Mifegyne

What Is Mifegyne and What Is It Used For?

Mifegyne is a prescription medication containing mifepristone, an antiprogestogen that blocks the action of progesterone – a hormone essential for maintaining pregnancy. By blocking progesterone, Mifegyne causes the uterine lining to break down, softens the cervix, and increases the uterus’s sensitivity to prostaglandins, ultimately leading to termination of pregnancy when used in combination with a prostaglandin analogue.

Mifepristone was first developed in France in the early 1980s and has been available for clinical use since 1988. It was a landmark development in reproductive medicine, offering a non-surgical alternative for termination of pregnancy. Today, mifepristone is included on the World Health Organization’s Model List of Essential Medicines, recognising its fundamental importance in global reproductive healthcare. It is approved and used in over 60 countries worldwide.

Mifegyne works at the molecular level by competing with progesterone for binding to progesterone receptors in the uterus. Progesterone is critical for maintaining the decidua (the modified uterine lining that supports the embryo) and suppressing uterine contractions during pregnancy. When mifepristone blocks these receptors, several key physiological changes occur: the decidua undergoes necrosis and detachment, the cervix softens and begins to dilate, the myometrium (uterine muscle) becomes more sensitive to prostaglandins, and the embryo separates from the uterine wall.

However, mifepristone alone causes complete expulsion in only about 60–80% of cases. This is why it is almost always used in combination with a prostaglandin analogue (typically misoprostol or gemeprost), which induces powerful uterine contractions that expel the pregnancy. The combination regimen achieves success rates of 95–98% for early medical abortion.

Approved Indications

Mifegyne is recommended for the following clinical uses:

1. Medical termination of intrauterine pregnancy up to 63 days of amenorrhoea. This is the most common use. Mifegyne is taken first, followed 36–48 hours later by a prostaglandin analogue. The combination causes the uterus to contract and expel the pregnancy. For pregnancies up to 49 days, either oral misoprostol (400 micrograms) or vaginal gemeprost (1 mg) may be used. For pregnancies of 50–63 days, vaginal gemeprost (1 mg) is used as the prostaglandin component.

2. Softening and dilation of the cervix before surgical termination in the first trimester. A single tablet of Mifegyne (200 mg) taken 36–48 hours before the procedure makes surgical evacuation easier and reduces the risk of complications such as cervical laceration and uterine perforation.

3. Pre-treatment before prostaglandin administration for termination of pregnancy beyond the first trimester (for medical reasons). Mifegyne sensitises the uterus to the effects of prostaglandins, making the subsequent induction more effective and reducing the total dose and duration of prostaglandin administration required.

4. Induction of labour in cases of intrauterine foetal death. When a foetus has died in the uterus and other medical treatments (prostaglandin or oxytocin alone) are not feasible or have failed, Mifegyne may be used to initiate the process of labour and delivery.

What Should You Know Before Taking Mifegyne?

Before taking Mifegyne, your pregnancy must be confirmed by biological test or ultrasound. You must inform your doctor about all medical conditions, particularly adrenal insufficiency, severe asthma, porphyria, liver or kidney disease, anaemia, cardiovascular conditions, and any blood clotting disorders. Mifegyne is contraindicated in several specific clinical situations.

Contraindications

You must not take Mifegyne in any of the following situations. These apply to all indications:

• Allergy to mifepristone or any of the other ingredients in the tablets (colloidal anhydrous silica, maize starch, povidone, magnesium stearate, microcrystalline cellulose)
• Adrenal insufficiency (adrenal glands do not produce enough hormones) – mifepristone has anti-glucocorticoid properties that could worsen this condition
• Severe asthma that is not adequately controlled with appropriate medication – the prostaglandin component may trigger bronchospasm
• Hereditary porphyria – a group of metabolic disorders affecting haem synthesis that can be exacerbated by mifepristone

Additional contraindications for medical termination up to 63 days:

• Pregnancy not confirmed by biological test or ultrasound
• More than 63 days since the first day of the last menstrual period
• Suspected ectopic pregnancy (the fertilised egg has implanted outside the uterus)
• Inability to take the prescribed prostaglandin

Additional contraindications for cervical softening before surgical abortion:

• Pregnancy not confirmed by biological test or ultrasound
• Suspected ectopic pregnancy
• Gestational age of 84 days or more since the first day of the last menstrual period

Additional contraindications for termination beyond the first trimester:

• Inability to take the prescribed prostaglandin

Warnings and Precautions

Talk to your doctor before taking Mifegyne if you have any of the following conditions, as they may require additional monitoring or precautions:

• Liver or kidney disease – mifepristone is metabolised primarily in the liver, and impaired function may alter drug levels
• Anaemia or malnutrition – the bleeding associated with the abortion process may be poorly tolerated
• Cardiovascular disease – including known heart conditions, or risk factors such as age over 35 years, smoking, high blood pressure, high cholesterol, or diabetes
• Blood coagulation disorders – conditions or medications that affect blood clotting increase the risk of excessive bleeding
• Asthma (even if mild or controlled) – the prostaglandin component may trigger bronchospasm in susceptible individuals

If you have an intrauterine device (IUD or coil), it must be removed before treatment with Mifegyne. Your blood will also be tested for the Rh factor before treatment. If you are Rh-negative, your doctor will arrange appropriate anti-D immunoglobulin prophylaxis to prevent sensitisation.

Pregnancy and Breastfeeding

If the medical abortion fails (the pregnancy continues) after taking Mifegyne alone or in combination with prostaglandin, there is a documented risk of birth defects (particularly limb malformations) if the pregnancy is carried to term. The risk of failed abortion increases if the prostaglandin is not taken as prescribed by your doctor, with advancing gestational age, and with increasing number of previous pregnancies.

If the abortion fails, you have two options. If you decide to continue the pregnancy, you must have careful monitoring throughout, including regular ultrasound examinations (particularly of the limbs) at a specialist centre. Your doctor can provide further information about the potential risks. Alternatively, if you decide you still wish to terminate the pregnancy, a different method will be used. Your doctor will explain the available alternatives.

Breastfeeding: Mifepristone passes into breast milk. You should not breastfeed while taking Mifegyne. Discuss with your doctor when it is safe to resume breastfeeding after treatment is complete.

Fertility: Mifegyne does not affect future fertility. You can become pregnant again as soon as the abortion is complete – ovulation may resume as early as 8–10 days after the procedure. You must begin using a reliable method of contraception immediately once your doctor has confirmed that the pregnancy has been completely terminated.

Driving and Operating Machinery

Dizziness can occur as a side effect of the abortion process itself. Exercise caution if you drive or operate machinery after taking Mifegyne, particularly until you know how the treatment affects you. If you feel dizzy, faint, or unwell, do not drive or operate heavy machinery.

Food and Drink

You must not consume grapefruit juice during treatment with Mifegyne. Grapefruit inhibits the CYP3A4 enzyme responsible for metabolising mifepristone, which can lead to unpredictable changes in blood levels of the medication and potentially alter its effectiveness or increase side effects.

How Does Mifegyne Interact with Other Drugs?

Mifegyne can interact with corticosteroids, certain antifungals, antibiotics, anticonvulsants, herbal supplements, and NSAIDs. Always inform your doctor about all medications you are taking, including over-the-counter products, herbal remedies, and supplements, before starting treatment with Mifegyne.

Mifepristone is primarily metabolised by the liver enzyme CYP3A4. Drugs that inhibit this enzyme can increase mifepristone blood levels, while drugs that induce it can decrease its effectiveness. Additionally, mifepristone itself is a potent inhibitor of CYP3A4, which means it can increase blood levels of other drugs metabolised by this enzyme. The following table summarises the most clinically important interactions.

Major Interactions

Moderate Interactions

Because mifepristone is itself a potent CYP3A4 inhibitor, it can theoretically increase the blood levels of other medications metabolised by this enzyme pathway. This is generally of limited clinical significance because mifepristone is usually administered as a single dose or short course, but it should be kept in mind if you are taking medications with a narrow therapeutic index.

What Is the Correct Dosage of Mifegyne?

The dosage of Mifegyne depends on the indication. For medical abortion up to 63 days, the standard dose is 600 mg (3 tablets) taken orally in a single dose under medical supervision, followed by prostaglandin 36–48 hours later. Mifegyne tablets must be swallowed whole with water and should only be taken in the presence of a healthcare professional.

Always take Mifegyne exactly as your doctor has instructed. The medication is administered in a clinical setting under direct medical supervision. You will not self-administer this medication at home. The dosage varies depending on the specific clinical indication.

Medical Termination up to 49 Days

Medical Termination 50–63 Days

Cervical Preparation Before Surgical Abortion

Termination Beyond the First Trimester

Induction of Labour After Intrauterine Foetal Death

Use in Adolescents

There is limited clinical data on the use of Mifegyne in adolescents. The decision to use mifepristone in this age group should be made on a case-by-case basis by a specialist physician, taking into account the individual clinical circumstances and available alternatives.

Missed Dose

If you forget to take any part of the prescribed treatment, the method may not be fully effective. Contact your doctor or clinic immediately if you miss any dose of the treatment protocol, including the prostaglandin component.

Overdose

What Are the Side Effects of Mifegyne?

The most common side effects of Mifegyne are directly related to the abortion process and include uterine contractions or cramping, nausea, vomiting, and diarrhoea (affecting more than 1 in 10 people). Heavy bleeding and uterine infection are common (up to 1 in 10). Serious but rare side effects include toxic shock syndrome, severe allergic reactions, and serious skin reactions.

Like all medicines, Mifegyne can cause side effects, although not everybody gets them. Many of the side effects listed below are associated with the medical abortion process itself (uterine contractions, bleeding, expulsion) rather than the pharmacological effects of mifepristone alone. The prostaglandin component used in combination contributes significantly to gastrointestinal side effects.

Regarding vaginal bleeding: Vaginal bleeding typically begins 1–2 days after taking Mifegyne and continues for an average of 12 days. In most cases, the bleeding gradually decreases over time. Heavy bleeding (requiring more than 2 pads per hour for 2 consecutive hours) should be reported to your healthcare provider immediately, as it may indicate incomplete abortion or other complications requiring medical intervention.

How Should You Store Mifegyne?

Store Mifegyne in its original packaging to protect from light. No special temperature requirements. Keep out of the reach and sight of children. Do not use after the expiry date printed on the packaging.

Mifegyne does not require any special temperature storage conditions. However, the tablets should be kept in their original packaging (PVC/aluminium perforated unit-dose blister) to protect them from light, as mifepristone is light-sensitive. Check the expiry date (marked “EXP” on the carton and blister) before use. The expiry date refers to the last day of the stated month.

Do not use the medication if the packaging or blister shows signs of damage. Do not flush unused tablets down the drain or throw them in household waste. Return any unused or expired medication to your pharmacy for safe disposal, which protects the environment from pharmaceutical contamination.

In practice, Mifegyne is almost always stored, handled, and dispensed directly by the healthcare facility where the treatment takes place. You will not typically store this medication at home.

What Does Mifegyne Contain?

Each Mifegyne tablet contains 200 mg of the active substance mifepristone. The tablets are light yellow, cylindrical, biconvex, with a diameter of 11 mm and “167 B” engraved on one side.

Active Ingredient

The active substance is mifepristone. Each tablet contains exactly 200 mg of mifepristone. Mifepristone is a synthetic 19-nor steroid compound with potent antiprogesterone and anti-glucocorticoid activity. Its chemical name is 11β-[4-(dimethylamino)phenyl]-17β-hydroxy-17α-(1-propynyl)estra-4,9-dien-3-one.

Inactive Ingredients (Excipients)

The other ingredients are: colloidal anhydrous silica (anti-caking agent), maize starch (filler/binder), povidone (binder), magnesium stearate (lubricant), and microcrystalline cellulose (filler/binder). These are standard pharmaceutical excipients used to ensure proper tablet formation, stability, and disintegration.

Tablet Appearance and Packaging

Appearance: Light yellow, cylindrical, biconvex tablets with a diameter of 11 mm and “167 B” engraved on one side.

Packaging: Available in PVC/aluminium perforated unit-dose blisters in pack sizes of 1, 3 × 1, 15 × 1, or 30 × 1 tablets. Not all pack sizes may be marketed in every country.

Marketing Authorisation Holder

EXELGYN, 216 boulevard Saint-Germain, 75007 Paris, France.

How Does Mifegyne Work in the Body?

Mifepristone is a competitive antagonist of progesterone at the receptor level. By blocking progesterone’s action on the uterus, it causes decidual breakdown, cervical softening, increased uterine sensitivity to prostaglandins, and embryo detachment. The terminal half-life is approximately 25–30 hours.

Progesterone is often called the “pregnancy hormone” because it plays a critical role in establishing and maintaining pregnancy. After ovulation, progesterone prepares the uterine lining (endometrium) for embryo implantation by transforming it into the decidua – a specialised, nutrient-rich tissue that supports the developing embryo. Progesterone also suppresses uterine muscle contractions to prevent premature expulsion and maintains cervical integrity by keeping the cervix firm and closed.

Mifepristone is a synthetic steroid that has a very high affinity for progesterone receptors – approximately five times greater than progesterone itself. When mifepristone binds to these receptors, it effectively blocks progesterone from exerting its effects, even though progesterone levels in the blood remain normal. This competitive antagonism triggers a cascade of events that undermine the conditions necessary for pregnancy to continue.

The primary pharmacological effects of mifepristone on the uterus include:

• Decidual necrosis and detachment: Without progesterone signalling, the decidua breaks down and separates from the uterine wall, depriving the embryo of its blood supply and nutritional support
• Cervical softening and dilation: Mifepristone promotes the release of prostaglandins and other mediators in the cervix, causing it to soften, ripen, and begin to dilate
• Increased myometrial sensitivity: The uterine muscle becomes significantly more sensitive to the contractile effects of prostaglandins, which is why the subsequent administration of a prostaglandin analogue produces powerful uterine contractions
• Embryo detachment: The combination of decidual breakdown and reduced blood supply causes the embryo to separate from the uterine wall

Pharmacokinetic Profile

After oral administration, mifepristone is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations reached within approximately 1–2 hours. The absolute bioavailability is approximately 69%. Mifepristone is highly protein-bound (approximately 98%), primarily to albumin and alpha-1 acid glycoprotein. At high concentrations, mifepristone saturates its binding to alpha-1 acid glycoprotein, leading to non-linear pharmacokinetics.

Mifepristone is extensively metabolised in the liver, primarily by the CYP3A4 enzyme system, through demethylation and hydroxylation reactions. Three main metabolites have been identified, all of which retain some degree of antiprogestogenic activity. The terminal elimination half-life is approximately 25–30 hours. Excretion is primarily via the faeces (83%) with a smaller proportion (9%) excreted in the urine.

Mifepristone also has significant anti-glucocorticoid activity, meaning it can block the effects of cortisol at the glucocorticoid receptor. This is why it is contraindicated in patients with adrenal insufficiency and is the basis for its use in other medical conditions (such as Cushing’s syndrome), although these applications are outside the scope of Mifegyne’s approved indications.

Frequently Asked Questions About Mifegyne