Mifepristone


Full Generic Medicine Info
Dosage/Direction for Use

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 hours later. Alternatively, 200 mg as a single dose, followed by gemeprost 1 mg vaginally 36-48 hours later.

Oral
Termination of pregnancy up to 63 days
Adult: 600 mg as a single dose, followed by gemeprost 1 mg vaginally 36-48 hours later. Alternatively, 200 mg as single dose, followed 36-48 hours later, by gemeprost 1 mg vaginally.

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

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

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

Oral
Hyperglycaemia in patients with Cushing's syndrome
Adult: Initially, 300 mg once daily, may increase in increments of 300 mg at intervals of 2-4 weeks according to tolerability and symptom control. Max: 1,200 mg once daily, not to exceed 20 mg/kg/day.
Renal impairment: Max: 600 mg once daily.
Hepatic impairment: Mild to moderate: Max: 600 mg.

Special Populations: Hyperglycaemia in patients with Cushing's syndrome: Patient taking strong CYP3A4 inhibitors: Max: 900 mg once daily.
Administration
May be taken with or without food. Avoid grapefruit juice.
Contraindications
Termination of pregnancy: Chronic adrenal failure, uncontrolled severe asthma, inherited porphyria, intrauterine device in place, ectopic pregnancy, pregnancy not confirmed by ultrasound scan or biological test, suspected extra-uterine pregnancy, undiagnosed adnexal mass, haemorrhagic disorder. Concomitant use with anticoagulant or long-term corticosteroid therapy. Treatment of hyperglycaemia in patients with Cushing's syndrome: History of unexplained vaginal bleeding, endometrial hyperplasia with atypia or endometrial carcinoma. Pregnancy. Concomitant use with lovastatin, simvastatin or CYP3A substrates with narrow therapeutic ranges (e.g. ciclosporin, fentanyl, quinidine, tacrolimus, sirolimus, dihydroergotamine, ergotamine), long-term corticosteroid therapy for life-saving purposes (e.g. immunosuppression following organ transplant).
Special Precautions
Termination of pregnancy: Patient with history and active CV disease, haemostatic disorders, hypocoagulability, anaemia. Treatment of hyperglycaemia in patients with Cushing's syndrome: Patient with haemorrhagic disorder, hypokalaemia, adrenal insufficiency, CV disease. Concomitant use with anticoagulants, QT-prolonging agents, strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin). Hepatic and renal impairment. Lactation. Patient counselling This drug may cause dizziness, if affected, do not drive or operate machinery. Monitoring Parameters Termination of pregnancy: Monitor Hb, haematocrit and RBC count in cases of heavy bleeding; CBC in patients who show signs of infection. Confirm pregnancy and Rh status prior to termination of pregnancy. Conduct clinical exam, hCG testing or ultrasound to confirm complete termination of pregnancy. Treatment of hyperglycaemia in patients with Cushing's syndrome: Monitor K level (1-2 weeks after initiation or dose increase, then periodically thereafter), thyroid function, blood sugar, psychiatric symptoms and cushingoid appearance. Monitor for signs and symptoms of adrenal insufficiency.
Adverse Reactions
Significant: Adrenal insufficiency, hypokalaemia, QT prolongation. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal cramps, dry mouth, constipation. General disorders and administration site conditions: Fatigue, peripheral oedema. Infections and infestations: Bacterial or viral infection, sinusitis, nasopharyngitis. Investigations: Abnormal thyroid function test. Metabolism and nutrition disorders: Decreased appetite, anorexia. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain, pain in extremity. Nervous system disorders: Headache, dizziness, somnolence. Psychiatric disorders: Anxiety. Reproductive system and breast disorders: Uterine contractions, endometrial hypertrophy. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Rash, toxic epidermal necrolysis. Vascular disorders: Hypertension.
Potentially Fatal: Toxic and septic shock.
Drug Interactions
Increased serum concentration with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin). Decreased serum concentration with CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine). May increase serum concentration of CYP2C8/2C9 substrates (e.g. fluvastatin, NSAIDs, repaglinide) and CYP2B6 substrates (e.g. efavirenz, bupropion). May diminish the therapeutic effect of hormonal contraceptives. May enhance the effect of QT-prolonging agents.
Potentially Fatal: May increase serum concentration of simvastatin, lovastatin, CYP3A substrates with narrow therapeutic ranges (e.g. ciclosporin, fentanyl, quinidine, tacrolimus, sirolimus, dihydroergotamine, ergotamine). May diminish the therapeutic effect of corticosteroids (e.g. dexamethasone). May enhance the adverse effect of anticoagulants (e.g. warfarin).
Food Interaction
Decreased serum concentration with St. John's wort. Increased serum concentration with grapefruit juice.
Action
Mifepristone is a synthetic steroid derived from norethisterone. At low doses, it blocks the effects of progesterone by competitively binding with progesterone at the progesterone receptor. In the absence of progesterone, it functions as a partial progesterone agonist. During pregnancy, mifepristone sensitises the myometrium to the contraction-inducing effect of prostaglandins. At high doses, it suppresses cortisol's function at the glucocorticoid receptor while increasing cortisol level when used as a treatment of hyperglycaemia in patients with Cushing's syndrome.
Absorption: Rapidly absorbed. Bioavailability: 69%. Time to peak plasma concentration: 1-2 hours (single dose); 1-4 hours (multiple doses).
Distribution: Distributed to tissues, including the CNS. Enters breast milk (small amount). Plasma protein binding: 98%, mainly to α1-acid glycoprotein and albumin.
Metabolism: Metabolised in the liver by CYP3A4 via N-demethylation and terminal hydroxylation into 3 metabolites.
Excretion: Mainly via faeces (approx 90%); urine (approx 10%). Terminal elimination half-life: 18 hours (single dose, following a slower phase where 50% eliminated between 12-72 hours); 85 hours (multiple doses).
Storage
Oral: Store at 25°C.
CIMS Class
Drugs Acting on the Uterus
ATC Classification
G03XB01 - mifepristone ; Belongs to the class of antiprogestogens.
Disclaimer: This information is independently developed by CIMS based on mifepristone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 CIMS. All rights reserved. Powered by CIMSAsia.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in