for signs and symptoms of adrenal insufficiency, including weakness, nausea, increased fatigue, hypotension, and hypoglycemia If adrenal insufficiency is suspected, discontinue treatment with drug immediately and administer glucocorticoids without delay High doses of supplemental glucocorticoids may be needed to overcome glucocorticoid receptor blockade produced by mifepristone Factors considered in deciding on duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hr). Treatment at a lower dose can be resumed after resolution of adrenal insufficiency; patients should also be evaluated for precipitating causes of hypoadrenalism (infection, trauma, etc) Hypokalemia In a study of patients with Cushing’s syndrome, hypokalemia observed Hypokalemia should be corrected prior to initiating therapy; during administration, serum potassium should be measured 1-2 weeks after starting or increasing dose and periodically thereafter Hypokalemia can occur at any time during treatment; mifepristone-induced hypokalemia should be treated with intravenous or oral potassium supplementation based on event severity If hypokalemia persists in spite of potassium supplementation, consider adding mineralocorticoid antagonists Pregnancy Drug contraindicated in pregnancy because use results in pregnancy loss; there are no data that assess risk of birth defects in women exposed to drug during pregnancy Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator Pregnancy testing Due to its anti-presentational activity, drug causes pregnancy loss; perform pregnancy testing before initiation of treatment or if treatment interrupted for more than 14 days in females of reproductive potential Contraception Recommend non-hormonal contraception for duration of treatment and for one month after stopping treatment; drug interferes with effectiveness of hormonal contraceptives Animal data Administered to pregnant mice, rats, and rabbits during organogenesis caused pregnancy loss in all species at clinically relevant doses based on body surface area comparisons; inhibition of both endogenous and exogenous progesterone by mifepristone at progesterone receptor results in pregnancy loss; if used during pregnancy or if patient becomes pregnant while taking drug, patient should be apprised of potential hazard to a fetus Estimated risk of fetal loss is elevated in patients with active Cushing’s syndrome (24-30%), and risk of major birth defects is unknown; in the U.S. general population, estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively Lactation Drug is present in human milk, however, there are no data on amount of mifepristone in human milk, effects on breastfed infant, or on milk production during long term use of mifepristone; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for Korlym and any potential adverse effects on breastfed child from drug or from the underlying maternal condition To minimize exposure to a breastfed infant, women who discontinue or interrupt treatment may consider pumping and discarding milk during treatment and for 18-21 days (5-6 half-lives) after last dose, before breastfeedingPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Stimulate uterine contractility: antiprogestin; also increases prostaglandins by inhibiting prostaglandin dehydrogenase Blocks cortisol receptor binding, and thereby reduces excess cortisol effects (eg, hyperglycemia) associated with endogenous Cushing syndrome Absorption Peak Plasma Time: 1-2 hr (single dose); 1-4 hr (multiple doses) Peak Plasma Concentration: 2-8 hr Distribution Protein Bound: >99% to alpha-1-acid glycoprotein; 96-99% (active metabolites) Distributed to other tissues including CNS Metabolism Extensively metabolized by CYP3A4 Metabolized to 3 active metabolites, of which 2 are the product of demethylation, while a third active metabolite results from hydroxylation In addition to being a CYP3A4 substrate, it also inhibits and induces CYP3A4 Elimination Half-life: 20 hr (single dose); 85 hr (parent drug following multiple doses) Excretion: 90% feces Oral Administration (Mifeprex) 200 mg PO once, followed 24-48 hr later by misoprostol buccal administration Follow up with healthcare provider 7-14 days after taking Mifeprex Buccal administration (misoprostol) Because most women will expel the pregnancy within 2-24 hr of taking misoprostol, discuss with the patient an appropriate location for her to be when she takes the misoprostol, taking into account that expulsion could begin within 2 hr of administration Administer misoprostol 800 mcg buccally within 24-48 hr after taking Mifeprex The effectiveness of the regimen may be lower if misoprostol is administered <24 hr or >48 hr after mifepristone administration Tell the patient to place two 200 mcg misoprostol tablets in each cheek pouch (the area between the cheek and gums) for 30 minutes and then swallow any remnants with water or another liquid During the period immediately following the administration of misoprostol, the patient may need medication for cramps or GI symptoms Oral Administration (Korlym) Always take with a meal Must be taken as a single daily dose Swallow tablet whole, do not split, crush, or chew Dose reduction or discontinuation may be needed in some clinical situations; if dosage is interrupted, reinitiate at the lowest dose (ie, 300 mg/day) BRAND FORM. UNIT PRICE PILL IMAGE Korlym oral- 300 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationmifepristone oral MIFEPRISTONE - ORAL (MIF-e-PRIS-tone) COMMON BRAND NAME(S): Mifeprex WARNING: Rarely, serious medical problems can occur when a pregnancy ends, including sometimes fatal infections and bleeding. Read the Medication Guide, read and sign the Patient Agreement, and consult your doctor if you have any questions. To receive this medication in the United States, you must understand, agree to, and carefully follow the requirements of the Mifepristone REMS Program. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations.Your doctor must give you clear instructions about who to call and what to do in case of an emergency (such as severe bleeding, infection). If you go to the emergency room or visit another health care professional, show them the Medication Guide so they know you are trying to end your pregnancy.Get medical help right away if you experience symptoms such as severe abdominal pain, fainting, fast heartbeat, fever lasting more than 4 hours. You may have a very serious infection even if you do not have a fever. Get medical help right away if you have abdominal pain or feel sick (for example, if you have nausea, vomiting, diarrhea, weakness) more than 24 hours after taking the second drug (misoprostol), even if you do not have a fever. Also get medical help right away if you have continued heavy bleeding, which may be a sign the pregnancy has not ended or other serious medical problem. You may need surgery or other medical care. See also Side Effects section. USES: Mifepristone (also known as RU 486) is used to end a pregnancy during the early part of a pregnancy. It is used up to week 10 of pregnancy (up to 70 days after the first day of your last menstrual period). Mifepristone blocks a natural substance (progesterone) that is needed for your pregnancy to continue. It is usually used together with another medicine called misoprostol.Mifepristone must not be used if you have a rare abnormal pregnancy that is outside the womb (ectopic pregnancy). It will not end the pregnancy in this case. It may cause an ectopic pregnancy to rupture, resulting in very serious bleeding. HOW TO USE: Read the Medication Guide provided by your doctor before you start using mifepristone. Keep the guide to reread if needed. Read and sign the Patient Agreement form provided by your doctor. If you have any questions, consult your doctor or pharmacist.You must visit the doctor's office at least 2 times to complete your treatment and important examinations. This treatment is only given under direct medical supervision. Learn about who to call and what to do in case of an emergency.Your doctor may order an ultrasound to make sure your pregnancy is less than 10 weeks and is not outside the womb (ectopic).Take mifepristone by mouth as directed by your doctor, usually as a single dose. After taking mifepristone, your doctor should direct you to wait 24 to 48 hours before taking another medication (misoprostol) by mouth as a single dose. The medications may not work well if you take misoprostol sooner than 24 hours after taking mifepristone or later than 48 hours after taking mifepristone. Follow your doctor's instructions carefully. Heavy vaginal bleeding does not mean that the pregnancy has ended.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.It is important that you return for a follow-up visit within 7 to 14 days after taking mifepristone, even if you are not having any problems.If the pregnancy has not ended, or there are serious medical problems, surgery may be needed. If the treatment fails and the pregnancy continues until birth, there is a risk of birth defects. SIDE EFFECTS: See also Warning section.Nausea, vomiting, diarrhea, weakness, or dizziness may occur. If these effects last longer than the first 24 hours after taking the second drug (misoprostol), get medical help right away because they can be signs of a serious medical problem.Bleeding and cramping are expected during this treatment. Usually, the symptoms mean the drugs are working. However, sometimes you can have cramps and bleeding and still be pregnant. You must return for all of your follow-up visits with your doctor. Nausea and cramping may get worse in the 24 hours after you take the second drug (misoprostol). Your doctor may direct you to take other medication to help with these symptoms. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Bleeding and spotting may last up to 30 days and may be much heavier than a normal period. In very few cases, this bleeding will need to be stopped by surgery. Get medical help right away if you bleed enough to soak through 2 thick, full-size sanitary pads each hour for 2 hours in a row, or if you are concerned about heavy bleeding.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Get medical help right away if you have any very serious side effects, including: fever of 100.4 degrees F (38 degrees C) or higher, fainting, fast heartbeat, stomach/abdominal pain or tenderness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking mifepristone, tell your doctor if you are allergic to it; or to misoprostol; or to other progestins (such as norethindrone); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: undiagnosed abdominal growth (adnexal mass), adrenal gland problem, certain blood disorder (inherited porphyrias), bleeding problems, low blood count (anemia).If you are using an IUD (intrauterine birth control device), it should be removed before mifepristone treatment begins.This drug must be used only if you can easily reach adequate emergency medical services in case you have a serious medical problem.This drug may make you dizzy. Alcohol or marijuana