Mifepristone

Mifepristone, commonly known as RU-486, is a potent synthetic antiprogesterone that is primarily used for the medical termination of intrauterine pregnancies, in combination with a prostaglandin analogue, misoprostol. Mifepristone is also approved for the treatment of Cushing syndrome due to its antiglucocorticoid receptor activity.

Pharmacology and Mechanism of Action

Mifepristone acts as a competitive inhibitor of progesterone at the progesterone receptor sites. The subsequent lack of progesterone activity during pregnancy initiates a series of intrauterine and cervical changes that culminate in the termination of pregnancy. The process is completed by the administration of misoprostol, a prostaglandin analogue, which induces uterine contractions.

Clinical Use and FDA Approval

Mifepristone, in conjunction with misoprostol, is approved for the medical termination of intrauterine pregnancies up to 70 days of gestation. Additionally, mifepristone alone is approved for the treatment of hyperglycemia in adults with Cushing syndrome who are not candidates for surgical therapy or have not responded to it. Off-label uses include emergency contraception, although it is not officially approved for this purpose.

Safety and Side Effects

Despite the common occurrence of mild-to-moderate side effects like uterine bleeding, nausea, vomiting, and abdominal cramps, mifepristone is generally considered safe. However, serious adverse events can occur, including severe uterine bleeding, serious bacterial infections, and the failure of abortion leading to the need for hospitalization. Mifepristone has been associated with a low rate of serum enzyme elevations and rare instances of clinically apparent liver injury, particularly when used in higher doses for the long-term treatment of Cushing syndrome.

REMS Program and Contraindications

Due to the severity of potential side effects, the administration of mifepristone and misoprostol is regulated through a Risk Evaluation and Mitigation Strategy (REMS) program, which ensures that prescribers are certified. Contraindications for the use of mifepristone/misoprostol include pregnancy beyond 70 days, ectopic pregnancy, presence of an intrauterine device, adrenal failure, porphyria, and use of anticoagulants.

Brands and Administration

Mifepristone is available in 200 mg tablets under the brand name Mifeprex for the termination of pregnancy, and in 300 mg tablets under the brand name Korlym for the treatment of Cushing syndrome. The recommended dose for inducing medical abortion is a single 200 mg tablet of mifepristone followed 24 to 48 hours later by the buccal administration of 800 mcg of misoprostol. For the treatment of Cushing syndrome, the recommended starting dose of mifepristone is 300 mg once daily, which can be increased based on efficacy and tolerance up to a maximum of 1200 mg daily.

Drug Interactions

Mifepristone is metabolized by cytochrome P450 enzymes CYP 3A4 and 2C8/2C9, resulting in potential drug-drug interactions with medications that inhibit or induce these enzymes. Therefore, concomitant use with other medications metabolized by these enzymes should be approached with caution.

Conclusion

Mifepristone, in combination with misoprostol, is an effective option for medical termination of early intrauterine pregnancy. It is also used for the treatment of Cushing syndrome. Despite its common side effects, with proper management and administration, mifepristone is a critical component of reproductive health.

See also

• Misoprostol
• Abortion
• Emergency contraception
• Cushing syndrome
• Progesterone
• Cytochrome P450

References

Mifepristone Resources
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