Mifepristone is a synthetic steroid with potent antiprogestogenic and antiglucocorticoid activity. In the 25mg strength, it is primarily indicated for the medical management of hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. It acts as a competitive antagonist at progesterone and glucocorticoid receptors.
Adult: For Cushing's syndrome: Initially 300 mg once daily (i.e., twelve 25mg tablets). Titrate based on clinical response and tolerability. Maximum recommended dose is 1200 mg (forty-eight 25mg tablets) once daily. Dose adjustments should be made in 300 mg increments.
Note: Administer orally once daily with a meal. Swallow tablets whole with a glass of water. Do not crush, split, or chew. Consistency in timing with respect to meals is recommended. If a dose is missed, it should be taken as soon as remembered on the same day. If missed entirely, the next dose should be taken at the regular time the following day. Do not double the dose.
Mifepristone is a competitive antagonist at the progesterone receptor (PR) and the glucocorticoid receptor (GR). For Cushing's syndrome, its therapeutic effect is primarily due to GR blockade. By binding to the GR with high affinity, it inhibits the effects of cortisol, including its gluconeogenic, anti-inflammatory, and immunosuppressive actions. This leads to improved insulin sensitivity and reduced hyperglycemia.
Pregnancy: CONTRANDICATED. Mifepristone is a potent abortifacient. It may cause fetal death, uterine contractions, and expulsion of the products of conception. Pregnancy must be excluded before initiation and avoided during therapy. Women of childbearing potential must use a non-hormonal, highly effective method of contraception (e.g., copper-T IUD, barrier methods) during and for at least one month after treatment.
Driving: May cause fatigue, dizziness, and blurred vision. Patients should be cautioned about operating machinery or driving until they know how the medication affects them.
| Ketoconazole, Itraconazole, Clarithromycin | Strong CYP3A4 inhibitors increase mifepristone plasma concentrations significantly. Concomitant use is contraindicated. | Major |
| Rifampicin, Carbamazepine, Phenytoin, St. John's Wort | Strong CYP3A4 inducers decrease mifepristone plasma concentrations, reducing efficacy. Avoid concomitant use. | Major |
| Simvastatin, Lovastatin | Mifepristone (a strong CYP3A4 inhibitor at steady-state) increases statin levels, increasing risk of myopathy/rhabdomyolysis. Use lowest possible statin dose or avoid. | Major |
| Midazolam, Triazolam | Increased sedation and prolonged effect due to CYP3A4 inhibition by mifepristone. Avoid or adjust dose. | Moderate |
| Warfarin | Potential for increased INR due to protein binding displacement and CYP inhibition. Monitor INR closely. | Moderate |
| Corticosteroids (e.g., Dexamethasone, Prednisolone) | Mifepristone antagonizes the glucocorticoid effects. Dosage of corticosteroids may need adjustment if used for non-Cushing's indications (e.g., adrenal insufficiency). | Major |
| Fentanyl, Alfentanil | Increased opioid effects and risk of respiratory depression. Monitor closely. | Moderate |
| Digoxin | Mifepristone may increase digoxin serum levels. Monitor digoxin levels. | Moderate |
Same composition (Mifepristone (25mg)), different brands: