Skip Navigation

DRUG RECORD

 

MIFEPRISTONE

OVERVIEW
Mifepristone/Misoprostol

 

Introduction

Mifepristone, also known as RU-486, is a potent synthetic steroidal antiprogesterone which is used in combination with misoprostol, a prostaglandin analogue, to induce medical abortion.  Mifepristone with misoprostol have not been associated with serum enzyme elevations or with clinically apparent liver injury.

 

Background

Mifepristone (mif" e pris' tone) is a synthetic antiprogesterone which 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 (mye" soe pros' tol) is 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 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 are 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.  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 (REMS) program to certified prescribers.  Mifepristone (without misoprostol) is also approved for use in Cushing syndrome, caused by excessive production of glucocorticoids.  Mifepristone also has antiglucocorticoid receptor activity and has been found to alleviate symptoms and signs of hypercortisolism.

 

Hepatotoxicity

In large prelicensure clinical trials, medical abortion with mifepristone/misoprostol was safe and not accompanied by abnormalities in laboratory tests or cases of hepatitis or jaundice.  Since its licensure and more widescale use, there have been no published reports of liver injury attributed to mifepristone and misoprostol used to induce medical abortion.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

 

Mechanism of Injury

The mechanism by which mifepristone/misoprostol might cause liver injury is uncertain.  The single dose administration of mifepristone and low doses of misoprostol are reasons why they may not be hepatotoxic.  Mifepristone is metabolized by the liver, largely by the cytochrome P450 isozyme CYP 3A4 and plasma levels vary if inducers or inhibitors of CYP 3A are used concurrently.

 

Drug Class:  Obstetrical and Gynecological Agents, Pregnancy Termination Agents

 

Top of page

 

PRODUCT INFORMATION
Mifepristone/Misoprostol


REPRESENTATIVE TRADE NAMES
Mifepristone – Korlym®, Mifeprex®


DRUG CLASS
Pregnancy Termination Agents


COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

 

Top of page

 

CHEMICAL FORMULAS AND STRUCTURES
Mifepristone/Misoprostol
DRUG CAS REGISTRY NO MOLECULAR FORMULA STRUCTURE
Mifepristone 84371-65-3 C29-H35-N-O2 Mifepristone chemical structure
Misoprostol 59122-46-2 C22-H38-O5 Misoprostol chemical structure

Top of page


REFERENCES
Mifepristone/Misoprostol

 

References updated:  01 April 2017   

  1. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.  (Review of hepatotoxicity published in 1999 before the availability of mifepristone).

  2. Chitturi S, Farrell GC. Estrogen receptor antagonists. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 610-2.  (Review of hepatotoxicity of hormonal agents; does not discuss mifepristone).

  3. Schimmer BP, Parker KL. Contraception and pharmacotherapy of obstetrical and gynecological disorders. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1833-52.  (Textbook of pharmacology and therapeutics).

  4. Couzinet B, Le Strat N, Ulmann A, Baulieu EE, Schaison G. Termination of early pregnancy by the progesterone antagonist RU 486(Mifepristone). N Engl J Med 1986; 315: 1565-70. PubMed Citation  (Among 100 women with an early, unwanted pregnancy who were treated with 1 of 3 regimens of mifepristone [400 to 800 mg total dose], 85 had a complete abortion within 8 days and “the only important side effect observed…was prolonged uterine bleeding”).

  5. Rodger MW, Baird DT. Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. Lancet 1987; 2(8573): 1415-8. PubMed Citation  (Among 100 women requesting abortion early in pregnancy who were given oral mifepristone [400-600 mg] followed in 48 hours by a prostaglandin analog [gemeprost] by vaginal pessary, 95 had a complete abortion and adverse events included bleeding, diarrhea, pelvic pain [after prostaglandin], and incomplete abortion requiring surgical evacuation: “liver function tests” were similar before and after therapy).

  6. Silvestre L, Dubois C, Renault M, Rezvani Y, Baulieu EE, Ulmann A. Voluntary interruption of pregnancy with mifepristone(RU 486) and a prostaglandin analogue. A large-scale French experience. N Engl J Med 1990; 322: 645-8. PubMed Citation  (Among 2040 women given mifepristone followed in 36-48 hours by a prostaglandin analogue [gemeprost pessary or sulprostone intramuscularly], 96% had a complete medical abortion and adverse events included bleeding in almost all women for 1-33 days but not requiring transfusion, abdominal pain in 70-80% with 5-23% requiring analgesics, nausea and diarrhea; no mention of ALT elevations or hepatotoxicity).

  7. Mifepristone(RU 486). Med Lett Drugs Ther 1990; 32 (833): 112-3. PubMed Citation  (Concise review of the mechanism of action, efficacy, and safety of oral mifepristone for induction of medical abortion).

  8. Peyron R, Aubény E, Targosz V, Silvestre L, Renault M, Elkik F, Leclerc P, et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med 1993; 328: 1509-13. PubMed Citation  (Among 873 women in two open label trials of mifepristone and different doses of misoprostol 48 hours later, medical abortion was induced in 96-98% and adverse events included uterine bleeding and cramps, nausea and diarrhea; no mention of ALT elevations or hepatotoxicity).

  9. Cheng L, Che Y, Gülmezoglu AM. Interventions for emergency contraception. Cochrane Database Syst Rev 2012; (8): CD001324. PubMed Citation  (Systematic analysis of 100 randomized controlled trials of emergency contraception with 55,666 women using mifepristone, levonorgestrel, copper intrauterine device placement and ulipristal reported that all regimens were safe; no mention of ALT elevations or hepatotoxicity).

  10. Mifepristone for Cushing's syndrome. Med Lett Drugs Ther 2012; 54 (1392): 46-7. PubMed Citation  (Concise review of the mechanism of action, clinical efficacy, safety and costs of mifepristone for Cushing syndrome shortly after its approval for this indication in the US; does not mention ALT elevations or hepatotoxicity).

  11. Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52. PubMed Citation  (Among 899 cases of drug induced liver injury collected in the United States between 2004 and 2012, no cases were attributed to mifepristone or other emergency contraception regimens).

  12. Mifepristone (Mifeprex) label changes. Med Lett Drugs Ther 2016; 58 (1493): 55-6. PubMed Citation  (Concise summary of changes in dosages of mifepristone [200 mg] and misoprostol [800 mcg] and expansion of indications [use within 70 days after first day of last menstrual period]).

Top of page

 

OTHER REFERENCE LINKS
Mifepristone/Misoprostol
  1. PubMed logoRecent References on Mifepristone/Misoprostol

  2. Clinical Trials logoTrials on Mifepristone/Misoprostol

Top of page