Mifepristone

Included as part of the PRECAUTIONS section.

Mifepristone is a prescription medicine used to treat high blood sugar caused by high cortisol levels in the blood in adults with Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.

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

Do not take mifepristone if you are taking:

• simvastatin (Zocor, Vytorin, Juvisync, Simcor)
• lovastatin (Mevacor, Altoprev, Advicor)
• cyclosporine (Gengraf, Neoral, Restasis, Sandimmune)
• dihydroergotamine (Migranal)
• ergotamine (Ergomar, Migerot)
• fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Onsolis, Sublimaze Preservative Free, Sunsys)
• pimozide (Orap)
• quinidine (Neudexta)
• sirolimus (Rapamune, Torisel)
• tacrolimus (Prograf, Protopic)

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins,  and herbal supplements. Especially tell your doctor if you take:

• cortisone
• dexamethasone
• methylprednisolone
• prednisolone
• prednisone
• warfarin (Coumadin, Jantoven)

This is not a complete list of mifepristone drug interactions. Ask your doctor or pharmacist for more information.

Do not take mifepristone during pregnancy. See "Black Box Warning".

Mifepristone can cause serious side effects, including:

• Loss of a pregnancy. Women who can become pregnant must:
  • have a negative pregnancy test before starting mifepristone
  • have a negative pregnancy test before restarting mifepristone if you stop taking it for more than 14 days
  • use a non-hormonal form of birth control while taking mifepristone and for 1 month after stopping mifepristone. Talk to your doctor about how to prevent pregnancy. Tell your doctor right away if you think you may be pregnant.

• Take mifepristone exactly as your doctor tells you.
• Your doctor may change your dose if needed.
• Mifepristone is usually taken 1 time each day.
• Take mifepristone with food.
• Swallow mifepristone whole. Do not split, crush or chew mifepristone tablets. If you cannot swallow mifepristone tablets whole, tell your doctor.

You should not take Korlym if you are allergic to mifepristone, or if you have:

• endometrial hyperplasia or a certain type of uterine cancer;

• unusual or unexplained vaginal bleeding;

• if you are pregnant; or

• if you take steroid medications because of a serious illness or condition (such as an organ transplant).

The following drugs should not be used while you are taking Korlym:

• cyclosporine (Gengraf, Neoral, Restasis, Sandimmune);

• dihydroergotamine (Migranal) or ergotamine (Ergomar, Migergot);

• fentanyl (Abstral, Actiq, Fentora, Duragesic, Lazanda, Onsolis, Sublimaze, Subsys);

• pimozide (Orap);

• quinidine (Neudexta);

• lovastatin (Mevacor, Altoprev, Advicor) or simvastatin (Zocor, Simcor, Vytorin, Juvisync); or

• sirolimus (Rapamune, Torisel) or tacrolimus (Prograf, Protopic).

To make sure Korlym is safe for you, tell your doctor if you have ever had:

• low levels of potassium in your blood;

• heart disease;

• a bleeding or blood-clotting disorder, or if you take a blood thinner such as warfarin (Coumadin, Jantoven);

• liver or kidney disease;

• an organ transplant; or

• a problem with your thyroid or adrenal glands.

Mifepristone can harm an unborn baby or cause a miscarriage. Do not use if you are pregnant. Stop taking Korlym and tell your doctor right away if you become pregnant during treatment.

You will need to have a negative pregnancy test before you start taking Korlym, or if you restart the medicine after not taking it for longer than 2 weeks.

Korlym can make birth control pills less effective. Use a non-hormone method of birth control (such as a condom with spermicide or diaphragm with spermicide) while you are using this medicine and for at least 1 month after your treatment ends.

Korlym can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Progesterone-receptor antagonist; a synthetic derivative of norethindrone.1 2 3 4 5 6 7 8 9 19

Storage

Oral

25°C (may be exposed to 15–30°C).1

mifepristone should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

For patients using Mifeprex® tablets:

• mifepristone is given only by your doctor. You will not be allowed to take it at home. The entire treatment requires three visits to your doctor.
• At the first visit, you will be given one mifepristone tablet. Two days later at the second visit, you will be given four tablets of another medicine called misoprostol. Two weeks later at the third visit, your doctor will check to make sure you are no longer pregnant. This may include an ultrasound exam (sonogram).
• mifepristone will cause you to bleed and have cramps for about 2 to 4 weeks. Call your doctor if you have little or no vaginal bleeding after receiving the medicine.
• It is sometimes necessary to have a surgical abortion to completely end the pregnancy. You may also need to have surgery if there is any tissue left in your uterus after treatment with mifepristone.
• Tell your doctor if you are using an intrauterine device (IUD). It must be removed first before using mifepristone.

For patients using Korlym™ tablets:

• Your doctor will tell you how much of mifepristone to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.
• Swallow the tablet whole. Do not break, crush, or chew it. Take mifepristone with a meal.

Dosing

The dose of mifepristone 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 mifepristone. 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 (tablets):
  • For termination of pregnancy (70 days or less) taken together with misoprostol:
    • Adults—200 milligrams (mg) as a single dose on Day 1. This is followed 2 days later by 800 micrograms (mcg) (four-200 mcg tablets) of misoprostol as a single dose placed in the cheeks.
    • Children—Use is not recommended.
  • For treatment of hyperglycemia in patients with Cushing's syndrome:
    • Adults—At first, 300 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of mifepristone, 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.

Mifepristone is a synthetic steroid. At low doses, it competitively binds to the intracellular progesterone receptor, blocking the effects of progesterone. When used for the termination of pregnancy, this leads to contraction-inducing activity in the myometrium. In the absence of progesterone, mifepristone acts as a partial progesterone agonist. At high doses used for the treatment of hyperglycemia in patients with Cushing’s syndrome, mifepristone blocks the effect of cortisol at the glucocorticoid receptor (antagonizes the effects of cortisol on glucose metabolism) while at the same time increasing circulating cortisol concentrations.

Absorption

Oral: Rapid

Metabolism

Hepatic via CYP3A4 to three metabolites (active)

Excretion

Feces (83%); urine (9%)

Time to Peak

Oral: 90 minutes; Range: Single dose: 1-2 hours, Multiple doses: 1-4 hours

Half-Life Elimination

Single dose: Terminal: 18 hours following a slower phase where 50% eliminated between 12-72 hours; Multiple doses (600 mg/day): 85 hours

Protein Binding

98% to albumin and α1-acid glycoprotein