Korlym

Korlym is used to treat high blood sugar (hyperglycemia) caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and who have failed surgery or cannot have surgery. Korlym is not for people who have type 2 diabetes that is not caused by Cushing's syndrome. It is not known if Korlym is safe and effective in children.

Korlym contains mifepristone, a cortisol receptor blocker. Instead of lowering how much cortisol the body makes, it blocks cortisol from acting on its receptor in tissues throughout the body, which reduces the effects of excess cortisol, including its effect on blood sugar. Because the hormone's action is blocked rather than its level, blood cortisol stays high during treatment and cannot be used to judge how well the medicine is working. Korlym is taken once a day with food.

Korlym (mifepristone) received FDA approval on February 17, 2012 and is manufactured for Corcept Therapeutics.

Korlym (mifepristone) was studied in a single 24-week, open-label trial (one with no comparison group) called the SEISMIC study (NCT00569582), which tested the same medicine under its earlier development name, CORLUX, in 50 adults with endogenous Cushing's syndrome who had failed surgery or were not candidates for it.

• Among the 25 patients who had type 2 diabetes or glucose intolerance, 60% (15 of 25) responded with at least a 25% reduction in blood sugar during a glucose tolerance test, and average HbA1c fell by 1.1% from a starting average of 7.4%.
• Because the study was small and had no control group, improvements in other signs of Cushing's syndrome could not be clearly attributed to Korlym.

Korlym and Mifeprex both contain the same active ingredient, mifepristone, but they are approved for very different uses. Mifeprex is taken as a single dose or short course to end an early pregnancy, while Korlym is taken as a 300 mg tablet once daily on an ongoing basis to control high blood sugar in adults with Cushing's syndrome.

Korlym can cause serious side effects, including loss of a pregnancy. Women who can become pregnant must:

• have a negative pregnancy test before starting Korlym
• have a negative pregnancy test before restarting Korlym if they stop taking it for more than 14 days
• use a non-hormonal form of birth control while taking Korlym and for 1 month after stopping Korlym

Talk to your doctor about how to prevent pregnancy. Tell your doctor right away if you think you may be pregnant.

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

You should not drink grapefruit juice while you take Korlym. Grapefruit juice may increase the amount of Korlym in your blood and increase your chance of having side effects.

Do not take Korlym if you:

• are pregnant
• are taking simvastatin (Zocor, Vytorin, Simcor) or lovastatin (Mevacor, Altoprev, Advicor)
• are taking cyclosporine (Gengraf, Neoral, Restasis, Sandimmune), dihydroergotamine (Migranal), ergotamine (Ergomar, Migergot), fentanyl (Abstral, Actiq, Duragesic, Fentora, Lazanda, Onsolis, Sublimaze Preservative Free, Subsys), pimozide (Orap), quinidine (Nuedexta), sirolimus (Rapamune, Torisel), or tacrolimus (Prograf, Protopic)
• must take corticosteroid medicines for other serious medical problems
• are a woman who still has her uterus (womb) and have unexplained bleeding from your vagina, changes in the cells lining your uterus (endometrial hyperplasia), or cancer of the lining of your uterus (endometrial cancer)
• are allergic to mifepristone or any of the ingredients in Korlym

Talk to your doctor before taking Korlym if you have any of these conditions.

Before taking Korlym, tell your healthcare provider about all your medical conditions, including if you:

• are pregnant or plan to become pregnant
• have low potassium in your blood (hypokalemia)
• have or have had a bleeding problem or are taking medicines to thin your blood
• have or have had heart problems
• have had an organ transplant
• have been taking medicines called corticosteroids (cortisone, dexamethasone, methylprednisolone, prednisolone, prednisone)
• are breastfeeding or plan to breastfeed.

Tell your doctor about all of the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Serious side effects

Korlym can cause serious side effects, including:

• loss of pregnancy (see the most important information above)
• reduced effects of adrenal hormones (adrenal insufficiency). Korlym stops the adrenal hormone cortisol from working. Tell your doctor right away if you have symptoms such as unusual tiredness or weakness, nausea, fatigue, low blood pressure (hypotension), or low blood sugar (hypoglycemia).
• low blood potassium (hypokalemia). Your doctor should check your potassium level before you start Korlym and while you take it. Signs may include muscle weakness, aches, or cramps, and abnormal or irregular heartbeats (palpitations).
• bleeding from the vagina. Korlym may cause the lining of the uterus to become thick and may cause the uterus to bleed. Tell your doctor right away about any vaginal bleeding that is not normal for you.
• disruption of the menstrual cycle
• problems with the electrical system of the heart (QT interval prolongation)
• worsening of symptoms of other medical problems that are treated with corticosteroids, if you take corticosteroids and Korlym at the same time.

Common side effects

The most common side effects of Korlym include nausea, fatigue, headache, low potassium in the blood, pain in the arms and legs (arthralgia), vomiting, swelling of the arms and legs (peripheral edema), high blood pressure, dizziness, decreased appetite, and thickening of the lining of the uterus (endometrial hypertrophy).

Tell your doctor if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Korlym. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Using Korlym with certain other medicines can cause serious side effects. Korlym can interact with many other medicines, and some of these interactions are serious. Mifepristone affects liver enzymes (mainly CYP3A) that process a wide range of drugs, and its effects can last for about 2 weeks after the last dose. Especially tell your doctor if you take medicines to treat fungal infections (such as ketoconazole), depression, HIV infection, hepatitis C infection, certain bacterial infections, or high blood pressure, as well as steroid medicines such as prednisone and thyroid hormones.

Do not take Korlym with:

• simvastatin or lovastatin (cholesterol medicines)
• cyclosporine, sirolimus, or tacrolimus (used after an organ transplant)
• dihydroergotamine or ergotamine (migraine medicines)
• fentanyl (a strong pain medicine)
• pimozide (used for certain mental health conditions)
• quinidine (a heart rhythm medicine)
• hormonal birth control, which Korlym makes less effective (use a non-hormonal method instead)
• corticosteroids that are needed to treat another serious condition

Use with caution or with dose changes:

• Strong CYP3A inhibitors, such as ketoconazole, itraconazole, clarithromycin, and certain HIV and hepatitis C medicines, can raise Korlym levels. The Korlym dose is usually limited to 900 mg a day when one of these is needed.
• CYP3A inducers, such as rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's wort, should be avoided because they can lower Korlym levels.
• Blood thinners such as warfarin, NSAID pain relievers, and repaglinide (a diabetes medicine) may be affected by Korlym; your doctor may use the lowest dose and monitor you.
• Bupropion (for depression or quitting smoking) and efavirenz (for HIV) should be used with caution.
• Medicines that can affect heart rhythm (QT prolongation) should generally be avoided with Korlym.

Do not drink grapefruit juice while taking Korlym, as it may increase the amount of the medicine in your blood.

Tell your doctor and pharmacist about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements, before starting Korlym.

This is not a complete list of Korlym's interactions. Ask your doctor or pharmacist for advice, and do not start or stop any medicine without checking first.

• Store Korlym at room temperature, between 68 degrees F and 77 degrees F (20 degrees C to 25 degrees C).
• Keep Korlym and all medicines out of the reach of children.

Active ingredient: mifepristone

Inactive ingredients: silicified microcrystalline cellulose, sodium starch glycolate, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate, hypromellose, titanium dioxide, triacetin, D&C yellow 10 aluminum lake, polysorbate 80, and FD&C yellow 6 aluminum lake.

Korlym is manufactured for Corcept Therapeutics Incorporated, Redwood City, CA 94065. For more information, go to www.korlym.com or www.corcept.com, or call 1-855-456-7596.