Mifeston200 mg

Mifeston is a progesterone receptor antagonist with two distinct, approved indications that use different strengths and dosing regimens:

1. Medical Termination of Early Intrauterine Pregnancy (established, guideline-supported combination therapy)

Mifeston (200 mg) is indicated, in a regimen together with misoprostol, for medical termination of an intrauterine pregnancy through 70 days (10 weeks) of gestation, calculated from the first day of the last menstrual period. Mifeston alone is not adequate for reliable termination and must be followed by misoprostol as directed within an approved protocol.

2. Hyperglycemia in Cushing's Syndrome (established, separate indication)

Mifeston (300 mg strength) is 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. This indication uses a markedly different, chronic daily-dosing regimen and is unrelated to the pregnancy-termination use.

Off-label / other use

Use of Mifeston for menstrual regulation or early pregnancy management outside approved combination regimens and outside licensed, monitored programs is not recommended; it should be used only under direct medical supervision within an approved protocol.

Each tablet contains Mifepristone INN 200 mg (used together with misoprostol for pregnancy termination) or Mifepristone INN 300 mg (used alone for Cushing's syndrome-related hyperglycemia), depending on the approved product and intended indication. Inactive excipients vary by manufacturer.

Mifeston is a synthetic steroid that acts as a competitive antagonist at the progesterone receptor and, at higher doses, also has antiglucocorticoid activity. It is used clinically for two unrelated purposes: as part of a combination regimen with misoprostol for medical termination of early pregnancy, and as standalone therapy to control hyperglycemia associated with endogenous Cushing's syndrome. Because the two indications use different strengths, dosing schedules, and monitoring requirements, Mifeston must always be prescribed and dispensed according to the specific approved regimen for the intended indication, under direct medical supervision.

Progesterone receptor antagonist (antiprogestin); at the higher dose used for Cushing's syndrome, Mifeston also exhibits antiglucocorticoid (glucocorticoid receptor antagonist) activity.

Mifepristone binds competitively to the progesterone receptor, blocking the action of endogenous progesterone. In pregnancy, this leads to trophoblast detachment, decidual breakdown, cervical softening and dilation, and increased uterine sensitivity to prostaglandins - effects completed by subsequent administration of misoprostol.

At the higher dose used for Cushing's syndrome, Mifepristone additionally blocks glucocorticoid receptors, reducing the peripheral effects of excess cortisol and improving glycemic control, without lowering cortisol production itself.

Mifeston tablets are taken by mouth. For the pregnancy-termination regimen, the tablet is swallowed as a single dose under medical supervision, without regard to food. For the Cushing's syndrome regimen, tablets are taken once daily with a meal to reduce gastrointestinal upset. Do not split, crush, or chew the tablets unless specifically directed by a physician.

Mifeston is metabolized by CYP3A4 and has clinically significant interactions with several drug classes:

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, certain HIV protease inhibitors): increase Mifeston plasma concentrations and may increase the risk of adverse effects; avoid or use with caution.
• Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort): reduce Mifeston efficacy; avoid concurrent use.
• Corticosteroids: Mifeston antagonizes glucocorticoid receptors and can reduce the effectiveness of systemic corticosteroids; concurrent long-term corticosteroid use is contraindicated for the pregnancy-termination indication (see Contraindications).
• Sensitive CYP3A4 substrates with narrow therapeutic index (e.g., certain statins, QT-prolonging drugs): increased risk of toxicity; dose adjustment or avoidance may be needed.
• Anticoagulants: increased bleeding risk when combined with Mifeston in the pregnancy-termination regimen; see Contraindications.

Common effects with the pregnancy-termination regimen include vaginal bleeding/spotting (an expected effect), uterine cramping, nausea, vomiting, diarrhea, headache, dizziness, and fever/chills. With the Cushing's syndrome regimen, common effects include fatigue, nausea, headache, low blood potassium, joint pain, vomiting, peripheral swelling, and endometrial thickening or abnormal vaginal bleeding due to the antiprogestin effect.

Serious but less common effects include heavy or prolonged vaginal bleeding, infection, and incomplete termination requiring further intervention. Seek urgent medical care for heavy bleeding, fever lasting more than 24 hours, severe abdominal pain, or signs of infection after taking Mifeston.

Mifeston is used specifically to terminate an existing pregnancy and must never be used if continuation of the pregnancy is intended, given its mechanism of action; if treatment fails to terminate the pregnancy, continuation carries a risk of fetal malformation, so a follow-up visit is essential to confirm complete termination or arrange further management. For the Cushing's syndrome indication, Mifeston should not be used in pregnant women because it can terminate the pregnancy; effective contraception is required during treatment.

Limited data exist on transfer of Mifeston into human breast milk. Use during breastfeeding should be avoided if possible; if use is judged necessary, it should occur only under direct medical supervision, after consultation with a physician who has weighed potential risks against benefits.

Boxed warning: Serious and, rarely, fatal infections and excessive bleeding have occurred following use of Mifeston for pregnancy termination. Patients must be able to reach a physician or emergency medical care without delay throughout the treatment period.

• Mifeston for pregnancy termination is subject to restricted-distribution requirements (REMS-type programs) in many regulatory settings and must be dispensed and administered only by, or under the direct supervision of, a certified prescriber - not through routine retail pharmacy dispensing.
• Follow-up assessment is required approximately 7-14 days after treatment to confirm complete termination; persistent pregnancy or incomplete abortion requires further medical management, which may include surgical evacuation.
• Vaginal bleeding and spotting are expected after use, but bleeding heavier than a normal period for more than 2-3 hours, or that does not slow down, requires urgent medical evaluation.
• Ectopic pregnancy must be ruled out before use, and an in-place IUD must be removed first.
• For the Cushing's syndrome regimen, monitor for low potassium, endometrial changes or abnormal vaginal bleeding, symptoms of adrenal insufficiency (especially during illness, stress, or after stopping treatment), and QT-prolongation risk.
• Dosing and regimens differ substantially between the pregnancy-termination and Cushing's syndrome indications; never interchange doses or schedules between the two uses.

Limited data exist on overdose with Mifeston. In case of suspected overdose, seek immediate medical attention or contact emergency services or a poison control center. Supportive care and close monitoring for excessive bleeding, symptoms of adrenal insufficiency, or other adverse effects should be provided in a medical facility; there is no specific antidote.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Hepatic impairment: Use Mifeston with caution in patients with hepatic impairment, as it is extensively metabolized by the liver; dose adjustment or avoidance may be needed in severe impairment.

Renal impairment: Limited data exist; use with caution and physician oversight.

Elderly: The pregnancy-termination indication does not apply to this population; for the Cushing's syndrome indication, use with caution and monitor closely for adverse effects.

Adrenal insufficiency: Contraindicated in chronic adrenal failure (see Contraindications); use extreme caution and specialist monitoring in other patients at risk, since Mifeston can mask signs of cortisol activity.

For medical termination of pregnancy, Mifeston treatment is a short, defined course: a single oral dose followed by misoprostol 24-48 hours later, with a follow-up visit 7-14 days later to confirm completion. For Cushing's syndrome-related hyperglycemia, Mifeston is typically continued as chronic, ongoing daily therapy for as long as clinically indicated, under regular physician review.

Antiprogestins; progesterone receptor modulators/antagonists; at higher doses, a steroidal antiglucocorticoid agent. Mifepristone is the prototype agent of this class.

Mifepristone competitively blocks progesterone receptors, interrupting the hormonal support needed to sustain early pregnancy and sensitizing the uterus to prostaglandins such as misoprostol, resulting in trophoblast detachment, cervical ripening, and uterine contractions. At higher doses, it also antagonizes glucocorticoid receptors, blunting the peripheral effects of excess cortisol in Cushing's syndrome without reducing cortisol levels themselves.

X

For pregnancy termination, Mifeston follows the same adult regimen in adolescents of reproductive age who are pregnant, but it has no role in prepubertal children. For the Cushing's syndrome indication, safety and efficacy of Mifeston have not been established in pediatric patients; use in children should be avoided outside specialist supervision unless no alternative exists.