What is mifepristone

Mifepristone also known as RU-486, is used in a regimen together with misoprostol to end a pregnancy (induce medical abortion) that is less than 70 days in duration. Mifepristone works by stopping the supply of hormones that maintains the interior of the uterus. Without these hormones, the uterus cannot support the pregnancy and the contents of the uterus are expelled. Mifepristone alone, without misoprostol, is also used to control high blood sugar (hyperglycemia) in patients with Cushing’s syndrome who also have type 2 diabetes and have failed surgery or are not candidates for surgery, where it is given in a higher dose and for extended periods.

Mifepristone is available only with your doctor’s prescription.

Mifepristone was first approved for use in France in 1988, in Great Britain in 1991, Sweden in 1992, and the United States in 2000. The current indications for mifepristone with misoprostol combination is for medical termination of intrauterine pregnancy through 70 days of gestation. Mifepristone is available in tablets of 200 mg under the brand name Mifeprex. The currently recommended dose of mifepristone for inducing a medical abortion is as a single 200 mg tablet followed 24 to 48 hours later by buccal administration of 800 mcg of misoprostol (a prostaglandin agonist). Mifepristone has been used off-label as a means of emergency contraception, but is not approved for that use.

Mifepristone side effects are common, but generally mild-to-moderate in severity and can include uterine bleeding, nausea, vomiting, abdominal cramps, weakness, fever, headache, diarrhea, and dizziness. Rare, but potentially severe adverse events include serious uterine bleeding and serious bacterial infections, failed abortion and need for hospitalization. Contraindications to use of mifepristone/misoprostol include pregnancy beyond 70 days (10 weeks), ectopic pregnancy, presence of an intrauterine device, adrenal failure, porphyria and use of anticoagulants. Because of the serious nature of these side effects, mifepristone/misoprostol is available only through a Risk Evaluation and Mitigation Strategy program to certified prescribers.

Mifepristone was also approved for use to control high blood sugar (hyperglycemia) in patients with Cushing’s syndrome who also have type 2 diabetes and have failed surgery or are not candidates for surgery in 2012 and is available in 300 mg tablets under the brand name Korlym. The recommended dose is 300 mg once daily initially with subsequent increases based upon efficacy and tolerance to a maximum of 1200 mg daily. Adverse events are not uncommon but generally mild and manageable, including nausea, vomiting, anorexia, fatigue, headache, arthralgia, peripheral edema, hypertension, dizziness, and hypokalemia. Severe adverse reactions include termination of pregnancy, adrenal insufficiency, vaginal bleeding, endometrial changes and QTc interval prolongation. Mifepristone is metabolized by CYP 3A4 and 2C8/2C9 and has many drug-drug interactions.

Abortion pill mifepristone

Mifepristone is used in combination with misoprostol (Cytotec) to end an early pregnancy. Early pregnancy means it has been 70 days or less since your last menstrual period began. Mifepristone is in a class of medications called antiprogestational steroids. It works by blocking the activity of progesterone, a substance your body makes to help continue pregnancy.

Mifepristone is also available as another product (Korlym), which is used to control hyperglycemia (high blood sugar) in people with a certain type of Cushing’s Syndrome in which the body makes too much of the hormone cortisol. This monograph only gives information about mifepristone (Mifeprex), which is used alone or in combination with another medication to end an early pregnancy. If you are using mifepristone to control hyperglycemia caused by Cushing’s syndrome, read the monograph entitled mifepristone (Korlym) that has been written about this product.

Mifepristone comes as a tablet to take by mouth. You will take one tablet of mifepristone once on the first day. Within 24 to 48 hours after taking mifepristone, you will apply four tablets in total of another medication called misoprostol buccally (between the gum and cheek) by placing two tablets in each cheek pouch for 30 minutes, then swallowing the remaining content with water or another liquid. Make sure that you are in an appropriate location when you take misoprostol because vaginal bleeding, cramps, nausea, and diarrhea usually begins within 2 to 24 hours after taking it but could begin within 2 hours. Vaginal bleeding or spotting usually lasts for 9 to 16 days but can last for 30 days or longer. You must go back to your doctor for an exam or ultrasound 7 to 14 days after taking mifepristone to confirm that the pregnancy has ended and to check the amount of bleeding. Take mifepristone exactly as directed.

Mifepristone special precautions

Before taking mifepristone:

• tell your doctor if you are allergic to mifepristone (hives, rash, itching, swelling of the face, eyes, mouth, throat, hands; difficulty breathing or swallowing); misoprostol (Cytotec, in Arthrotec); other prostaglandins such as alprostadil (Caverject, Edex, Muse, others), carboprost tromethamine (Hemabate), dinoprostone (Cervidil, Prepidil, Prostin E2), epoprostenol (Flolan, Veletri), latanoprost (Xalatan), treprostinil (Orenitram, Remodulin, Tyvaso);any other medications, or any of the ingredients in mifepristone tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
  tell your doctor if you are taking corticosteroids such as beclomethasone (Beconase, QNASL, QVAR), betamethasone (Celestone), budesonide (Entocort, Pulmicort, Uceris), cortisone, dexamethasone, fludrocortisone, flunisolide (Aerospan HFA), fluticasone (Advair, Flovent, Veramyst, others), hydrocortisone (Cortef, Solu-Cortef, U-Cort, others), methylprednisolone (Medrol, Depo-Medrol), prednisolone (Omnipred, Prelone, others), prednisone (Rayos), and triamcinolone (Kenalog, others). Your doctor will probably tell you not to take mifepristone.
• tell your doctor what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), midazolam, or triazolam (Halcion); buspirone; calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Cartia, Diltzac, others), felodipine, nifedipine (Adalat, Afeditab CR, Procardia), nisoldipine (Sular), or verapamil (Calan, Verelan, in Tarka); carbamazepine (Equetro, Tegretol, Teril, others); chlorpheniramine (antihistamine in cough and cold products); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor, in Caduet), lovastatin (Altoprev, in Advicor), or simvastatin (Simcor, Zocor, in Vytorin); clarithromycin (Biaxin, in Prevpac); cyclosporine (Gengraf, Neoral, Sandimmune); erythromycin (E.E.S., Erythrocin, others); haloperidol; furosemide; HIV protease inhibitors such as indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra, others), or saquinavir (Invirase); itraconazole (Onmel, Sporanox); ketoconazole (Nizoral); methadone (Dolophine, Methadose); nefazodone; phenobarbital; phenytoin (Dilantin, Phenytek); pimozide (Orap); propranolol (Hemangeol, Inderal, Innopran); quinidine (in Nuedexta); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); rifabutin (Mycobutin); tacrolimus (Astagraf, Prograf, Protopic, others); tamoxifen (Soltamox); trazodone; or vincristine (Marqibo Kit). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s wort.
• tell your doctor if you have or have ever had an ectopic pregnancy (‘tubal pregnancy’ or pregnancy outside the uterus), adrenal failure (problems with your adrenal glands), or porphyria (an inherited blood disease that may cause skin or nervous system problems). Your doctor will probably tell you not to take mifepristone. Also, tell your doctor if you have had an intrauterine device (IUD) inserted. It must be removed before you take mifepristone.
• you should know that it is possible that mifepristone will not end your pregnancy. Your doctor will check to be sure that your pregnancy has ended when you return for your follow-up appointment after you take mifepristone. If you are still pregnant after taking mifepristone, there is a chance that your baby may be born with birth defects. If your pregnancy has not ended completely, your doctor will discuss other options to consider. You may choose to wait, take another dose of misoprostol or have surgery to end the pregnancy. If you take a repeat dose of misoprostol, you must have a follow-up visit with your doctor in 7 days after that dose to be sure that your pregnancy has ended.
• tell your doctor if you are breastfeeding.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you have taken mifepristone.
• you should know that after ending a pregnancy with mifepristone, you can become pregnant again right away, even before your period returns. If you do not want to become pregnant again, you should begin using birth control as soon as this pregnancy ends or before you start having sexual intercourse again.

Pregnancy

Pregnancy Category X: Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

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.

Special dietary instructions

Do not take mifepristone with grapefruit juice. Talk to your doctor about drinking grapefruit juice after taking mifepristone.

What should I do if I forget a dose?

You will only take mifepristone in your doctor’s office or clinic, so you do not have to worry about forgetting to take a dose at home.

Drug Interactions

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 mifepristone, 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 mifepristone 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.

• Amisulpride
• Bepridil
• Cisapride
• Cyclosporine
• Dihydroergotamine
• Dronedarone
• Ergotamine
• Fentanyl
• Fluconazole
• Ketoconazole
• Lovastatin
• Mesoridazine
• Pimozide
• Piperaquine
• Posaconazole
• Quinidine
• Saquinavir
• Simvastatin
• Sirolimus
• Sparfloxacin
• Tacrolimus
• Terfenadine
• Thioridazine

Using mifepristone 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.

• Alfentanil
• Amiodarone
• Anagrelide
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Azithromycin
• Benzhydrocodone
• Boceprevir
• Buprenorphine
• Buserelin
• Carbamazepine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cilostazol
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clozapine
• Cobicistat
• Codeine
• Colchicine
• Conivaptan
• Crizotinib
• Dabrafenib
• Dasabuvir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Digoxin
• Dihydrocodeine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Efavirenz
• Encorafenib
• Erythromycin
• Escitalopram
• Fingolimod
• Flecainide
• Fluoxetine
• Foscarnet
• Fosphenytoin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydrocodone
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Idelalisib
• Ifosfamide
• Iloperidone
• Imipramine
• Indinavir
• Inotuzumab Ozogamicin
• Itraconazole
• Ivabradine
• Ivosidenib
• Lapatinib
• Leuprolide
• Levofloxacin
• Lofexidine
• Lopinavir
• Lumefantrine
• Macimorelin
• Mefloquine
• Meperidine
• Methadone
• Metronidazole
• Moxifloxacin
• Nafarelin
• Naloxegol
• Nefazodone
• Nelfinavir
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olaparib
• Ondansetron
• Osimertinib
• Oxycodone
• Paliperidone
• Panobinostat
• Pasireotide
• Pazopanib
• Pentazocine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pitolisant
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinine
• Ranolazine
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Salmeterol
• Sertraline
• Sevoflurane
• Simeprevir
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John’s Wort
• Sufentanil
• Sulpiride
• Sunitinib
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Toremifene
• Tramadol
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Vinflunine
• Voriconazole
• Ziprasidone
• Zuclopenthixol

Using mifepristone 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.

• Alprazolam
• Fluvastatin

Other Interactions

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.

Other Medical Problems

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

• Abnormal vaginal bleeding, history of or
• Adrenal failure, chronic or
• Bleeding problems or
• Ectopic pregnancy (eg, a pregnancy that develops in fallopian tubes instead of the uterus) or
• Endometrial hyperplasia or cancer or
• Lower abdominal mass that is undiagnosed or
• Porphyria (an enzyme problem)—Should not be used in patients with these conditions.
• Adrenal problems or
• Autoimmune disorders or
• Diabetes or
• Heart failure or
• Heart or blood vessel disease (eg, coronary vascular disease) or
• Heart rhythm problem (eg, QT prolongation) or
• Hypertension (high blood pressure) or
• Lung disease—Use with caution. May make these conditions worse.
• Anemia, severe or
• Inability of blood to clot properly or
• Poor blood circulation—Mifeprex® causes heavy bleeding in a small portion of users, this may be intensified in patients with bleeding disorders.
• Hypokalemia (low potassium in the blood)—Should be corrected first before using this medicine.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Mifepristone for high blood sugar in Cushing’s syndrome

Mifepristone (Korlym) is used to treat hyperglycemia (high blood sugar) in people with a certain type of Cushing’s syndrome in which the body makes too much cortisol (a hormone) and who have failed surgery or cannot have surgery to treat this condition. Mifepristone is in a class of medications called cortisol receptor blockers. It works by blocking the activity of cortisol.

Mifepristone is also available as another product (Mifeprex) that is used alone or in combination with another medication to end an early pregnancy. This monograph only gives information about mifepristone (Korlym) used to control hyperglycemia in people with a certain type of Cushing’s syndrome. If you are using mifepristone to terminate a pregnancy, read the monograph entitled mifepristone (Mifeprex), which has been written about this product.

Mifepristone comes as a tablet to take by mouth. It is usually taken once a day with a meal. Take mifepristone at around the same time 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 mifepristone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them. Tell your doctor or pharmacist if you are not able to swallow the tablets whole.

Your doctor will start you on a low dose of mifepristone and gradually increase your dose, not more often than once every 2 to 4 weeks. If you stop taking mifepristone, call your doctor. Your doctor may have to start you again on the lowest dose of mifepristone and gradually increase your dose.

Mifepristone can control your condition but does not cure it. It may take 6 weeks or longer before you feel the full benefit of mifepristone. Continue to take mifepristone even if you feel well.

Mifepristone special precautions

Before taking mifepristone:

• tell your doctor if you are allergic to mifepristone, any other medications, or any of the ingredients in mifepristone tablets. Ask your pharmacist or check the manufacturer’s patient information for a list of the ingredients.
• tell your doctor if you are taking any of the following medications or have taken them in the last two weeks: corticosteroids such as betamethasone (Celestone), budesonide (Entocort), cortisone (Cortone), dexamethasone (Decadron, Dexpak, Dexasone, others), fludrocortisone (Floriner), hydrocortisone (Cortef, Hydrocortone), methylprednisolone (Medrol, Meprolone, others), prednisolone (Prelone, others), prednisone (Deltasone, Meticorten, Sterapred, others), and triamcinolone (Aristocort, Azmacort); medications that suppress the immune system such as cyclosporine (Neoral, Sandimmune), sirolimus (Rapamune), and tacrolimus (Prograf); dihydroergotamine (D.H.E. 45, Migranal); ergotamine (Ergomar, in Cafergot, in Migergot); fentanyl (Duragesic); lovastatin (Mevacor); pimozide (Orap); quinidine (Quinidex); and simvastatin (Zocor). Your doctor will probably tell you not to take mifepristone 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 have taken in the last two weeks. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), or voriconazole (Vfend); aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); bupropion (Wellbutrin); ciprofloxacin (Cipro); clarithromycin (Biaxin); conivaptan (Vaprisol); diltiazem (Cardizem); erythromycin (E.E.S., E-Mycin, Erythrocin); fluvastatin (Lescol); hormonal contraceptives such as birth control pills, implants, patches, rings, or injections; medications for hepatitis C such as boceprevir (Victrelis) and telaprevir (Incivek); medications for HIV or AIDS such as amprenavir (Agenerase), atazanavir (Reyataz), efavirenz (Sustiva), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir and ritonavir combination (Kaletra), nelfinavir (Viracept), ritonavir (Norvir), and saquinavir (Fortovase, Invirase); medications for seizures such as carbamazepine (Tegretol), phenobarbital (Luminal, Solfoton), phenytoin (Dilantin); medications for tuberculosis such as rifabutin (Mycobutin), rifampin (Rifadin, Rimactane, in Rifamate, in Rifater) and rifapentine (Priftin); nefazodone (Serzone); repaglinide (Prandin); telithromycin (Ketek); and verapamil (Calan, Isoptin, others). Many other medications may also interact with mifepristone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John’s Wort.
• tell your doctor if you have ever had an organ transplant or if you have or ever had thyroid disease. If you are a woman and have not had surgery to remove your uterus, tell your doctor if you have or have ever had unexplained vaginal bleeding, endometrial hyperplasia (overgrowth of the lining of the uterus), or endometrial cancer (cancer of the lining of your uterus). Your doctor will probably tell you not to take mifepristone.
• tell your doctor if you have or have ever had heart failure, a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), low potassium in your blood, adrenal insufficiency(condition in which the adrenal glands do not produce enough of certain hormones needed for important body functions), a bleeding disorder, or liver, kidney, or heart disease.
• tell your doctor if you are breast-feeding.

Special dietary instructions

Do not eat grapefruit or drink grapefruit juice while you are taking mifepristone.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

How does mifepristone work?

Mifepristone is a potent synthetic steroidal antiprogesterone which is used as a single dose in combination with misoprostol, a prostaglandin analogue, to induce medical abortion. Mifepristone antagonizes the action of progesterone by competing with its binding to its receptor. The sudden loss of progesterone activity during pregnancy causes a series of intrauterine and cervical changes that result in termination of pregnancy. Misoprostol is a prostaglandin analogue that causes uterine contraction which completes the medical abortion. In multiple large prospective studies, the administration of a single dose of mifepristone followed within 24 to 48 hours by a prostaglandin agonist safely terminated early pregnancy in more than 90% of women.

Mifepristone (without misoprostol) is also approved for use in Cushing syndrome caused by excessive production of glucocorticoids. Mifepristone also blocks the actions of a hormone called cortisol, which can reduce certain side effects caused by excess cortisol in the body. Mifepristone has antiglucocorticoid receptor activity and has been found to alleviate high blood sugar (hyperglycemia) in adults with hypercortisolism (Cushing’s syndrome) who also have type 2 diabetes mellitus and glucose intolerance or type 2 diabetes who have failed to respond or are not candidates for surgical therapy.

Mifepristone uses

Mifepristone also known as RU-486, is used in a regimen together with misoprostol to end a pregnancy (induce medical abortion) that is less than 70 days in duration. Mifepristone works by stopping the supply of hormones that maintains the interior of the uterus. Without these hormones, the uterus cannot support the pregnancy and the contents of the uterus are expelled. Mifepristone alone, without misoprostol, is also used to control high blood sugar (hyperglycemia) in patients with Cushing’s syndrome who also have type 2 diabetes and have failed surgery or are not candidates for surgery, where it is given in a higher dose and for extended periods.

Mifepristone is also sometimes used to end pregnancies when more than 70 days have passed since the woman’s last menstrual period; as an emergency contraceptive after unprotected sexual intercourse (‘morning-after pill’); to treat tumors of the brain, endometriosis (growth of uterus tissue outside the uterus), or fibroids (noncancerous tumors in the uterus); or to induce labor (to help start the birth process in a pregnant woman). Talk to your doctor about the possible risks of using this drug for your condition.

Mifepristone dosage

Adult Dose for Abortion

Use: Medical termination of intrauterine pregnancy through 70 days gestation

Brand MIFEPREX:

• Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose
• Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).

Post-treatment Assessment Day 7 to 14:

• A follow-up visit approximately 7 to 14 days after the administration of mifepristone is necessary to confirm complete termination of pregnancy and to evaluate the degree of bleeding.
• Termination of pregnancy can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
• The existence of debris in the uterus (e.g., if seen on ultrasonography) following the treatment procedure will not necessarily require surgery for its removal.
• Patients should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Heavy bleeding for a median duration of 2 days has been reported. Some women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at the time of follow-up, however, could indicate an incomplete abortion.
• If complete expulsion has not occurred, but the pregnancy is not ongoing, another dose of misoprostol 800 mcg buccally may be administered. A follow-up visit in approximately 7 days to assess for complete termination is recommended.
• Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion.

Comments.

• Medication for cramps or gastrointestinal symptoms may be needed during the period immediately following the administration of misoprostol.
• The effectiveness of the regimen may be lower if misoprostol is administered less than 24 hours or more than 48 hours after mifepristone (MIFEPREX) administration.
• Most women will expel the pregnancy within 2 to 24 hours of taking misoprostol; select appropriate location for the patient to be when misoprostol is administered, taking into account that expulsion could begin within 2 hours of administration.
• For purposes of this treatment (pregnancy termination), pregnancy is dated from the first day of the last menstrual period.
• The duration of pregnancy may be determined from menstrual history and clinical examination.
• Assess the pregnancy by ultrasonographic scan if the duration of pregnancy is uncertain or if ectopic pregnancy is suspected.
• Remove any intrauterine device (IUD) before beginning treatment with this drug.

Adult Dose for Cushing’s Syndrome

Use: Control of hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery

Brand KORLYM:

• Initial dose: 300 mg orally once a day
• Maximum dose: 1200 mg or 20 mg/kg once a day

Comments:

• Dose increases should occur once every 2 to 4 weeks. For additional information of dose titration refer to the Dose Adjustment section.

Pediatric Dose for Abortion

Use: Medical termination of intrauterine pregnancy through 70 days gestation

Brand MIFEPREX:

• Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose
• Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).

Post-treatment Assessment Day 7 to 14:

• A follow-up visit approximately 7 to 14 days after the administration of mifepristone is necessary to confirm complete termination of pregnancy and to evaluate the degree of bleeding.
• Termination of pregnancy can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
• The existence of debris in the uterus (e.g., if seen on ultrasonography) following the treatment procedure will not necessarily require surgery for its removal.
• Patients should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Heavy bleeding for a median duration of 2 days has been reported. Some women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at the time of follow-up, however, could indicate an incomplete abortion.
• If complete expulsion has not occurred, but the pregnancy is not ongoing, another dose of misoprostol 800 mcg buccally may be administered. A follow-up visit in approximately 7 days to assess for complete termination is recommended.
• Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion.

Comments.

• Medication for cramps or gastrointestinal symptoms may be needed during the period immediately following the administration of misoprostol.
• The effectiveness of the regimen may be lower if misoprostol is administered less than 24 hours or more than 48 hours after mifepristone (MIFEPREX) administration.
• Most women will expel the pregnancy within 2 to 24 hours of taking misoprostol; select appropriate location for the patient to be when misoprostol is administered, taking into account that expulsion could begin within 2 hours of administration.
• For purposes of this treatment (pregnancy termination), pregnancy is dated from the first day of the last menstrual period.
• The duration of pregnancy may be determined from menstrual history and clinical examination.
• Assess the pregnancy by ultrasonographic scan if the duration of pregnancy is uncertain or if ectopic pregnancy is suspected.
• Remove any intrauterine device (IUD) before beginning treatment with this drug.

Renal Dose Adjustments

• Brand KORLYM: The maximum dose should not exceed 600 mg per day in renally impaired patients.
• Brand MIFEPREX: Data not available

Liver Dose Adjustments

Brand KORLYM:

• Mild to moderate liver dysfunction: The maximum dose should not exceed 600 mg per day.
• Severe liver dysfunction: Not recommended

Brand MIFEPREX: Data not available

Dose Adjustments

Brand KORLYM:

• Dose increases should be based on tolerability and degree of improvement in Cushing’s syndrome manifestations.
• Changes in glucose control, anti-diabetic medication requirements, insulin levels, and psychiatric symptoms may provide an early assessment of response (within 6 weeks) and may help guide early dose titration.
• Improvements in cushingoid appearance, acne, hirsutism, striae, and body weight occur over a longer period of time and, along with measures of glucose control, may be used to determine dose changes beyond the first 2 months of therapy.
• Careful and gradual titration of KORYLM accompanied by monitoring for recognized adverse reactions may reduce the risk of severe adverse reactions.
• Dose reduction or even dose discontinuation may be needed in some clinical situations. If treatment is interrupted, it should be reinitiated at the lowest dose (300 mg). If treatment was interrupted because of adverse reactions, the titration should aim for a dose lower than the one that resulted in treatment interruption.
• If combination with strong CYP450 3A inhibitors is necessary, the dose should be limited to 300 mg per day.

Mifepristone side effects

Mifepristone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• vaginal bleeding or spotting
• cramps
• pelvic pain
• vaginal burning, itching, or discharge headache
• vomiting
• dry mouth
• diarrhea
• constipation
• joint or muscle pain
• swelling of the hands, feet, ankles, or lower legs
• rash
• itching

Some side effects can be serious. If you experience any of the symptoms mentioned below including in the IMPORTANT WARNING sections, call your doctor immediately or get emergency medical treatment:

• nausea
• loss of appetite
• dizziness or lightheadedness
• unusual tiredness or weakness
• nervousness or irritability
• shakiness
• sweating
• muscle weakness, aches, or cramps
• rapid, irregular, or pounding heartbeats
• unexpected vaginal bleeding or spotting
• shortness of breath

Mifepristone may cause other side effects. Call your doctor if you have any unusual problems while taking mifepristone.

Symptoms of mifepristone overdose may include the following:

• dizziness
• fainting
• blurred vision
• nausea
• tiredness
• weakness
• shortness of breath
• fast heartbeat