • Ginseng
  • Imipramine
  • Lamotrigine
  • Levothyroxine
  • Licorice
  • Lorazepam
  • Parecoxib
  • Prednisolone
  • Selegiline
  • Tacrine
  • Temazepam
  • Tipranavir
  • Triazolam
  • Troleandomycin
  • Valdecoxib
  • Voriconazole
  • Warfarin

Interactions with food/tobacco/alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using relugolix, estradiol, and norethindrone with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use relugolix, estradiol, and norethindrone, or give you special instructions about the use of food, alcohol, or tobacco.

  • Caffeine

Other medical problems

The presence of other medical problems may affect the use of relugolix, estradiol, and norethindrone. Make sure you tell your doctor if you have any other medical problems, especially:

  • Abnormal or unusual vaginal bleeding or
  • Blood clots (eg, deep vein thrombosis, pulmonary embolism) or history of or
  • Breast cancer or history of or
  • Heart attack, history of or
  • Heart or blood vessel disease or
  • Heart rhythm problems (eg, atrial fibrillation) or
  • Hypertension (high blood pressure), uncontrolled or
  • Liver disease, severe or
  • Migraine headache or
  • Osteoporosis (weak bones) or
  • Stroke, history of—Should not be used in patients with these conditions.
  • Cholestatic jaundice (bile problem) during pregnancy or previous pill use (eg, estrogen), history of or
  • Diabetes or
  • Dyslipidemia (high cholesterol in the blood) or
  • Fracture (broken bone), history of or
  • Gallbladder disease or
  • Mental problems (eg, depression) or history—Use with caution. May make these conditions worse.
  • Obesity—Use with caution. May increase risk for more side effects.

Proper use of relugolix, estradiol, and norethindrone

Take relugolix, estradiol, and norethindrone only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Relugolix, estradiol, and norethindrone comes with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Take the tablet at about the same time each day, with or without food.

Use relugolix, estradiol, and norethindrone within 7 days from the start of your menstrual period.

You may receive other medicines (eg, calcium or vitamin D supplements) to help reduce bone loss.

Take relugolix, estradiol, and norethindrone at least 6 hours before taking other medicines called P-gp inhibitors. Ask your doctor about these medicines.

Dosing

The dose of relugolix, estradiol, and norethindrone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of relugolix, estradiol, and norethindrone. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablet):
    • For heavy menstrual bleeding caused by uterine fibroids and moderate to severe pain caused by endometriosis:
      • Adults—One tablet once a day for up to 24 months. Each tablet contains 40 milligrams (mg) relugolix, 1 mg estradiol, and 0.5 mg norethindrone.
      • Children—Use and dose must be determined.

Missed dose

If you miss a dose of relugolix, estradiol, and norethindrone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions while using relugolix, estradiol, and norethindrone

It is very important that your doctor check your progress at regular visits to make sure relugolix, estradiol, and norethindrone is working properly. Blood and urine tests may be needed to check for unwanted effects.

Relugolix, estradiol, and norethindrone may increase your risk of early pregnancy loss. Your doctor may give you a pregnancy test before you start using relugolix, estradiol, and norethindrone to make sure you are not pregnant. Birth control pills may not work as well to prevent pregnancy when used with relugolix, estradiol, and norethindrone. Use another form of birth control (eg, condoms, spermicide) during treatment and for at least 1 week after the last dose. If a pregnancy occurs while using the medicine, tell your doctor right away.

Do not use relugolix, estradiol, and norethindrone if you smoke cigarettes or if you are over 35 years old. If you smoke while using relugolix, estradiol, and norethindrone, you increase your risk of having a heart attack, stroke, or blood clot. Your risk is even higher if you are over age 35, if you have diabetes, high blood pressure, high cholesterol, or if you are overweight. Talk with your doctor about ways to stop smoking. Keep your diabetes under control. Ask your doctor about diet and exercise to control your weight and blood cholesterol level.

Check with your doctor right away if you have pain in the chest, groin, or legs, especially the calves, difficulty with breathing, a sudden, severe headache, slurred speech, a sudden, a sudden loss of coordination, or vision changes while using relugolix, estradiol, and norethindrone.

Relugolix, estradiol, and norethindrone can cause your bone mineral density to decrease, which may lead to osteoporosis or weakened bones. Check with your doctor if you have pain in the back, ribs, arms, or legs, or a decrease in your height.

Relugolix, estradiol, and norethindrone may increase your risk of having hormone-sensitive cancer, including breast cancer. Check with your doctor right away if you have clear or bloody discharge from the nipple, an inverted nipple, dimpling of the breast skin, a lump in the breast or under the arm, crusting or scaling of the nipple, redness or swelling of the breast, or a sore on the skin of the breast that does not heal.

Relugolix, estradiol, and norethindrone may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Also tell your doctor if you have sudden or strong feelings, including feeling nervous, angry, restless, violent, or scared. If you or your caregiver notice any of these side effects, tell your doctor right away.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea or vomiting, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver or gallbladder problem.

Relugolix, estradiol, and norethindrone may cause changes in menstrual bleeding, which may decrease your ability to recognize pregnancy. Talk to your doctor if you have concerns.

Relugolix, estradiol, and norethindrone may cause thinning or loss of hair. Talk with your doctor if you have any concerns about this.

Make sure any doctor or dentist who treats you knows that you are using relugolix, estradiol, and norethindrone. You may need to stop using relugolix, estradiol, and norethindrone for at least 4 to 6 weeks before having surgery.

Before you have any medical tests, tell the medical doctor in charge that you are taking relugolix, estradiol, and norethindrone. The results of some tests may be affected by relugolix, estradiol, and norethindrone.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Relugolix, estradiol, and norethindrone side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  • Heavy non-menstrual vaginal bleeding
  • longer or heavier menstrual periods
  • normal menstrual bleeding occurring earlier, possibly lasting longer than expected
  • unusually heavy or unexpected menstrual bleeding
  • vaginal bleeding or spotting

Less common

  • Anxiety
  • discouragement
  • feeling sad or empty
  • hair loss, thinning of hair
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • mood swings
  • trouble concentrating
  • trouble sleeping
  • unusual tiredness or weakness

Rare

  • Pelvic pain
  • stomach pain, bloating

Incidence not known

  • Blurred vision
  • chest pain or tightness
  • chills
  • clay-colored stools
  • cough
  • dark urine
  • diarrhea
  • dizziness or lightheadedness
  • dry mouth
  • fainting
  • fast heartbeat
  • fever
  • fruit-like breath odor
  • headache
  • hives, itching
  • increased hunger
  • increased thirst
  • increased urination
  • loss of appetite
  • loss of consciousness
  • nausea and vomiting
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • skin rash
  • trouble breathing
  • unexplained weight loss
  • unpleasant breath odor
  • vomiting of blood
  • yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Feeling of warmth
  • increased sweating
  • night sweats
  • redness of the face, neck, arms, and occasionally, upper chest
  • toothache

Less common

  • Back pain
  • decreased interest in sexual intercourse
  • difficulty in moving
  • inability to have or keep an erection
  • joint pain
  • loss in sexual ability, desire, drive, or performance
  • muscle pain or stiffness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Further information

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