Mifepristone: How It Works, Uses, Safety & Side Effects

Mifepristone is a prescription drug that has been studied more than any other medicine in reproductive health, and has been used by over 5 million people in the U.S. since FDA approval in 2000. Its most common use is to terminate a pregnancy before 10 weeks (along with another medication), but it's also used to treat miscarriage, Cushing syndrome, and other hormone-related illnesses (off-label).

Here we provide an overview of how mifepristone works, what it's used for, the FDA-approved protocol, potential side effects and its track record of safety over 20 years. This information is sourced from FDA labels, published research and practice guidelines from the World Health Organisation (WHO) and the American College of Obstetricians and Gynecologists. It shouldn't be used as a substitute for advice from your clinician.

What is mifepristone?

Mifepristone is a prescription drug that blocks the hormone progesterone, essential for pregnancy. The medication was invented in France in the 1980s with code name RU-486 (it's still referred to this way in some older medical literature). The U.S. Food and Drug Administration (FDA) approved it in 2000 to terminate pregnancy up to 49 days, but the FDA approved the drug for 70 days in 2016 after additional safety and efficacy data was collected.

It's included in the World Health Organisation's Model List of Essential Medicines, which lists the most important medicines for a basic health system. It's prescribed only by certified providers in the U.S. and as of 2023 can be dispensed at certified retail and mail-order pharmacies as well as clinics.

How does mifepristone work?

Mifepristone interferes with the progesterone receptors, so progesterone can't act to keep the pregnancy implanted or maintain the lining of the uterus. This causes the lining to break down, and for the pregnancy to separate from the wall of the uterus. With the addition of misoprostol 24-48 hours later, the uterus contracts and the pregnancy is expelled.

Mifepristone is from the group of drugs known as antiprogestins or progesterone receptor modulators. The drug is more potent than progesterone at binding progesterone receptors but doesn't activate them, so they stop sending signals. This is the basis of how mifepristone misoprostol is used for medication abortion and management of early pregnancy loss, according to a 2020 review in the New England Journal of Medicine.

It also inhibits progesterone receptors at higher concentrations, and that's why a different formulation is approved to treat Cushing syndrome, which occurs when someone has an excess of cortisol.

Uses of mifepristone

Mifepristone has one FDA-approved use for pregnancy and one for Cushing syndrome, plus several well-established off-label uses backed by major medical societies.

The mifepristone misoprostol combination is the most common use by a wide margin. ACOG's clinical bulletin notes the same regimen is also first-line treatment for early pregnancy loss, where it helps the body complete a miscarriage at home rather than requiring a procedure.

Mifepristone dosage and regimen

The routine dose of mifepristone for medication abortion or miscarriage is a single 200 mg oral pill, followed 24 to 48 hours later by misoprostol, FDA prescribing information says. The misoprostol part is taken at home, in the cheek or vaginally (as prescribed by the clinician).

The timing and dose of the regimen is determined by your clinician, based on gestational age, medical history and why the medication has been prescribed. They will also provide pain relief and an anti-emetic (against nausea) to be taken with the regimen. You should not take the medication or change the timing without consulting your doctor, as the dose is based on information only your clinician knows for sure, such as your gestational age and ruling out ectopic pregnancy.

Dosing for Cushing syndrome is very different (a pill to take every day long term) and is prescribed by an endocrinologist.

A health app such as August AI can help track symptoms, side effects and bleeding daily to identify any abnormal changes so you know when to reach out to your doctor.

Mifepristone side effects

Common mifepristone side effects when used with misoprostol for pregnancy include cramping, vaginal bleeding, nausea, vomiting, diarrhea, headache, dizziness, fever, and chills. Most fade within 24 hours of taking misoprostol. The cramping and bleeding are how the medication works rather than a sign of complications.

Bleeding heavier than a normal period is expected, and passing clots up to the size of a lemon is normal during the first day. Cramping is often described as stronger than typical menstrual cramps and comes in waves. A heating pad, prescribed pain medication, and rest help most people.

Less common but more serious side effects need medical attention right away:

• Soaking through 2 thick maxi pads per hour for 2 hours in a row

• Fever above 100.4°F lasting more than 24 hours after misoprostol

• Severe abdominal pain not relieved by prescribed pain medication

• No bleeding at all within 24 hours of taking misoprostol

• Signs of allergic reaction (hives, swelling, trouble breathing)

Side effects when mifepristone is used at higher doses for Cushing syndrome are different and include fatigue, low potassium, joint pain, high blood pressure, and changes in thyroid function, which is why ongoing endocrinology follow-up is required.

Mifepristone FDA approval and history

The mifepristone FDA approval timeline stretches across more than two decades of safety review. The drug was approved in September 2000 after clinical trials in the U.S. and Europe involving more than 2,100 women. The original label required in-person dispensing by certified providers.

Three significant updates have followed. In 2016, the FDA extended the approved window from 49 to 70 days of pregnancy and reduced the required dose based on data showing the same effectiveness with fewer side effects. In 2021, the FDA permanently lifted the in-person dispensing requirement during the pandemic after data showed telehealth prescribing was equally safe. In January 2023, the FDA authorized certified retail pharmacies to dispense the medication for the first time.

Each change followed years of safety data review. Through 2022, the FDA's post-marketing surveillance program logged fewer than 1 in 200,000 deaths associated with mifepristone use, which is lower than the rate for many over-the-counter medications including aspirin and acetaminophen.

Mifepristone safety: what the research shows

Mifepristone safety has been studied in dozens of large trials and post-marketing reviews. Serious complications, defined as hospitalization, blood transfusion, or major infection, occur in fewer than 1 in 300 people who take the regimen for early pregnancy, according to a 2022 systematic review in Obstetrics & Gynecology covering more than 30,000 patients.

A few groups should not take mifepristone, or should use it only with extra monitoring:

• People with confirmed or suspected ectopic pregnancy (the medication does not treat ectopic pregnancy and can mask it)

• People with chronic adrenal failure

• People taking long-term corticosteroid therapy

• People with certain bleeding disorders or on anticoagulants

• People with an IUD in place (the IUD must be removed first)

• People with known allergies to mifepristone or misoprostol

The WHO's 2022 abortion care guideline classifies medication abortion with mifepristone-misoprostol as safer than many common outpatient procedures, including wisdom tooth removal and tonsillectomy.

When to call your provider or go to the ER

Most people who take mifepristone complete the process safely without medical contact beyond their planned follow-up. Some symptoms need urgent attention.

Call your provider within 24 hours if you have:

• No bleeding at all within 24 hours of taking misoprostol

• Bleeding lighter than a normal period (could mean the pregnancy continued)

• Fever above 100.4°F lasting more than 24 hours after misoprostol

• Foul-smelling vaginal discharge

• Heavy bleeding lasting more than 2 days at peak

Go to the ER or call 911 for:

• Soaking through 2 or more thick maxi pads per hour for 2 hours

• Severe abdominal pain not relieved by prescribed medication

• Fainting or severe dizziness

• Signs of an allergic reaction (hives, swelling, trouble breathing)

• Heavy bleeding with shoulder tip pain (a possible sign of ectopic pregnancy)

For symptoms that feel off but aren't clear emergencies, August AI lets you describe what you're experiencing in plain language and helps you decide whether to wait, call your provider, or go to the ER. It saves the conversation so you can share it with your clinician later.

Key Takeaways

Mifepristone is a prescription medication that blocks progesterone, used most often with misoprostol to end early pregnancy or manage miscarriage. It's been FDA-approved since 2000, has been used by more than 5 million people in the U.S., and is on the WHO's list of essential medicines. The standard regimen is one 200 mg dose followed by misoprostol 24 to 48 hours later, prescribed by a certified provider.

Common side effects (cramping, bleeding, nausea, headache) usually fade within a day. Serious complications occur in fewer than 1 in 300 cases, making it safer than many outpatient procedures. Heavy bleeding that soaks through 2 pads per hour for 2 hours, fever lasting beyond 24 hours, or severe pain need urgent care. Future fertility is not affected, and generic mifepristone works the same as brand-name versions. State law affects access, so verified directories help confirm options where you live.