Mifepristone and misoprostol (MS-2 Step) composite pack: use extended to 63 days’ gestation

There are no changes to the arrangements for prescribers or dispensers of the composite pack and the requirement remains for prescribers and dispensers to be certified by MS Health (www.ms2step.com.au).

Composite pack indicated for termination up to 63 days' gestation

The change to the PBS listing is consistent with the revised Therapeutic Goods Administration indication for a composite pack (MS-2 Step) containing mifepristone (Mifepristone Linepharma) 200 mg (one tablet) and misoprostol (GyMiso) 200 micrograms (four tablets per pack) for women of childbearing age for the medical termination of an intrauterine pregnancy of up to 63 days' gestation.²

New requirement for buccally administered misoprostol

No change is required for administration of mifepristone, which continues to be one 200 mg tablet orally, followed 36–48 hours later by the administration of the misoprostol.

With the new composite pack, the method of administration for misoprostol is 800 micrograms of misoprostol (four tablets, each containing 200 micrograms) taken buccally. Advise women to keep each tablet between the cheek and gum for 30 minutes before swallowing any remaining fragments with water.²

Whereas previously it was acceptable for misoprostol to be taken orally or buccally, the new indication for medical termination up to 63 days requires misoprostol be administered buccally to maintain efficacy for gestational ages beyond 49 days.²

High success rate for complete termination of pregnancy

In clinical trials mifepristone (200 mg) followed 24–48 hours later by misoprostol (800 micrograms) administered buccally offered a safe and effective means for medical termination of pregnancy up to 63 days' gestation.^2-5

Overall a success rate of about 96% for complete termination of pregnancy was achieved,^2-5 with a low (1–2%) rate of ongoing pregnancy.^2-4

Efficacy beyond 49 days' gestation requires buccal delivery

For termination of pregnancies up to 49 days' gestation, similar success rates were observed whether misoprostol was administered by the oral or buccal routes.

Beyond 49 days, success with buccal administration was maintained at about 95% whereas success with oral administration fell below 90%.⁴

The safety profile for mifepristone followed by misoprostol for medical termination up to 63 days' gestation is consistent with that seen for gestational age up to 49 days.

Heavy uterine bleeding and painful uterine contractions or cramps may be expected,⁶ and are more likely to be experienced by women choosing medical over surgical termination.^7-10

These and most other side effects such as diarrhoea, nausea, vomiting, dizziness, fever, chills and headache are associated with the misoprostol component.²

In one study, fever and chills were reportedly about 10% more common when misoprostol was administered buccally compared with oral administration.⁴

Bleeding occurs in most cases

In most women bleeding and expulsion occurs within 3–4 hours of misoprostol administration and vaginal bleeding continues for 10–16 days.

Heavy bleeding can be expected for 2–3 days after misoprostol administration but is rarely associated with anaemia or the need for blood transfusion, although these can occur.

Advise women to seek medical advice if very heavy bleeding is experienced for any longer than expected.²

Follow-up is essential

Persistent bleeding can be a consequence of incomplete expulsion or an unnoticed extrauterine pregnancy and may require surgical intervention. Follow-up within 14–21 days after administration of mifepristone to verify complete expulsion and that vaginal bleeding has stopped.

When persistent bleeding is reported at the follow-up appointment, even if light, check within a few days for cessation of bleeding.²

Until follow-up has taken place, advise patients to remain close to a facility where treatment can be accessed in case of severe or prolonged bleeding.

If mifepristone and misoprostol fails to cause termination of an intrauterine pregnancy, and ongoing pregnancy is confirmed on ultrasound, discuss treatment options, which may include offering termination of pregnancy by a surgical method.²

• Confirm pregnancy and gestational age (not more than 63 days) via ultrasound, remove any intrauterine device and ensure ectopic pregnancy is excluded.²
• Exclude contraindications to mifepristone and misoprostol, eg:²
  • chronic adrenal failure
  • severe disease requiring steroid administration
  • hypocoagulation diseases
  • anticoagulation therapy
  • allergy to mifepristone, misoprostol or other prostaglandin.
• Consider any conditions in which medical termination is not recommended (eg, anaemia, renal failure, hepatic impairment, malnutrition or cardiovascular disease).²

For details on using mifepristone and misoprostol, refer to the August 2013 full NPS RADAR review on mifepristone and misoprostol for medical termination of pregnancy up to 49 days' gestation.