Elagolix, Estradiol, and Norethindrone

The combination of elagolix, estradiol, and norethindrone is used to treat heavy menstrual bleeding caused by uterine fibroids (growths in the uterus that are not cancer). Elagolix 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. Elagolix 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.

The combination of elagolix, estradiol, and norethindrone comes as capsules to take by mouth. It is usually taken with or without food twice daily for up to 24 months. This medication comes in a package that contains 28 days of medication. Each weekly dose package has two different types of capsules, 7 containing the combination of elagolix, estradiol, and norethindrone (yellow and white capsules) and 7 containing elagolix (blue and white capsules). Take elagolix, estradiol, and norethindrone (1 capsule) every morning and then take elagolix (1 capsule) every evening. Take elagolix, estradiol, and norethindrone at around the same time(s) 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 elagolix, estradiol, and norethindrone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

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.

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

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

• tell your doctor and pharmacist if you are allergic to elagolix, estradiol, norethindrone, aspirin, tartrazine (a yellow dye found in some medications), any other medications, or any of the ingredients in elagolix, estradiol, and norethindrone capsules. Ask your pharmacist or check the Medication Guide for a list of the ingredients.

• tell your doctor if you are taking cyclosporine (Gengraf, Neoral, Sandimmune) or gemfibrozil (Lopid). Your doctor may probably tell you not to take the combination of elagolix, estradiol, and norethindrone if you are taking one or more of these medications.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: digoxin (Lanoxin); ketoconazole; levothyroxine (Levoxyl, Synthroid, Tirosint, others); midazolam (Nayzilam); phenytoin (Dilantin, Phenytek); proton pump inhibitors such as dexlansoprazole (Dexilant), esomeprazole (Nexium, in Vimovo), lansoprazole (Prevacid), omeprazole (Prilosec, in Talicia, in Yosprala, in Zegred), pantoprazole (Protonix), and rabeprazole (Aciphex); rifampin (Rifadin, in Rifamate, in Rifater); rosuvastatin (Crestor); and steroids such as dexamethasone (Hemady), methylprednisolone (Medrol), prednisone, and prednisolone (Orapred ODT, Pediapred, Prelone ). Also, tell your doctor or pharmacist if you are taking vitamin or mineral supplements that contain iron. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with elagolix, estradiol, and norethindrone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• 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 elagolix, 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 elagolix, 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 within 7 days after you start your menstrual period to be sure that you are not pregnant when you taking elagolix, estradiol, and norethindrone. Elagolix, estradiol, and norethindrone may interfere with the action of certain hormonal contraceptives, so you should not use these as your only method of 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 elagolix, estradiol, and norethindrone, call your doctor immediately. Elagolix, estradiol, and norethindrone may harm 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 elagolix, 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.

Do not eat grapefruit or drink grapefruit juice while taking this medication.

Take the missed dose as soon as you remember it. However, if it is more than 4 hours since your last dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

• Elagolix, 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)

  • changes in menstrual periods (irregular bleeding or spotting, little or no bleeding, decreased length of periods)

  • headache

  • weight gain

  • joint pain

  • changes in sexual desire

  • drowsiness or tiredness

• 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:

  • yellowing of the skin or eyes

  • unusual bruising or bleeding

  • loss of appetite

  • extreme tiredness, weakness, or lack of energy

  • 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 elagolix, 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.

• Elagolix, 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 (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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. http://www.upandaway.org

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 (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. 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

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

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

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.

• Norethisterone