Mifepristone Drug Interactions: What to Avoid and What to Tell Your Doctor

Mifepristone has several important drug interactions that patients — and their providers — need to know about before starting treatment. Because mifepristone is metabolized primarily by a liver enzyme called CYP3A4, drugs that affect this enzyme can significantly raise or lower mifepristone levels in the body. Other interactions relate directly to mifepristone's mechanism of action (blocking progesterone and cortisol receptors). This guide covers the most important interactions for both Mifeprex (abortion) and Korlym (Cushing's syndrome) use.

Contraindicated Combinations: Do NOT Use These With Mifepristone

The following drug combinations are contraindicated — meaning they should not be used together with mifepristone because the risk of serious harm is too high:

• Anticoagulants and blood thinners (warfarin, heparin, enoxaparin, apixaban, rivaroxaban, etc.): Mifepristone causes bleeding as part of its mechanism. Combining it with anticoagulants significantly increases the risk of excessive, potentially life-threatening bleeding. This applies to both the abortion and Cushing's uses.
• Aspirin and NSAIDs (ibuprofen, naproxen): Aspirin inhibits platelet function, which can cause excessive post-abortion bleeding when combined with mifepristone. This is particularly important for Mifeprex use. Note: Ibuprofen may be used for pain relief after misoprostol at the provider's recommendation in specific situations — discuss with your prescriber.
• Long-term corticosteroid therapy (prednisone, dexamethasone, budesonide, etc.): Mifepristone blocks the cortisol/glucocorticoid receptor. For patients who depend on corticosteroids for life-sustaining conditions (such as organ transplant immunosuppression, severe asthma, or autoimmune disorders), blocking these receptors can cause their underlying condition to worsen severely. Korlym is contraindicated in patients on long-term systemic corticosteroid therapy.
• Simvastatin and lovastatin (with Korlym): Mifepristone inhibits CYP3A4, causing levels of simvastatin and lovastatin to rise dramatically. This can lead to severe muscle damage (rhabdomyolysis). Korlym should not be used with simvastatin or lovastatin.
• Hormonal contraceptives (with Korlym): Hormonal birth control (pills, patch, ring, implant, injection) is contraindicated with Korlym because mifepristone can interfere with their effectiveness. Women of childbearing potential taking Korlym must use non-hormonal contraception.

Major Interactions: Use With Caution and Medical Supervision

• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, nefazodone): These drugs block the enzyme that breaks down mifepristone, causing mifepristone blood levels to rise significantly. This increases the risk of side effects. If mifepristone must be used with a strong CYP3A4 inhibitor, the dose should be limited (Korlym: max 300 mg/day; per some labeling updates, up to 900 mg/day with monitoring). Avoid this combination if possible.
• Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's Wort): These drugs speed up CYP3A4 activity, causing mifepristone to be broken down much faster. This can reduce mifepristone effectiveness significantly. Rifampin (used for tuberculosis) and anticonvulsants like carbamazepine and phenytoin are common examples. Do not use Korlym with strong CYP3A4 inducers.
• QT-prolonging drugs (certain antiarrhythmics, antipsychotics, antibiotics): Mifepristone (especially Korlym) can prolong the QT interval — a measure of heart electrical activity. Combining it with other QT-prolonging drugs increases the risk of a dangerous heart rhythm called torsades de pointes. Examples include amiodarone, sotalol, haloperidol, methadone, and some fluoroquinolone antibiotics.
• Narrow therapeutic index CYP3A4 substrates (cyclosporine, tacrolimus, fentanyl, sirolimus, pimozide, quinidine): Mifepristone inhibits CYP3A4, which can raise blood levels of drugs that use this enzyme for metabolism. For drugs with a narrow therapeutic window (even small changes in blood level are dangerous), this can be critical. Use the lowest possible doses of these drugs when co-prescribed with Korlym.

Food Interactions

• Grapefruit and grapefruit juice: Grapefruit inhibits CYP3A4 in the intestine, which can significantly raise mifepristone blood levels, especially for Korlym. Avoid grapefruit and grapefruit juice entirely while taking Korlym. This interaction is less concerning for the single-dose Mifeprex regimen but should be disclosed to your provider.

Herbal and Supplement Interactions

• St. John's Wort: A popular herbal supplement for depression, St. John's Wort is a potent CYP3A4 inducer. It can substantially reduce mifepristone blood levels and effectiveness. Do not use St. John's Wort with Korlym.

What to Tell Your Doctor Before Taking Mifepristone

Before taking mifepristone, give your prescriber a complete list of all medications, supplements, and herbal products you take. Specifically mention:

• Any blood thinners or antiplatelet medications (including daily aspirin)
• Any steroids or corticosteroids (prednisone, dexamethasone, inhaled steroids if at high doses)
• Any antifungal medications (ketoconazole, itraconazole, fluconazole)
• Any HIV medications, especially protease inhibitors (ritonavir, lopinavir, atazanavir)
• Any seizure medications (carbamazepine, phenytoin, phenobarbital)
• St. John's Wort or other herbal supplements
• Any heart medications, especially those known to affect heart rhythm

Always disclose your complete medication list — including over-the-counter drugs and supplements — before taking mifepristone. For information on side effects to watch for, see our mifepristone side effects guide. If you're still looking for a pharmacy that can fill your mifepristone prescription, medfinder can help locate certified pharmacies near you.