Pharmacology · Antiprogestogens (progesterone receptor modulators)
Mifepristone !
Progesterone receptor blocker used with misoprostol to end an early intrauterine pregnancy or to empty the uterus after fetal death (WHO essential list).
Updated 2026-11-01
Crystal structure of the ligand-binding domain of the human progesterone receptor with mifepristone (RU486) bound.
Mechanism of action
Mifepristone is a steroid that binds the progesterone receptor without activating it. Without progesterone action the decidua breaks down, the cervix softens and the uterus contracts and becomes more sensitive to prostaglandins; misoprostol given afterwards completes the expulsion. It also blocks the glucocorticoid receptor and has weak antiandrogen activity.
- Mifepristone occupies the progesterone receptor and blocks it
- The decidua breaks down and the cervix softens
- The uterus becomes sensitive to prostaglandins
- Misoprostol, given afterwards, causes expulsion
Pharmacokinetics
- Absorption
- By mouth; about 69% bioavailability
- Distribution
- About 98% bound to plasma proteins
- Metabolism
- Liver, mainly through CYP3A4
- Elimination
- Mostly in faeces
- Half-life
- About 18 hours (terminal)
Indications
- Medical termination of an early intrauterine pregnancy, together with misoprostol
- Emptying of the uterus after fetal death, together with misoprostol (WHO essential list) Miscarriage (early pregnancy loss) →
Adverse effects
Common
- Cramping and bleeding heavier than a period (expected)
- Nausea, vomiting and diarrhoea
- Fever or chills, weakness and headache
- Dizziness
Contraindications
- Confirmed or suspected ectopic pregnancy, or an undiagnosed adnexal mass
- Intrauterine device in place (it is removed first)
- Chronic adrenal failure or long-term corticosteroid therapy
- Bleeding disorders or anticoagulant therapy
- Inherited porphyria
- Allergy to mifepristone, misoprostol or other prostaglandins
Key interactions
- CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, dexamethasone, St John's wort)
- Lower mifepristone levels and possible failure
- CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, grapefruit juice)
- Higher mifepristone levels
- Narrow-margin CYP3A4 substrates
- Mifepristone can raise their levels for a long time
- Corticosteroids
- Their effect is blocked at the glucocorticoid receptor
What is monitored
- Ultrasound or clinical assessment beforehand to confirm an intrauterine pregnancy and its duration
- Follow-up to confirm that the pregnancy has ended
- Amount and duration of bleeding; haemoglobin if heavy
- Signs of infection: fever, abdominal pain, fast pulse, even without fever
- Rh status, with the same prevention as after surgical abortion
Administration and safety
- Given by mouth, followed later by misoprostol according to the protocol in use.
- Ectopic pregnancy is excluded and any IUD is removed before use.
- The patient receives clear written instructions on whom to call and when to go to an emergency service.
Nursing care
- Before use: confirm pregnancy location and duration, Rh status, anticoagulants, steroids and adrenal disease.
- Teaching: cramping and bleeding are expected; soaking pads for hours, fainting, fever or severe pain need urgent care.
- Explain that infection can present without fever: weakness, abdominal pain or a fast heart rate also count.
- Arrange follow-up to confirm the outcome.
Pregnancy and breastfeeding
Used only to end an early pregnancy or empty the uterus after fetal death; follow-up confirms the outcome, and an ongoing pregnancy is usually completed with a procedure.
Test yourself
Think of the answer, then tap the question to see it.
Which diagnosis must be excluded before mifepristone is used?
Ectopic pregnancy: mifepristone does not treat it, and a rupture could be missed.
Why is mifepristone contraindicated in chronic adrenal failure?
It also blocks the glucocorticoid receptor and could precipitate adrenal insufficiency.
Which medicine follows mifepristone in the WHO-listed regimen?
Misoprostol, which causes the uterine contractions that complete the expulsion.
Related drugs
Related conditions
← Back to the class: Antiprogestogens (progesterone receptor modulators)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MIFEPRISTONE tablet (DailyMed (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.