Mifepristone

Mifepristone is a synthetic steroid. The Mifeprex brand of mifepristone is indicated for the medical termination of intrauterine pregnancy through 70 days gestation in combination with misoprostol.

The Korlym brand of mifepristone is indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.

Mifepristone is available under the following different brand names: Mifeprex, Korlym, and RU486.

Dosages of Mifepristone:

Dosage Forms and Strengths

• 200 mg (Mifeprex)
• 300 mg (Korlym)

Dosing Considerations – Should be Given as Follows:

Pregnancy Termination

• Mifeprex: Indicated for the medical termination of intrauterine pregnancy through 70 days gestation in combination with misoprostol
• Day 1: 200 mg of mifepristone orally as a single dose under physician supervision
• Days 2-3: 800 mcg of misoprostol in the cheek (buccally) once as a single dose; must be administered a minimum of 24 hours and a maximum of 48 hours following mifepristone dose on day 1 (see Administration)
• Days 7-14
  • Must return for a follow-up visit to confirm complete termination has occurred by medical history, clinical examination, hCG testing, or ultrasonographic scan
  • If complete expulsion has not occurred, but the pregnancy is not ongoing, women may be treated with another dose of misoprostol 800 mcg in the cheek (buccally) with follow-up in approximately 7 days
  • Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion
  • Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion

Dosing Considerations

• Pregnancy is dated from the first day of the last menstrual period
• 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 treatment
• Because most women will expel the pregnancy within 2-24 hours 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 hours of administration

Cushing Syndrome

• Korlym: Indicated to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery
• 300 mg orally once/day initially; may dose to a maximum of 1200 mg/day, but should not exceed 20 mg/kg/day
• An increase in dose should not occur more frequently than every 2-4 weeks and should be based on an assessment of glucose control, anti-diabetic medication requirements, insulin levels, and psychiatric symptoms

Dosage Modifications (Korlym)

Coadministration with strong CYP3A inhibitors: Not to exceed 300 mg/day

Renal impairment: No change in initial dose; limit maximum dose to 600 mg orally once/day

Hepatic impairment

• Mild-to-moderate: No change in initial dose; limit maximum dose to 600 mg orally once/day
• Severe: Do not use

Pediatric: Safety and efficacy not established

There are no known side effects of mifepristone.

Common side effects of mifepristone (Mifeprex) include:

• Abdominal cramping
• Allergic reactions such as the closing of the throat, swelling of the lips, and tongue, or face
• Anemia
• Anxiety
• Back pain
• Decreased hemoglobin greater than 2 g/dL
• Diarrhea
• Dizziness
• Fainting
• Fatigue
• Headache
• Indigestion
• Insomnia
• Leg pain
• Nausea
• Pelvic pain
• Rigors
• Sinusitis
• Stomach pain
• Tired feeling
• Uterine bleeding
• Uterine cramping
• Vaginal discharge
• Vaginitis
• Viral infection
• Vomiting
• Weakness

Common side effects of mifepristone (Korlym) include:

• Abdominal/stomach pain
• Abnormal thyroid function test
• Abnormal vaginal bleeding
• Adrenal insufficiency
• Anxiety
• Back pain
• Constipation
• Decreased appetite
• Diarrhea
• Dizziness
• Drowsiness
• Dry mouth
• Endometrial hypertrophy
• Extremity pain
• Fatigue
• Feeling unwell (malaise)
• Gastroesophageal reflux (GERD)
• Headache
• High blood pressure (hypertension)
• Increased triglycerides
• Insomnia
• Itching
• Joint pain
• Lack of energy
• Loss of appetite
• Low blood potassium (hypokalemia)
• Low blood sugar (hypoglycemia)
• Low potassium levels
• Muscle pain
• Muscle weakness
• Musculoskeletal chest pain
• Nausea
• Pain
• Potential for heart conduction abnormalities
• Rash
• Runny or stuffy nose
• Shortness of breath
• Side (flank) pain
• Sinusitis
• Sleep problems (insomnia)
• Sore throat
• Swelling (edema, pitting edema)
• Swelling of extremities
• Thirst
• Vomiting

Postmarketing side effects of mifepristone reported include:

• Skin swelling

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Mifepristone has severe interactions with at least 44 different drugs.

Serious interactions of mifepristone include:

• afatinib
• atorvastatin
• deutetrabenazine
• eluxadoline
• fluvastatin
• histrelin
• idelalisib
• mefloquine
• nafarelin
• panobinostat
• pimavanserin
• pomalidomide
• ribociclib
• riociguat
• rosuvastatin
• triptorelin

Mifepristone has moderate interactions with at least 177 different drugs.

Mild interactions of mifepristone include:

• ruxolitinib

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

Mifeprex:

• Serious and sometimes fatal infections and bleeding occur very rarely following spontaneous, surgical, and medical abortions
• Atypical presentation of infection reported; patients with serious bacterial infections (e.g., Clostridium sordellii) and sepsis can present without fever, bacteremia, or significant findings on pelvic examination following an abortion; very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, fast heart rate (tachycardia), hemoconcentration, and general malaise
• Prolonged heavy bleeding may be a sign of incomplete abortion or other complications that requires prompt medical attention
• Should be used only with strict adherence to recommended dosages by medically trained personnel who can provide immediate intensive care in acute surgical facilities

This medication contains mifepristone.

Do not take Mifeprex, Korlym, or RU486 if you are allergic to mifepristone or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Korlym:

• Potent antiprogestational effects and will result in the termination of pregnancy
• Pregnancy must therefore be excluded before the initiation of treatment with Korlym, or if treatment is interrupted for more than 14 days in females of reproductive potential
• Pregnancy must be prevented during treatment and for 1 month after stopping treatment by the use of a nonhormonal medically acceptable method of contraception unless the patient has had a surgical sterilization

Contraindications

Known hypersensitivity to mifepristone, misoprostol, or other prostaglandins

Mifeprex:

• Confirmed or suspected ectopic pregnancy, undiagnosed adnexal mass, or IUD currently in place
• Chronic adrenal failure or concurrent long-term corticosteroid therapy
• Hemorrhagic disorders inherited porphyrias or concurrent anticoagulant therapy

Korlym:

• Pregnancy
• Coadministration with simvastatin or lovastatin and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus)
• Patients requiring systemic corticosteroids for serious medical conditions
• Women with a history of unexplained vaginal bleeding
• Women with endometrial hyperplasia with atypia or endometrial carcinoma

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Mifepristone?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Mifepristone?"

Cautions

Mifeprex

• A clinical examination or ultrasonographic scan should be performed approximately 14 days after mifepristone administration to confirm termination of pregnancy
• Preventive measures to suppress the formation of anti-Rho(D) antibodies (e.g., administration of Rho(D) immune globulin) should be considered in Rho (D)-negative women
• Women who became pregnant with an IUD in place should be assessed for ectopic pregnancy
• Use with caution in women under 35 years who smoke 10 or more cigarettes daily
• Any termination of pregnancy, including those resulting from mifepristone use, may result in serious, potentially fatal infections and bleeding (see Warnings)
• Available only through a restricted program under a REMS called the Mifeprex REMS Program, because of the risks of serious complications; prescribers must be certified and patients must sign a patient agreement form
• Must be dispensed to patients only in certain healthcare settings, specifically clinics, medical offices, and hospitals by or under the supervision of a certified prescriber

Korlym

• Do not use for the treatment of hyperglycemia unrelated to Cushing syndrome
• Adrenal insufficiency may occur; discontinue therapy if signs or symptoms occur and administer glucocorticoids
• Low blood potassium (hypokalemia) should be corrected prior to treatment and monitored for during treatment
• Women may experience endometrial thickening or unexpected vaginal bleeding; use with caution if patient also has a hemorrhagic disorder or is on anticoagulant therapy
• Avoid use with QT interval-prolonging drugs or in patients with potassium channel variants resulting in a long QT interval
• Use of Korlym in patients who receive corticosteroids for other conditions (e.g., autoimmune disorders) may lead to exacerbation or deterioration because of Korlym's glucocorticoid antagonistic effects; for medical conditions in which chronic corticosteroid therapy is life-saving (e.g., immunosuppression in organ transplantation), Korlym is contraindicated
• Coadministration with strong CYP3A inhibitors can increase mifepristone plasma levels significantly; use only when necessary and limit mifepristone dose to 300 mg (see Dosage Modification)

Pregnancy and Lactation

• The Mifeprex brand of mifepristone has no FDA category rating
• It is indicated for use in the termination of pregnancy
• Do not use the Korlym brand of mifepristone in pregnancy
• The risks involved outweigh potential benefits
• Safer alternatives exist
• Due to its antiprogestational activity, it causes pregnancy loss
• Mifepristone is distributed in human milk
• Because of the potential for serious adverse reactions in nursing infants from mifepristone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother