Drugs List

Therapeutic Indications

Uses

Medical termination of pregnancy up to 63 days gestation

Administration

The mifepristone tablet is taken in a single oral dose.

Misoprostol vaginal tablets can be administered by a health care provider (place two tablets on each side of the cervix in vaginal vault) or by the woman herself.

The woman should be instructed to clean her hands thoroughly, before inserting the misoprostol vaginal tablets as high as possible into the vagina, and remain recumbent for at least 30 minutes.

Contraindications

Children under 18 years
Suspected ectopic pregnancy
Breastfeeding
Chronic adrenal failure
Ectopic pregnancy
Porphyria
Severe uncontrolled asthma

Precautions and Warnings

Risk factors for cardiovascular disorder
Hepatic impairment
Infective endocarditis
Malnutrition
Prosthetic heart valve
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Anti-D immunoglobulin recommended for non immunised rhesus negative women
Failed/incomplete abortion - therapy for complete evacuation must be given
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
Treat and control infections prior to commencing therapy
Perform a complete physical and gynaecological examination before therapy
Investigate persistent or recurrent vaginal bleeding
Termination of pregnancy must be confirmed at follow-up visit
Advise patient of potential side effects and risks associated with therapy
Advise patient to inform doctor if vomiting occurs after administration
Advise patient to report any abdominal or pelvic pain
Vomiting or severe diarrhoea may impair efficacy
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

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 without fever or other symptoms of infection. These reports occurred when medical abortion was initiated with 200mg mifepristone followed by the non-authorised vaginal administration of misoprostol tablets for oral use.

Pregnancy and Lactation

Pregnancy

This formulation of misoprostol is indicated only for termination of 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.

Use in pregnancy has been associated with birth defects/malformations for ongoing pregnancies exposed to misoprostol and mifepristone or misoprostol alone. Prenatal exposure to misoprostol has been associated with Moebius syndrome and with amniotic band syndrome. Women considering medical termination of pregnancy should be precisely counselled on the risks to their foetus if an abortion failure occurs and a second termination of pregnancy procedure is not desirable.

There is currently no relevant clinical data that suggest the possible occurrence of malformation after vaginal use of misoprostol during pregnancy. However, in a few cases where misoprostol was self-administered (orally or vaginally) in order to induce abortion, the following deleterious effects of misoprostol have been suggested: malformations of limbs, of foetus movements and of cranial nerves (hypomimia, abnormalities in suckling, deglutition, and eye movements). To date, a risk of malformations cannot be excluded.

Lactation

Mifepristone with misoprostol is contraindicated during breast-feeding.

The manufacturer indicates that the use of mifepristone and misoprostol should be avoided during breastfeeding. Mifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, clinical data is limited.

Low levels of misoprostol may be excreted in breast milk, adverse effects in breastfed infants are not expected.

Side Effects

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

Presentation

1 oral tablet containing mifepristone and 4 vaginal tablets containing misoprostol.

Drugs List

Therapeutic Indications

Uses

Medical termination of pregnancy up to 63 days gestation

Dosage

Adults

Administration

The mifepristone tablet is taken in a single oral dose.

Misoprostol vaginal tablets can be administered by a health care provider (place two tablets on each side of the cervix in vaginal vault) or by the woman herself.

The woman should be instructed to clean her hands thoroughly, before inserting the misoprostol vaginal tablets as high as possible into the vagina, and remain recumbent for at least 30 minutes.

Contraindications

Children under 18 years
Suspected ectopic pregnancy
Breastfeeding
Chronic adrenal failure
Ectopic pregnancy
Porphyria
Severe uncontrolled asthma

Precautions and Warnings

Risk factors for cardiovascular disorder
Hepatic impairment
Infective endocarditis
Malnutrition
Prosthetic heart valve
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Anti-D immunoglobulin recommended for non immunised rhesus negative women
Failed/incomplete abortion - therapy for complete evacuation must be given
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
Treat and control infections prior to commencing therapy
Perform a complete physical and gynaecological examination before therapy
Investigate persistent or recurrent vaginal bleeding
Termination of pregnancy must be confirmed at follow-up visit
Advise patient of potential side effects and risks associated with therapy
Advise patient to inform doctor if vomiting occurs after administration
Advise patient to report any abdominal or pelvic pain
Vomiting or severe diarrhoea may impair efficacy
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

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 without fever or other symptoms of infection. These reports occurred when medical abortion was initiated with 200mg mifepristone followed by the non-authorised vaginal administration of misoprostol tablets for oral use.

Pregnancy and Lactation

Pregnancy

This formulation of misoprostol is indicated only for termination of 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.

Use in pregnancy has been associated with birth defects/malformations for ongoing pregnancies exposed to misoprostol and mifepristone or misoprostol alone. Prenatal exposure to misoprostol has been associated with Moebius syndrome and with amniotic band syndrome. Women considering medical termination of pregnancy should be precisely counselled on the risks to their foetus if an abortion failure occurs and a second termination of pregnancy procedure is not desirable.

There is currently no relevant clinical data that suggest the possible occurrence of malformation after vaginal use of misoprostol during pregnancy. However, in a few cases where misoprostol was self-administered (orally or vaginally) in order to induce abortion, the following deleterious effects of misoprostol have been suggested: malformations of limbs, of foetus movements and of cranial nerves (hypomimia, abnormalities in suckling, deglutition, and eye movements). To date, a risk of malformations cannot be excluded.

Lactation

Mifepristone with misoprostol is contraindicated during breast-feeding.

The manufacturer indicates that the use of mifepristone and misoprostol should be avoided during breastfeeding. Mifepristone is a lipophilic compound and may theoretically be excreted in the mother's breast milk. However, clinical data is limited.

Low levels of misoprostol may be excreted in breast milk, adverse effects in breastfed infants are not expected.

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.

Inform patients of risks and requirements of procedure.

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

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 (This is bleeding that lasts longer than 12 days and/or that is heavier than normal menstrual bleeding).

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

Side Effects

Chills
Cramp
Diarrhoea
Dizziness
Endometritis
Epidermal necrolysis
Erythema nodosum
Erythroderma
Fever
Headache
Hot flushes
Hypersensitivity reactions
Hypotension
Infections
Malaise
Nausea
Pelvic inflammatory disease
Rash
Septic shock
Urticaria
Uterine contractions
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: January 2020

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Medabon Combipack of Mifepristone 200 mg tablet and 4 x 0.2 mg vaginal tablets. Sun pharmaceutical industries Europe B.V. Revised June 2018.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 January 2020

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
'Mifepristone' Last revised: 03 December 2018
'Misoprostol' Last revised: 31 October 2018
Last accessed: 22 January 2020