mifepristone

Action and Spectrum

Actions and spectrum: 

mifepristone, also known as RU-486, is a medication used for medical abortion and emergency contraception. It acts as a progesterone receptor antagonist, blocking the effects of progesterone, a hormone necessary for the maintenance of pregnancy.

By inhibiting progesterone, mifepristone leads to the breakdown of the uterine lining and the detachment of the embryo, resulting in the termination of pregnancy.

It is effective up to a certain gestational age and is often used in combination with a prostaglandin (e.g., misoprostol) to induce uterine contractions and complete the abortion process. mifepristone is not suitable for terminating ectopic pregnancies or pregnancies past a certain stage, and its use should be under medical supervision. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% (Korlym) 

Fatigue (48%) 

Headache (44%) 

Hypokalemia (34%) 

Vomiting (26%) 

Hypertension (24%) 

Decreased appetite (20%) 

Xerostomia (18%) 

Dyspnea (16%) 

Pain (14%) 

Nasopharyngitis (12%) 

Diarrhea (12%) 

Nausea (48%) 

Endometrial hypertrophy (38%) 

Arthralgia (30%) 

Peripheral edema (26%) 

Dizziness (22%) 

Abnormal thyroid test (18%) 

Back pain (16%) 

Myalgia (14%) 

Sinusitis (14%) 

Extremity pain (12%)  

>10% (Mifeprex) 

Uterine cramping (83%) 

Headache (2-31%) 

Diarrhea (12-20%) 

Abdominal pain, cramping (96%) 

Nausea (43-61%) 

Vomiting (1-26%) 

Dizziness (1-12%)  

1-10% (Mifeprex) 

Back pain (9%) 

Uterine hemorrhage (5%) 

Dyspepsia (3%) 

Rigors (3%) 

Anemia (2%) 

Fainting (2%) 

Leukorrhea (2%) 

Sinusitis (2%) 

Fatigue (10%) 

Decreased hemoglobin (6%) 

Viral infection (4%) 

Insomnia (3%) 

Vaginitis (3%) 

Anxiety (2%) 

Leg pain (2%) 

Pelvic pain (2%) 

Weakness (2%)  

1-10% (Korlym) 

Somnolence (10%) 

Anxiety (10%) 

Abdominal pain (5-10%) 

Hypoglycemia (5-10%) 

Vaginal hemorrhage, metrorrhagia (5-10%) 

Musculoskeletal & connective tissue disorders: flank pain, muscular weakness, musculoskeletal chest pain (5-10%) 

Rash (4%) 

Constipation (10%) 

Anorexia (10%) 

Gastroesophageal reflux (5-10%) 

Increased triglycerides (5-10%) 

Insomnia (5-10%) 

General disorders: malaise, asthenia, pitting edema, edema, thirst (5-10%) 

Adrenal insufficiency (4%) 

Pruritus (4%)  

Post marketing reports 

Angioedema 

Black Box Warning

Black Box Warning: 

mifepristone carries a black box warning due to the risk of serious & potentially life-threatening adverse effects, such as heavy bleeding, infection, and incomplete abortion.

It should only be used under the supervision of a qualified healthcare provider in a medical facility equipped to manage complications. Pregnant women should be aware of potential risks & side effects before using this medication. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Ectopic pregnancy: mifepristone is not suitable for terminating pregnancies outside the uterus. 
• Chronic adrenal failure: Patients with adrenal insufficiency should avoid using mifepristone. 
• Anticoagulant therapy: Concurrent use with anticoagulant medications may increase the risk of bleeding. 
• Inherited porphyria: mifepristone may trigger or worsen this genetic disorder. 
• Known allergy: Individuals with hypersensitivity to mifepristone or its components should avoid its use.

Caution: 

• Bleeding disorders: Patients with bleeding disorders or receiving anticoagulant therapy may experience increased bleeding with mifepristone use. 
• Uterine surgery: Prior uterine surgery may increase the risk of adverse effects or reduce the efficacy of mifepristone. 
• Chronic medical conditions: Patients with heart, liver, or kidney diseases, should be closely monitored during mifepristone treatment. 
• Concurrent medications: mifepristone may interact with certain medications, including corticosteroids and certain anticoagulants. 
• Allergic reactions: Individuals with a history of allergies or sensitivity to mifepristone or related drugs should be cautious while using it.

Comorbidities: 

• Ectopic pregnancy: mifepristone is not effective in terminating ectopic pregnancies and is contraindicated in such cases. 
• Adrenal failure: Patients with adrenal failure or long-term corticosteroid therapy may have altered responses to mifepristone. 
• Hemorrhagic disorders: Individuals with bleeding disorders may experience increased bleeding after mifepristone administration. 
• Severe anemia: mifepristone use may worsen severe anemia in certain cases. 
• Chronic medical conditions: Patients with heart, liver, or kidney diseases, may require special consideration and monitoring during mifepristone treatment. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: X 

Lactation: Excreted into human milk: Yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

mifepristone, also known as RU-486, is a synthetic steroid with a complex pharmacology. It acts as a progesterone receptor antagonist, which means it competitively binds to progesterone receptors and blocks the action of progesterone, a hormone crucial for maintaining pregnancy.

By inhibiting progesterone’s function, mifepristone causes the breakdown of the uterine lining and the detachment of the implanted embryo, leading to pregnancy termination. 

Additionally, mifepristone has glucocorticoid receptor antagonist activity, which can interfere with the action of corticosteroid hormones. This property is utilized in some cases to manage certain medical conditions, such as hypercortisolism (Cushing’s syndrome).  

Pharmacodynamics: 

• Pregnancy Termination: By inhibiting progesterone’s action, mifepristone causes the detachment of the implanted embryo from the uterine lining, leading to its expulsion. This results in medical abortion during the early stages of pregnancy. 
• Cervical Softening and Uterine Contractions: mifepristone causes cervical softening and dilation, preparing the cervix for the subsequent administration of a prostaglandin analogue like misoprostol. The combination of mifepristone and misoprostol enhances uterine contractions, facilitating the expulsion of the pregnancy. 
• Glucocorticoid Receptor Antagonism: mifepristone also acts as a glucocorticoid receptor antagonist, blocking the binding of cortisol and other corticosteroids to their receptors. This property can be utilized in managing conditions like hypercortisolism (Cushing’s syndrome). 

Pharmacokinetics: 

Absorption 

mifepristone is usually administered orally. After ingestion, it is absorbed from the gastrointestinal tract and enters the bloodstream. Food intake can influence its absorption, and therefore, it is often recommended to take mifepristone with a meal. 

Distribution 

mifepristone is extensively distributed throughout the body. It crosses the placenta and can reach the fetal tissues during pregnancy. 

Metabolism 

mifepristone undergoes extensive hepatic metabolism, primarily through the cytochrome P450 enzyme system, particularly CYP3A4. The main metabolites include 11β-hydroxy-mifepristone and 11β-nor-mifepristone, which are less active than the parent compound. 

Elimination and excretion 

mifepristone and its metabolites are primarily eliminated in the feces (approximately 83%) and to a lesser extent in the urine (approximately 9%). 

Adminstartion

Administration: 

• Dosage: The standard dosage for medical abortion with mifepristone is usually a single oral dose of 200 mg. 
• Timing: mifepristone is usually taken during the early stages of pregnancy, up to 70 days (10 weeks) after the first day of the last menstrual period. 
• Follow-up: After taking mifepristone, a follow-up visit to the healthcare provider is essential to monitor the effectiveness of the medication and to plan for the next steps in the abortion process. 
• Misoprostol: In combination with mifepristone, a prostaglandin medication called Misoprostol is usually administered either on the same day or within 1 to 2 days after taking mifepristone to complete the medical abortion process. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mifepristone 

Pronounced: (my-fuh-PRIS-tone)  

Why do we use mifepristone? 

• Medical Abortion: mifepristone, when used in combination with Misoprostol, is prescribed for the termination of early pregnancy, up to 70 days (10 weeks) after the first day of the last menstrual period. 
• Emergency Contraception: mifepristone can be used as an emergency contraceptive if taken within 72 hours after unprotected sexual intercourse. 
• Cushing’s Syndrome: mifepristone is used to treat hyperglycemia (high blood sugar) caused by Cushing’s syndrome, a hormonal disorder resulting from excessive cortisol production. 
• Pregnancy Management: In some cases, mifepristone is used for the cervical ripening & labor induction in pregnancies with fetal death or when termination is medically necessary. 
• Management of Endometriosis: mifepristone can be used to manage symptoms of endometriosis, a condition where the tissue of uterus lining grows outside the uterus. 
• Antiglucocorticoid Effects: mifepristone is sometimes used to treat conditions characterized by excessive cortisol activity, such as psychotic depression and certain types of psychiatric disorders.