Instructions on preparing the oral preparation of misoprostol for doses less than 200 micrograms are given at the end of this guideline.

First trimester (less than 12 weeks)

See paper based gynaecological guidance.

From 12 to 23+6 weeks

200 mg of mifepristone PO is given on day 1 and the patient admitted to hospital 36-48 hours later for 400 micrograms misoprostol PV. The 400 microgram misoprostol PV is repeated 3 hourly to a maximum of 5 doses in total.

The vaginal route is associated with reduced side effects but equal efficacy - women should be advised of this.

Consider the oral route if there is heavy vaginal bleeding, heavy vaginal discharge or have failed induction.

From 24 to 26+6 weeks

200 mg of mifepristone PO is given on day 1 and the patient admitted to hospital 36-48 hours later for 100 micrograms misoprostol PO. The 100 micrograms misoprostol PO is repeated 6 hourly up to 24 hours.

From 27 weeks

200 mg of mifepristone PO is given on day 1 and the patient admitted to hospital 36-48 hours later for 25-50 micrograms PO four hourly. This is repeated up to 24 hours.

Previous caesarean section

Use of the above regime is considered safe if there is one previous caesarean section. Please discuss with a consultant if there is more than one uterine scar or an atypical scar.

If labour does not establish

If labour does not establish with above regimens then consultant involvement is appropriate. Options include repeating the dosage schedule (including the mifepristone), increasing the misoprostol, or changing to prostin.

• blood to be taken for group and save - see also stillbirth bloods if appropriate
• pessaries may be inserted by a midwife, nurse or doctor at the discretion of the midwife involved
• analgesia may be given as required
• normal diet should be offered throughout

• after delivery of the fetus:
  • give 10 IU IM syntocinon 
  • it is important to ensure that the placenta is complete and that the uterus is well contracted
  • if the placenta is retained, wait at least 1 hour unless bleeding is heavy
  • if the placenta is not expelled within 1 hour of delivery of the fetus or there are concerns regarding bleeding notify the on-call registrar

• if the TOP is because of fetal abnormality
  • offer to send the fetus and placenta for post mortem
  • if for fetal abnormality, the PM form should be sent copies of correspondence and with a lithium heparin tube and an EDTA tube from each parent to run against the baby’s genetic results
  • forms are from Clinical Genetics at Western General (Google 'WGH genetics forms')
  • follow up to discuss fetal abnormality results should be made directly with the relevant consultant, and not by adding the patient to a clinic

• if the TOP is for any other reason:
  • place the fetus and placenta into white specimen pot (dry, not formalin)
  • seal tightly and place in the clear polythene bag
  • complete ‘Certificate in Respect of Fetal Remains’ form, attach to outside of polythene bag and transfer to laboratory fridge
  • record details in TOP book (labour ward filing cabinet)

• give Anti D 500 IU IM if rhesus negative

Expected Side Effects

Mifepristone:

• malaise
• faintness
• headache
• nausea and vomiting
• vaginal bleeding
• uterine cramps
• skin rashes, rarely

Misoprostol:

• diarrhoea and rash (1 in 10)
• abdominal pain
• dizziness
• headache
• dyspepsia
• flatulence
• nausea and vomiting
• hypotension, rarely, with doses greater than 800 micrograms

NB symptoms of misoprostol are reported as being dose related

Contra-indications

Mifepristone:

• known allergy to mifepristone
• chronic adrenal failure
• long-term corticosteroid therapy
• haemorrhagic disorders
• treatment with anticoagulants

Misoprostol:

• known allergy to prostaglandins
• inflammatory bowel disease

Caution in

• asthmatics and patients with COAD (mifepristone)
• patients with cardiovascular disease (mifepristone and misoprostol)

Preparation of misoprostol 200microgram in 200ml Water

For use in conjunction with Late Intrauterine Fetal Death and Stillbirth – Royal College of Obstetricians and Gynaecologists Green-top Guideline No. 55

Equipment:

• 200 ml glass medicine bottle
• tablet crusher (dedicated for use with misoprostol)
• 1 x misoprostol 200 microgram tablet
• water
• gloves and mask  - to be worn while preparing solutions

Method:

1. Crush misoprostol 200 microgram tablet in tablet crusher.
2. Add to 200 ml glass medicine bottle.
3. Add a proportion of water and shake bottle to dissolve misoprostol powder.
4. Add water up to 200 ml volume.

Label

Misoprostol - the following info to be completed:

• 200micrograms in 200ml (1 microgram 1ml)
• 100 micrograms in 100 ml
• 50 micrograms in 50 ml
• 25 micrograms in 25 ml
• Dose (amount per administration)
• Patients Name
• Date & Time Prepared
• Prepared By                               
• Checked By
• Do Not Use After (24 hours after preparation)
• Shake Well Before Use.
• Keep Out of Reach of Children
• Batch Number of Tablet

Other Information:

• each prepared solution is for single patient use - the patient's addressograph should be attached to the bottle in addition to name on the label
• doses should be prescribed on patient’s drug chart, administered and recorded in the normal manner
• any solution remaining after treatment is completed should be disposed of

Royal College of Obstetricians and Gynaecologists. Late intrauterine fetal death and stillbirth (green-top guideline No.55) Nov 2010

NICE. Induction of labour in late intrauterine fetal death: vaginal misoprostol (after oral mifepristone). Evidence summary (ESUOM 11) Apr 2013 www.nice.org.uk/advice/esuom11