Mifepristone


Generic Medicine Info
Indications and Dosage
Oral
Cushing's syndrome
Adult: To control hyperglycaemia in patients w/ type 2 DM or glucose intolerance: Initially, 300 mg once daily, may increase in increments of 300 mg at 2-4 wk intervals. Max: 1.2 g once daily (but not more than 20 mg/kg daily). Patients taking strong CYP3A4 inhibitors: Max: 300 mg daily.

Oral
Termination of pregnancy (49 days or less duration)
Adult: 600 mg as a single dose, followed by a prostaglandin (either misoprostol 400 mcg orally or gemeprost 1 mg vaginally) 36-48 hr later. Alternatively, 200 mg as a single dose, followed by gemeprost 1 mg vaginally 36-48 hr later.

Oral
Softening and dilatation of cervix prior to surgical termination of pregnancy
Adult: 200 mg as a single dose given 36-48 hr prior to the procedure.

Oral
Termination of pregnancy between 13-24 wk of gestation
Adult: As adjunct to prostaglandin: 600 mg as a single dose given 36-48 hr prior to prostaglandin therapy.

Oral
Induction of labour following intrauterine fetal death
Adult: 600 mg daily for 2 consecutive days.

Oral
Termination of pregnancy up to 63 days
Adult: 600 mg as a single dose followed by 1 mg gemeprost vaginally 36-48 hr later.
Renal Impairment
Cushing’s syndrome: Max: 600 mg daily.
Hepatic Impairment
Cushing’s syndrome: Mild to moderate: Max: 600 mg daily. Severe: Avoid.
Administration
May be taken with or without food. Avoid grapefruit juice.
Contraindications
Termination of pregnancy: Confirmed or suspected ectopic pregnancy, undiagnosed adnexal mass, chronic adrenal failure, porphyria, haemorrhagic disorder. Concurrent anticoagulant therapy. Cushing’s syndrome: Women w/ history of vag bleeding, endometrial hyperplasia w/ atypia or endometrial carcinoma. Pregnancy. Concomitant use w/ lovastatin, simvastatin and CYP3A4 substrates w/ narrow therapeutic range. Concurrent long-term corticosteroid use for serious medical conditions.
Special Precautions
Patient w/ haemostatic disorders or anaemia; malnutrition. Patients taking strong CYP3A4 inhibitors (when used in the treatment of Cushing’s syndrome). Hepatic and renal impairment. Lactation.
Adverse Reactions
Uterine bleeding and cramps, chills, fever, malaise, dizziness, headache, diarrhoea, nausea, vomiting, urticaria, rash; hypokalaemia, GI disturbances, decreased appetite, drowsiness, fatigue, dyspnoea, anxiety, peripheral oedema, HTN, arthralgia, myalgia, back pain, endometrial thickening, cystic dilatation of endometrial glands, adrenal insufficiency, prolonged QT interval.
Potentially Fatal: Serious infections.
Monitoring Parameters
Termination of pregnancy: Monitor Hb, haematocrit and RBC count in cases of heavy bleeding; CBC in patients who show signs of infection. Conduct clinical exam and/or ultrasound to confirm complete termination of pregnancy. Cushing’s syndrome: Monitor thyroid function, serum glucose, psychiatric symptoms, signs/symptoms of adrenal insufficiency; cushingoid appearance.
Drug Interactions
Increased serum levels w/ CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, erythromycin). Decreased serum levels w/ CYP3A4 inducers (e.g. dexamethasone, rifampicin, phenytoin).
Potentially Fatal: Increased risk of adverse effects w/ simvastatin, lovastatin and CYP3A4 substrates w/ narrow therapeutic range (e.g. ciclosporin, pimozide, ergotamine). Antagonises the effect of glucocorticoids. Increased risk of vag bleeding w/ anticoagulants.
Food Interaction
Increased serum levels w/ grapefruit juice. Reduced serum levels w/ St John’s wort.
Action
Description: Mifepristone is a synthetic steroid which blocks the effects of progesterone by competitively binding to the intracellular progesterone receptor. It sensitises the myometrium to the contraction-inducing action of prostaglandin. At higher doses, it blocks the effect of cortisol at the glucocorticoid receptor while increasing circulating cortisol concentrations.
Pharmacokinetics:
Absorption: Rapidly absorbed. Bioavailability: Approx 70%. Time to peak plasma concentration: Approx 1-2 hr.
Distribution: Enters breast milk. Plasma protein binding: Approx 98%, mainly to α1-acid glycoprotein.
Metabolism: Undergoes hepatic oxidative metabolism by CYP3A4 isoenzyme.
Excretion: Via faeces (as metabolites) and urine (small amounts). Elimination half-life: Approx 18 hr.
Chemical Structure

Chemical Structure Image
Mifepristone

Source: National Center for Biotechnology Information. PubChem Database. Mifepristone, CID=55245, https://pubchem.ncbi.nlm.nih.gov/compound/Mifepristone (accessed on Jan. 22, 2020)

Storage
Store at 25°C.
ATC Classification
G03XB01 - mifepristone ; Belongs to the class of antiprogestogens.
References
Anon. Mifepristone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/01/2016.

Buckingham R (ed). Mifepristone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/01/2016.

Korlym Tablet (Corcept Therapeutics Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/01/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Mifepristone. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 20/01/2016.

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