When Can Mifepristone Be Used?
Mifepristone is primarily used for medication abortion from early pregnancy through 27 6/7 weeks of gestation (in combination with misoprostol), and is FDA-approved for treating hyperglycemia secondary to Cushing's syndrome in adults with type 2 diabetes or glucose intolerance. 1, 2
Primary Indications
Medication Abortion (14 0/7 to 27 6/7 Weeks Gestation)
Mifepristone 200 mg followed by misoprostol is the most effective regimen for medication abortion between 14 0/7 and 27 6/7 weeks of gestation. 1 This combination regimen demonstrates:
- Lower ongoing pregnancy rates compared to misoprostol alone: 4% vs 32% at 24 hours and 2% vs 10% at 48 hours
- Shorter abortion times: mean 5.8-8 hours with combination vs 11-12 hours with misoprostol alone
- Higher success rates across all gestational ages in this range 1
The standard protocol involves mifepristone 200 mg orally, followed 24-48 hours later by misoprostol 400 mcg (sublingual, buccal, or vaginal routes) every 3 hours. 1
Early First-Trimester Abortion (Up to 63-77 Days Gestation)
Mifepristone 200 mg followed by misoprostol 800 mcg vaginally is effective for early pregnancy termination, with success rates of:
The 24-48 hour interval between medications is critical—concurrent administration significantly reduces efficacy (68.8% vs 84.3% success) and should not be used. 5
Early Pregnancy Loss Management
Mifepristone 200 mg followed by misoprostol 800 mcg (buccal or vaginal) is safe and effective for outpatient management of early pregnancy loss up to 84 days' gestation. 4
Cushing's Syndrome (FDA-Approved)
Mifepristone is FDA-approved to control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes or glucose intolerance and have failed surgery or are not surgical candidates. 2
- Starting dose: 300 mg orally once daily with food
- Maximum dose: 1200 mg daily (not exceeding 20 mg/kg/day)
- Titrate in 300 mg increments every 2-4 weeks based on clinical response 2
Off-Label Uses (Research-Supported)
Emergency Contraception
Mifepristone 10-25 mg as a single dose within 120 hours of unprotected intercourse prevents approximately 85-86% of anticipated pregnancies, with earlier administration being more effective. 6
"Once-a-Month" Contraception
A single 200 mg dose given in the immediate preovulatory phase (within 24 hours of ovulation) prevents implantation without significant menstrual cycle disruption. 7
Other Gynecologic Uses
Research supports potential use for labor induction, ectopic pregnancy treatment, abnormal uterine bleeding, and as adjunct therapy in gynecologic cancers, though these remain investigational. 8
Critical Contraindications
Mifepristone is absolutely contraindicated in: 2
- Pregnancy (when used for Cushing's syndrome—requires negative pregnancy test before initiation)
- Concurrent use with CYP3A substrates with narrow therapeutic ranges (cyclosporine, tacrolimus, sirolimus, pimozide, quinidine, fentanyl, ergotamines)
- Patients on systemic corticosteroids for life-saving purposes (e.g., post-transplant immunosuppression)
- Unexplained vaginal bleeding, endometrial hyperplasia with atypia, or endometrial carcinoma
- Known hypersensitivity to mifepristone
Important Clinical Considerations
Dosing Adjustments
- Renal impairment: Maximum 600 mg daily 2
- Hepatic impairment: Maximum 600 mg for mild-moderate; contraindicated in severe hepatic impairment 2
- Strong CYP3A inhibitors: Reduce mifepristone dose or start at lower doses 2
Safety Profile for Abortion Use
Mifepristone is not teratogenic based on human data—pregnancies that continue after mifepristone exposure without misoprostol do not show increased congenital anomalies. 9 However, the medication is intended to terminate pregnancy, not continue it.
Common Pitfalls to Avoid
- Do not use concurrent administration of mifepristone and misoprostol for early abortion—the 24-48 hour interval is essential for efficacy 5
- Do not rely on serum cortisol levels to assess adrenal insufficiency in Cushing's patients on mifepristone—cortisol remains elevated despite receptor blockade 2
- Do not use for type 2 diabetes unless it is secondary to Cushing's syndrome 2