Mifepristone

Registered South African indications:

• Termination of intra-uterine pregnancy
• Labour induction after foetal death in utero

Contraindications

Registered South African contraindications

• Known hypersensitivity to mifepristone or to any of the excipients
• Chronic adrenal failure
• Asthmatics (severe asthma uncontrolled by corticosteroid therapy) and other patients with chronic obstructive airways disease
• Inherited porphyria
• Suspected ectopic pregnancy
• Pregnancy not confirmed by an ultrasound or biological test
• Pregnancy beyond 63 days of amenorrhoea
• Pregnancy of 84 days of amenorrhoea and beyond (For the indication of softening and dilation of the cervix prior to surgical termination of pregnancy)
• Contraindication to the prostaglandin analogue selected
• Long-term corticosteroid therapy
• Haemorrhagic disorders and treatment with anticoagulants
• Unremoved intra-uterine contraceptive device

Contraindications registered in other jurisdictions

• Known hypersensitivity to the active substance or to any of the excipients
• Chronic adrenal failure
• Asthma uncontrolled by therapy
• Inherited porphyria
• Pregnancy not confirmed by an ultrasound or biological test
• Pregnancy beyond 63 days of amenorrhea
• Suspected ectopic pregnancy
• Contraindication to the prostaglandin analogue selected

Cautions

• Breastfeeding
• Renal impairment 
• Hepatic impairment
• Malnutrition
• Haemostatic disorders
• Asthma
• Cardiovascular disease

Forms avail. in SA and covered in this monograph: tab

South African registered indications and dosages

Termination of intra-uterine pregnancy
- Medical termination of intra-uterine pregnancy up to 63 days after the last menstrual period (Additional agent may be required)

• Oral (tab): Initial: 200mg, as a single dose; A suitable prostaglandin analogue should be administered 36-48hrs later unless abortion has already been completed

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If significant discomfort, excessive bleeding or other adverse reactions occur, the patient should be given instructions and a contact number for emergencies

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- Softening and dilation of the cervix uteri prior to surgical pregnancy termination during the first trimester

• Oral (tab): 200mg, to be taken 36-48hrs before (but not beyond) the surgical termination of pregnancy

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Softening and dilation has been shown to be detectable from 24 hours after administration and increases to a maximum approximately 36-48 hours after administration

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Surgery should be performed no later than 48 hours after administration as the risk of bleeding and abortion increases if the elapsed time is more than 48 hours, particularly with pregnancies of earlier gestations (less than 9 weeks)

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- For use in combination with a prostaglandin analogue for termination of pregnancy between 13 and 20 weeks gestation

• Oral (tab): 600mg (3 x 200mg tab), as a single dose followed 36-48hrs later by a prostaglandin analogue

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The prostaglandin analogue is to be repeated as many times as necessary. If abortion does not occur within 48 hours after the first prostaglandin analogue administration, an alternative procedure of uterine emptying should be followed. It is not necessary to perform a dilation and curettage procedure if a complete abortion has occurred

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Labour induction after foetal death in utero
- In patients where prostaglandin or oxytocin cannot be used

• Oral (tab): 600mg (3 x 200mg tab), taken as a single dose for 2 consecutive days

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Labour should be induced by the usual methods if it has not started within 72 hours following the first administration. The dosage is independent of body weight

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All indications: Mifepristone must not be administered if there is doubt as to the existence or age of the pregnancy. In this case perform an ultrasound scan and/or measure the HCG before administration

No information available

Pregnancy

South African recommendations

• Pregnancy not confirmed by an ultrasound or biological test: Contraindicated
• Pregnancy beyond 63 days of amenorrhoea: Contraindicated
• Pregnancy of 84 days of amenorrhoea and beyond (For the indication of softening and dilation of the cervix prior to surgical termination of pregnancy): Contraindicated
• Suspected ectopic pregnancy: Contraindicated
• Mifepristone is indicated for the termination of pregnancy and has no other use during pregnancy
• The patient should be informed that due to the risk of failure of the medical method of pregnancy termination and the unknown risk to the foetus, the control visit is mandatory
• Should a failure of the method be diagnosed at the control visit (viable ongoing pregnancy), and should the patient still agree, pregnancy termination should be completed by another method
• Should the patient wish to continue with her pregnancy, the available data is too limited to justify a systematic termination of an exposed pregnancy. In that event, a careful ultrasonographic monitoring of the pregnancy will be established, with a special attention to the limbs

Recommendations in other jurisdictions

• Pregnancy not confirmed by an ultrasound or biological test: Contraindicated
• Pregnancy beyond 63 days of amenorrhea: Contraindicated
• Suspected ectopic pregnancy: Contraindicated
• In animals, the abortifacient effect of mifepristone precludes the proper assessment of any teratogenic effect of the molecule
• With sub-abortive doses, isolated cases of malformations observed in rabbits, but not in rats or mice were too few to be considered significant, or attributable to mifepristone
• In humans, the few reported cases of malformations do not allow a causality assessment for mifepristone alone or associated to prostaglandin. Therefore, data is too limited to determine whether the molecule is a human teratogen
• Consequently, the patient should be informed that due to the risk of failure of the medical method of pregnancy termination and to the unknown risk to the foetus, the control visit is mandatory
• Should a failure of the method be diagnosed at the control visit (viable ongoing pregnancy), and should the patient still agree, pregnancy termination should be completed by another method
• Should the patient wish to continue with her pregnancy, the available data is too limited to justify a systematic termination of an exposed pregnancy. In that event, careful ultra-sonographic monitoring of the pregnancy should be carried out

Breastfeeding

South African recommendations

• Caution; not recommended
• It is unknown whether mifepristone is excreted in the mother's breast milk. Consequently, mifepristone use should be avoided during breastfeeding

Recommendations in other jurisdictions

• Caution; not recommended
• Mifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, limited data is available. Consequently, Mifepristone use should be avoided during breastfeeding

Fertility

South African recommendations

• Pregnancies may occur between embryo expulsion and the resumption of menses. To avoid potential exposure of a subsequent pregnancy to mifepristone, it is recommended that conception be avoided during the next menstrual cycle. Reliable contraceptive precautions should therefore commence as early as possible after mifepristone administration

Recommendations in other jurisdictions

• Mifepristone inhibited oestrus cycling in rats at doses below the clinical dose in a 3-week study. This was reversed over the following 2-3 weeks and no subsequent effects on reproductive performance were found. No human data on the effect of active substance mifepristone on fertility are available

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; no information available 

Elderly

• Not indicated for use in geriatric patients

Porphyria Information

• Contraindicated

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Malaise

Cardiovascular Disorders

• Hypotension 
• Hot flushes
• Dizziness
• Chills

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea 
• Cramping

Genitourinary Disorders

• Uterine contractions or cramping
• Heavy bleeding
• Uterine rupture

Skin and Subcutaneous Tissue Disorders

• Skin rashes 
• Urticaria
• Erythroderma
• Erythema nodosum
• Toxic epidermal necrolysis 
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Infection
• Fatal toxic and septic shock

• CYP3A4 inhibitors
• CYP3A4 inducers
• QT prolonging agents 
• Non-steroidal inflammatory drugs
• St John's Wort
• Dexamethasone

Prior to procedure

• Pregnancy test
• Rh status
• Full blood count

Post Procedure 

• Pregnancy test
• Ultrasound
• Full blood count

Mifepristone is a synthetic steroid with an antiprogestational action as a result of competition with progesterone at the progesterone receptors.

Tablet 200mg

• Mediprist 200mg (Adcock Ingram Limited)
• Mifegyne (Medi Challenge) originator