mifepristone
Mifeprex, RU-486

Available forms

Tablets: 200 mg

Indications and dosages
 Termination of intrauterine pregnancy through 49th day of pregnancy. Adults: On day 1, give 600 mg (three 200-mg tablets) P.O. as a single dose. On day 3, unless abortion is confirmed by clinical examination or ultrasonographic scan, give misoprostol 400 mcg P.O.

Pharmacodynamics
Antiprogestational action: Drug is a synthetic steroid with antiprogestational effects. It competitively interacts with progesterone at progesterone-receptor sites, inhibiting the activity of endogenous and exogenous progesterone, causing termination of pregnancy.

Pharmacokinetics
Absorption: Rapidly absorbed; absolute bioavailability is 69%.
Distribution: Mifepristone is 98% bound to plasma proteins, albumin, and α₁-acid glycoprotein.
Metabolism: Metabolized by N-demethylation and terminal hydroxylation to three major metabolites. In vitro studies have shown that CYP-450 3A4 is primarily responsible for the metabolism.
Excretion: Excreted in the feces and urine. Terminal half-life is 18 hours.

Contraindications and precautions
Contraindicated in patients with confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass, or in patients with an intrauterine device in place. Also contraindicated in patients with chronic adrenal failure, patients on concurrent long-term corticosteroid therapy, and patients with history of allergy to mifepristone, misoprostol, or other prostaglandins. Contraindicated in patients with inherited porphyrias, hemorrhagic disorders, or anticoagulant therapy.
  The treatment procedure is contraindicated in patients without access to a medical facility equipped to provide emergency treatment of incomplete abortion, blood transfusions, and emergency resuscitation during the period from the first visit until discharge from medical care.
 Don’t administer to any patient who may be unable to understand the effects of the treatment procedure or to comply with its regimen.
 Use cautiously in heavy smokers and patients who have CV disease; hypertension; respiratory, renal, or hepatic disease; insulin-dependent diabetes mellitus; or severe anemia. Also use cautiously in women who are older than age 35 and who also smoke 10 or more cigarettes per day because such patients were excluded from clinical trials of mifepristone.

Interactions
Drug-drug. Carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin: May induce metabolism and reduce serum mifepristone levels. Use together cautiously.
Drugs that are CYP 3A4 substrates and have narrow therapeutic ranges (general anesthetics): Increases serum levels and prolongs elimination of these drugs. Use together cautiously.
Erythromycin, itraconazole, ketoconazole: May inhibit metabolism and increase serum mifepristone levels. Use together cautiously.
Drug-herb. St. John’s wort: May induce metabolism and decrease mifepristone levels. Tell patient to use together cautiously.
Drug-food. Grapefruit juice: May inhibit metabolism and increase mifepristone levels. Tell patient to use together cautiously.

Adverse reactions
CNS: headache, dizziness, fatigue, insomnia, fever, asthenia, anxiety, syncope, fainting.
EENT: sinusitis.
GI: abdominal cramping, nausea, vomiting, diarrhea, dyspepsia.
GU: vaginitis, uterine cramping, pelvic pain, uterine hemorrhage, leukorrhea.
Hematologic: anemia.
Musculoskeletal: back pain, leg pain.
Other: rigors, viral infections, ruptured tubal pregnancies, infection.

Effects on lab test results
• May decrease hemoglobin.

Overdose and treatment
No serious adverse reactions were seen with three times the recommended dose of mifepristone.
 If a patient ingests a massive overdose, she should be observed closely for signs of adrenal failure.

Special considerations
 ALERT Don’t confuse mifepristone (Mifeprex) with misoprostol (Cytotec).
• Drug is supplied only to licensed physicians who sign and return a prescriber’s agreement. It isn’t available through pharmacies.
• For purposes of this treatment, pregnancy is dated from the first day of the last menstrual period in a presumed 28-day cycle with ovulation occurring at mid-cycle. The duration of pregnancy may be determined from menstrual history and clinical examination. Ultrasonographic scan should be used if the duration of pregnancy is uncertain, or if ectopic pregnancy is suspected.
• Patient must read the medication guide and sign the patient agreement before drug is given.
• Any intrauterine device must be removed before treatment begins.
• Mifepristone and misoprostol treatment for the termination of pregnancy requires three prescriber office visits by the patient for proper administration. This treatment may be administered only in a clinic, medical office, or hospital, by or under the supervision of a clinician able to assess gestational age and to diagnose ectopic pregnancies. Clinician must also be able to provide surgical intervention in cases of incomplete abortion or severe bleeding, or have made plans to provide such care through others, and be able to ensure patient access to medical facilities equipped to provide blood transfusions and resuscitation, if needed.
• During the period following administration of misoprostol, the patient may need medication for cramps or GI symptoms.
• Patient must return for a follow-up visit about 14 days after administration of mifepristone to determine by clinical examination or ultrasound that a complete termination of pregnancy has occurred and to assess the degree of bleeding. Patients who have an ongoing pregnancy at this visit have a risk of fetal malformation resulting from the treatment. Surgical termination is recommended.
• Vaginal bleeding and uterine or abdominal cramping are expected effects of drug. Vaginal bleeding or spotting occurs for an average of 9 to 16 days. Excessive bleeding may require treatment with vasoconstrictors, curettage, saline infusions, and blood transfusions. Persistence of heavy or moderate bleeding at the 14-day follow-up visit may indicate incomplete abortion.
• Store mifepristone at controlled room temperature.
Breast-feeding patients
• It isn’t known whether mifepristone appears in breast milk. Breast-feeding women may need to discard their breast milk for a few days following administration.

Patient education
• Give patient a copy of the medication guide and the patient agreement. Review them with patient and discuss any questions the patient has.
• Inform patient of the importance of completing the treatment schedule, and stress the need for a follow-up visit about 14 days after taking mifepristone.
• Tell the patient to expect vaginal bleeding that may be heavy at times along with uterine cramping.
• Inform patient that vaginal bleeding isn’t proof of a complete abortion and that she must return for follow-up to confirm the abortion.
• Inform patient that if treatment fails, surgical intervention may be needed.
• Supply patient with a name and telephone number to contact in case of emergency.
• Inform patient that she may become pregnant again as soon as termination of pregnancy is complete and before normal menses has returned.
• Teach the patient about forms of contraception.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use