RX Patient Tools
Use these quick guides before reading the article, or return to them when you need help preparing questions for a doctor.
Mifepristone is a derivative of the synthetic progestin norethindrone with antiprogesterone activity. Mifepristone competitively binds to the progesterone receptor, resulting in inhibition of the effects of endogenous or exogenous progesterone. This agent also exhibits antiglucocorticoid and weak antiandrogenic activities.
Mifepristone, also known as RU-486, is a potent synthetic steroidal antiprogesterone which is used as a single dose in combination with misoprostol, a prostaglandin analog, to induce a medical abortion. Mifepristone with misoprostol has not been associated with serum enzyme elevations or with clinically apparent liver injury.
Mifepristone alone, without misoprostol, is also approved as therapy of Cushing syndrome where it is given in a higher dose and for extended periods. Long term higher doses of mifepristone have been linked to a low rate of serum enzyme elevations during therapy and rare instances of clinically apparent liver injury.
Mechanism of Action of Mifepristone
The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit, and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing’s syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. Mifepristone competitively inhibits the actions of progesterone at progesterone-receptor sites, resulting in termination of pregnancy. The combination of mifepristone and misoprostol causes expulsion of the products of conception through decidual necrosis, myometrial contractions, and cervical softening.
or
When administered in the early stages of pregnancy, mifepristone causes decidual breakdown by blockade of uterine progesterone receptors. This leads to detachment of the blastocyte, which decreases hCG production. This, in turn, causes a decrease in progesterone secretion from the corpus luteum, which further accentuates decidual breakdown. Decreased endogenous progesterone coupled with blockade of progesterone receptors in the uterus increases prostaglandin levels and sensitizes the myometrium to the contractile actions of prostaglandins.
Indications of Mifepristone
Abortifacient Agents, Steroidal; Contraceptives, Oral, Synthetic; Contraceptives, Postcoital, Synthetic; Hormone Antagonists; Luteolytic Agents; Menstruation-Inducing Agents
- For the medical termination of intrauterine pregnancy through 49 days’ pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.
- Medical termination of developing intra-uterine pregnancy
- Treatment of hypercortisolism (Cushing’s syndrome) of endogenous origin
- Treatment of Cushing’s syndrome secondary to ectopic ACTH secretion
- Treatment of leiomyoma of the uterus
- Mifepristone is indicated in combination with misoprostol for the medical termination of intrauterine pregnancy of 49 days duration or less.
- Mifepristone is indicated in combination with misoprostol for the medical termination of intrauterine pregnancy of 49 days duration or less.
- Mifepristone, also known as RU-486, is a potent synthetic steroidal antiprogesterone which is used as a single dose in combination with misoprostol, a prostaglandin analog, to induce a medical abortion. Mifepristone with misoprostol has not been associated with serum enzyme elevations or with clinically apparent liver injury.
Contraindications of Mifepristone
- severely decreased function of the cortex of adrenal gland
- a sudden decrease in adrenal gland function
- hepatic porphyria
- hereditary liver metabolism disorder
- erythropoietic protoporphyria
- increased risk of bleeding due to a clotting disorder
- high levels of white blood cells
- pregnancy to occur outside of the womb
- abortion complicated by an infection
- pneumonia with a fungus called Pneumocystis
- cancer in the lining of the uterus
- low amount of potassium in the blood
- an increased risk of bleeding
- abnormal EKG with QT changes from birth
- overgrowth of the uterine lining
- are allergic to mifepristone, misoprostol, or any ingredients of the medication
- have an ectopic pregnancy (a pregnancy developing outside of the uterus)
- have an intrauterine device (IUD) in place
- do not know exactly how far you are into your pregnancy
- have chronic adrenal failure
- are taking long-term corticosteroids
- have a bleeding disorder
- are taking medications to prevent blood clots
- have inherited porphyria
- have uncontrolled asthma.
- pregnancy
- Prostaglandins
- Prostaglandins F2a
- Prostaglandins E1
- Prostaglandins E2
Dosage of Mifepristone
Strengths: 200 mg; 300 mg
Abortion
- Day One: 200 mg mifepristone orally as a single dose
- Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).
Post-treatment Assessment Day 7 to 14
- A follow-up visit approximately 7 to 14 days after the administration of mifepristone is necessary to confirm the complete termination of pregnancy and to evaluate the degree of bleeding.
- Termination of pregnancy can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding following treatment usually indicates failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
- The existence of debris in the uterus (e.g., if seen on ultrasonography) following the treatment procedure will not necessarily require surgery for its removal.
- Patients should expect to experience vaginal bleeding or spotting for an average of 9 to 16 days. Heavy bleeding for a median duration of 2 days has been reported. Some women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at the time of follow-up, however, could indicate an incomplete abortion.
- If complete expulsion has not occurred, but the pregnancy is not ongoing, another dose of misoprostol 800 mcg buccally may be administered. A follow-up visit in approximately 7 days to assess for complete termination is recommended.
- Surgical evacuation is recommended to manage ongoing pregnancies after medical abortion.
Cushing’s Syndrome
- Initial dose: 300 mg orally once a day
- Maximum dose: 1200 mg or 20 mg/kg once a day
Pediatric Dose for Abortion
- Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose
- Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).
Side Effects of Mifepristone
The Most Common
- Abdominal or stomach pain or uterine cramping
- pain: Back pain means pain in the spine, muscles, discs, joints, or nerves of the back. সহজ বাংলা: পিঠ/কোমরের ব্যথা।" data-rx-term="back pain" data-rx-definition="Back pain means pain in the spine, muscles, discs, joints, or nerves of the back. সহজ বাংলা: পিঠ/কোমরের ব্যথা।">back pain
- diarrhea
- dizziness
- pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।" data-rx-term="headache" data-rx-definition="Headache means pain in the head or upper neck. সহজ বাংলা: মাথাব্যথা।">headache
- nausea or vomiting
- heartburn
- increased clear or white vaginal discharge
- indigestion
- itching of the vagina or genital area
- lack or loss of strength
- pain during sexual intercourse
- pain or tenderness around the eyes and cheekbones
Common
- hemorrhagic shock (shock from blood loss: dizziness; confusion; rapid breathing and heartbeat; low blood pressure; cool, clammy skin; thirst; dry mouth)
- prolonged heavy vaginal bleeding
- signs of a severe allergic reaction (e.g., itching, rash, hives; swelling of the face, lips, tongue or throat; difficulty breathing or swallowing)
- signs of a severe skin reaction (e.g., skin peeling, especially around mouth and eyes; red spots which burn, itch, or sting; tender red lumps)
- signs of an infection of the uterus lining (e.g., pain in the lower abdomen, fever, and abnormal vaginal discharge)
- signs of infection more than 24 hours after taking misoprostol (e.g., nausea, vomiting, diarrhea or unusual weakness)
- signs of toxic shock syndrome (e.g., fever, diarrhea, nausea, vomiting, muscle aches, low blood pressure, confusion, seizures, red spots or rash that looks like a sunburn)
- worsening asthma symptoms or bronchospasms (e.g., difficulty breathing, coughing, whistling sounds when you breathe, chest tightness).
Rare
- Excessively heavy vaginal bleeding
- unusual tiredness or weakness
- Chest pain or discomfort
- confusion
- cough or hoarseness
- fever or chills
- lower back or side pain
- pain or discomfort in the arms, jaw, back, or neck
- painful or difficult urination
- pale, cold, or clammy skin
- shortness of breath
- a sudden increase in stomach or shoulder pain
- sweating
- an unusual or large amount of vaginal bleeding
Drug Interactions of Mifepristone
- alpha-blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- androgens (e.g., methyltestosterone, nandrolone, testosterone)
- anti-cancer medications (e.g., cabazitaxel, docetaxel; doxorubicin; etoposide, ifosfamide, irinotecan, vincristine)
- antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- birth control pills
- bisoprolol
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- celecoxib
- corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- dantrolene
- diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
- domperidone
- ergot alkaloids (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine)
- estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
- everolimus
- famotidine
- granisetron
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- hydrocodone
- kinase inhibitors (e.g., dasatinib, imatinib, nilotinib)
- lidocaine
- losartan
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- metronidazole
- mirtazapine
- modafinil
- monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
- montelukast
- nilotinib
- nitrates (e.g., isosorbide dinitrate, isosorbide mononitrate)
- ondansetron
- phenobarbital
- phenytoin
- progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- repaglinide
- St. John’s wort
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- sildenafil
- sotalol
- statin anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- sulfamethoxazole
- tacrolimus
- tamoxifen
- tetracycline
- theophylline
- tizanidine
- tolterodine
- tramadol
- trimethoprim
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- vardenafil
- venlafaxine
- warfarin
- zafirlukast
Depending on your specific circumstances, your doctor may want you to
- stop taking one of the medications,
- change one of the medications to another,
- change how you are taking one or both of the medications
Pregnancy Category of Mifepristone
US FDA Pregnancy Category X
Pregnancy
You can become pregnant immediately after using this medication, and this medication may cause harm to a developing baby. To decrease the chance of birth defects, avoid becoming pregnant before your next menstrual period. To avoid becoming pregnant, start using birth control right away.
Lactation
Mifepristone may pass into breast milk. Misoprostol does pass into breast milk. If you are a breast-feeding mother and take mifepristone – misoprostol, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this medication have not been established for children less than 15 years of age.
References
