Drugs List

Therapeutic Indications

Uses

Labour induction in foetal death in utero
Medical termination of pregnancy up to 63 days gestation
Softening/dilatation of cervix before termination of pregnancy
Termination of pregnancy between 13-24 weeks gestation (with prostaglandin)

Medical termination of developing intra-uterine pregnancy of up to 63 days gestation, in sequential use with a prostaglandin analogue.

Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy in women with no more than 83 days of amenorrhoea.

Preparation for the action of prostaglandin analogues in the termination of pregnancy beyond the first trimester (for medical reasons).

Labour induction in foetal death in utero, in patients where prostaglandin or oxytocin cannot be used.

For termination of pregnancy mifepristone may only be administered in accordance with the Abortion Act 1967 as amended by The Human Fertilisation and Embryology Act 1990.
As a consequence, when used for termination of pregnancy, mifepristone and any treatment necessary to effect complete termination of the pregnancy can only be prescribed by a medical doctor and administered in an NHS or non-NHS hospital or centre (having approval to undertake termination of pregnancy). The product will be administered under the supervision of a medical practitioner.

Regional differences may exist in the laws governing the use of this product (e.g. Northern Ireland).

Contraindications

Suspected ectopic pregnancy
Breastfeeding
Chronic adrenal failure
Chronic renal failure
Ectopic pregnancy
Malnutrition
Porphyria
Severe hepatic impairment
Severe uncontrolled asthma

Precautions and Warnings

Risk factors for cardiovascular disorder
Anaemia
Asthma
Cardiovascular disorder
Coagulopathy

Anti-D immunoglobulin recommended for non immunised rhesus negative women
Failed/incomplete abortion - therapy for complete evacuation must be given
Not all available strengths are licensed for all indications
Only for use at approved centres under medical supervision
Regional differences may exist in the law governing use of this product
Remove intra-uterine device (IUD) before starting treatment
If acute adrenal failure is suspected, administer dexamethasone
Investigate persistent or recurrent vaginal bleeding
Monitor patient for 3 hours after treatment
Termination of pregnancy must be confirmed at follow-up visit
Advise patient of potential side effects and risks associated with therapy
Female: Avoid conception during the next menstrual cycle
Conception may occur before resumption of menses
Patient must receive written info (including for heavy bleeding/emergency)
Patients should be counselled regarding pregnancy after treatment complete

In cases of suspected acute adrenal failure, dexamethasone administration is recommended. Dexamethasone 1 mg antagonises a dose of 400 mg mifepristone.

Due to the antiglucocorticoid activity of mifepristone, the efficacy of long-term corticosteroid therapy including inhaled corticosteroids in asthmatic patients may be decreased during the three to four days following intake of mifepristone. Therapy should be adjusted accordingly.

Clinicians should be aware of very rare reports of fatal toxic shock syndrome without fever or other symptoms of infection. These reports occurred when medical abortion was initiated with 200 mg mifepristone followed by the non-authorised vaginal administration of misoprostol tablets for oral use.

Pregnancy and Lactation

Pregnancy

In animals, the abortifacient effect of mifepristone precludes the proper assessment of any teratogenic effect of the molecule.

With subabortive 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, women 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.

Lactation

Mifepristone use should be avoided during breast-feeding.

Mifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, no clinical data is available.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Angioedema
Chills
Diarrhoea
Dizziness
Endometritis
Epidermal necrolysis
Erythema nodosum
Erythroderma
Fever
Headache
Hot flushes
Hypersensitivity reactions
Hypotension
Intestinal cramp
Malaise
Nausea
Pelvic inflammatory disease
Rash
Septic shock
Urticaria
Uterine contractions
Uterine cramps
Uterine rupture
Vaginal bleeding
Vomiting

Presentation

Tablets containing mifepristone

Drugs List

Therapeutic Indications

Uses

Labour induction in foetal death in utero
Medical termination of pregnancy up to 63 days gestation
Softening/dilatation of cervix before termination of pregnancy
Termination of pregnancy between 13-24 weeks gestation (with prostaglandin)

Medical termination of developing intra-uterine pregnancy of up to 63 days gestation, in sequential use with a prostaglandin analogue.

Softening and dilatation of the cervix uteri prior to surgical termination of pregnancy in women with no more than 83 days of amenorrhoea.

Preparation for the action of prostaglandin analogues in the termination of pregnancy beyond the first trimester (for medical reasons).

Labour induction in foetal death in utero, in patients where prostaglandin or oxytocin cannot be used.

For termination of pregnancy mifepristone may only be administered in accordance with the Abortion Act 1967 as amended by The Human Fertilisation and Embryology Act 1990.
As a consequence, when used for termination of pregnancy, mifepristone and any treatment necessary to effect complete termination of the pregnancy can only be prescribed by a medical doctor and administered in an NHS or non-NHS hospital or centre (having approval to undertake termination of pregnancy). The product will be administered under the supervision of a medical practitioner.

Regional differences may exist in the laws governing the use of this product (e.g. Northern Ireland).

Dosage

Adults

Contraindications

Suspected ectopic pregnancy
Breastfeeding
Chronic adrenal failure
Chronic renal failure
Ectopic pregnancy
Malnutrition
Porphyria
Severe hepatic impairment
Severe uncontrolled asthma

Precautions and Warnings

Risk factors for cardiovascular disorder
Anaemia
Asthma
Cardiovascular disorder
Coagulopathy

Anti-D immunoglobulin recommended for non immunised rhesus negative women
Failed/incomplete abortion - therapy for complete evacuation must be given
Not all available strengths are licensed for all indications
Only for use at approved centres under medical supervision
Regional differences may exist in the law governing use of this product
Remove intra-uterine device (IUD) before starting treatment
If acute adrenal failure is suspected, administer dexamethasone
Investigate persistent or recurrent vaginal bleeding
Monitor patient for 3 hours after treatment
Termination of pregnancy must be confirmed at follow-up visit
Advise patient of potential side effects and risks associated with therapy
Female: Avoid conception during the next menstrual cycle
Conception may occur before resumption of menses
Patient must receive written info (including for heavy bleeding/emergency)
Patients should be counselled regarding pregnancy after treatment complete

In cases of suspected acute adrenal failure, dexamethasone administration is recommended. Dexamethasone 1 mg antagonises a dose of 400 mg mifepristone.

Due to the antiglucocorticoid activity of mifepristone, the efficacy of long-term corticosteroid therapy including inhaled corticosteroids in asthmatic patients may be decreased during the three to four days following intake of mifepristone. Therapy should be adjusted accordingly.

Clinicians should be aware of very rare reports of fatal toxic shock syndrome without fever or other symptoms of infection. These reports occurred when medical abortion was initiated with 200 mg mifepristone followed by the non-authorised vaginal administration of misoprostol tablets for oral use.

Pregnancy and Lactation

Pregnancy

In animals, the abortifacient effect of mifepristone precludes the proper assessment of any teratogenic effect of the molecule.

With subabortive 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, women 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.

Lactation

Mifepristone use should be avoided during breast-feeding.

Mifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, no clinical data is available.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

The treatment procedure should be fully explained and completely understood by the patient. A patient information leaflet should be made available appropriate to the indication.

The patient should be made aware of the importance of follow up visits and should be given precise instructions on whom she should contact and where to go in the event of any problems, particularly in the case of very heavy vaginal bleeding.

The patient should be advised to inform the doctor if she vomits shortly after administration of the mifepristone.

The patient should be advised not to travel far away from the treatment centre until complete expulsion has been reported.

Side Effects

Angioedema
Chills
Diarrhoea
Dizziness
Endometritis
Epidermal necrolysis
Erythema nodosum
Erythroderma
Fever
Headache
Hot flushes
Hypersensitivity reactions
Hypotension
Intestinal cramp
Malaise
Nausea
Pelvic inflammatory disease
Rash
Septic shock
Urticaria
Uterine contractions
Uterine cramps
Uterine rupture
Vaginal bleeding
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Mifegyne. Exelgyn Laboratories. Revised March 2015.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 28 September 2017