What is the use of Mifepristone (RU-486)?

From the Guidelines

Mifepristone is effective in controlling bleeding and improving patient quality of life in uterine fibroids, although it does not have a formal indication for this use in any jurisdiction. The medication works by acting on progesterone receptors throughout the reproductive system, inducing several effects that assist in bleeding control and fibroid shrinkage, including direct antiproliferative and pro-apoptotic effects on leiomyoma cells, endometrial changes that reduce bleeding, and inhibition of the pituitary gland’s luteinizing hormone surge, resulting in anovulation and subsequent amenorrhea 1.

Key Points

• Mifepristone has been studied in randomized trials against placebo and leuprolide acetate at doses from 5-50 mg per day, with a Cochrane Review concluding that it is effective at controlling bleeding and improving patient quality of life in uterine fibroids 1.
• The medication has been shown to be effective for improving quality of life, decreasing menstrual blood loss, and achieving amenorrhea, although its clinical development was halted in 2007 due to a change in priorities by its developer 1.
• Other selective progesterone receptor modulators (SPRMs) have been studied in uterine fibroids, including asoprisnil, telapristone acetate, vilaprisan, and ulipristal acetate (UPA), with UPA being superior to placebo for rate of amenorrhea and time to amenorrhea 1.
• Mifepristone is also used for other gynecological conditions like Cushing's syndrome, with guidelines recommending its use cautiously in patients with a history of bipolar or impulse control disorder, and considering drug-drug interactions and concomitant comorbidities such as T2DM and hypertension 1.

Recommendations

• Mifepristone should be considered as an option for the management of uterine fibroids, particularly in patients who are seeking to improve their quality of life and control bleeding.
• Patients should be counseled on the potential side effects of mifepristone, including nausea, vomiting, diarrhea, headache, and dizziness, and should seek immediate medical attention if they experience excessive bleeding, severe pain, fever, or signs of infection after taking the medication.
• The dosage of mifepristone for uterine fibroids is typically in the range of 5-50 mg per day, although the optimal dosage and duration of treatment have not been established.

From the FDA Drug Label

Mifepristone is a potent antagonist of progesterone and cortisol via the progesterone and glucocorticoid (GR-II) receptors, respectively. The antiprogestational effects will result in the termination of pregnancy Pregnancy must therefore be excluded before the initiation of treatment with mifepristone and prevented during treatment and for one month after stopping treatment by the use of a non-hormonal medically acceptable method of contraception Mifepristone is a cortisol receptor blocker indicated to control 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

Mifepristone is used for two main purposes:

• Termination of pregnancy due to its antiprogestational effects
• Control of hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome 2 Key points to consider when using mifepristone include:
• Pregnancy exclusion before initiation of treatment
• Contraception during treatment and for one month after stopping treatment
• Dosage and administration guidelines, including starting dose, titration, and maximum dose limits
• Monitoring for adverse reactions and adjustments to dose as needed

From the Research

Mifepristone Overview

• Mifepristone is a progesterone receptor antagonist used in combination with misoprostol for early pregnancy loss and medication abortion 3, 4, 5, 6.
• The most effective regimens for medication management of early pregnancy loss and medication abortion include 200 mg of oral mifepristone followed by 800 mcg of misoprostol administered buccally or vaginally 3, 4.

Efficacy and Safety

• Medication regimens using mifepristone and misoprostol are safe and effective for outpatient treatment of early pregnancy loss for up to 84 days' gestation and for medication abortion up to 77 days' gestation 3.
• Early medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe, with a complete abortion rate of 98.3% in one study 5.
• The risk of medical abortion failure is higher among trial groups in which at least 25% of subjects have gestational age >8 weeks, the specified interval between mifepristone and misoprostol is less than 24 h, the total misoprostol dose is 400 mcg, or the misoprostol is administered by the oral route 4.

Administration and Side Effects

• Mifepristone can be administered orally, followed by misoprostol administered buccally, vaginally, or sublingually 3, 4, 5.
• Cramping and bleeding are expected effects of the medications, with bleeding lasting an average of nine to 16 days 3.
• Adverse effects of misoprostol, such as low-grade fever and gastrointestinal symptoms, can be managed with nonsteroidal anti-inflammatory drugs or antiemetics 3.

Alternative Regimens

• Misoprostol-only regimens are also effective for medication abortion, with an updated regimen of 800 μg of misoprostol administered buccally, sublingually, or vaginally every 3 hours for three or more doses 7.
• A lower mifepristone dose of 200 mg and in-home self-administration of misoprostol both appear safe and effective 6.