Effective 1 February 2015 a composite pack (MS-2 Step) containing mifepristone and misoprostol is PBS listed for medical termination of an intrauterine pregnancy up to 63 days' gestation.
The new listing replaces the previous listing, in which the two agents were supplied separately, and the amended restriction allowing use up to 63 days replaces the previous restriction for use up to 49 days' gestation.
The Pharmaceutical Benefits Advisory Committee recommended the listing of the composite pack for medical termination of up to 63 days' gestation on the basis of similar effectiveness compared with surgical termination.
The PBAC concluded that medical termination of pregnancy had similar clinical efficacy to that of surgical termination, and comparable safety when used up to 63 days compared with use up to 49 days of gestation.1
Registration required for prescribers or dispensers
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).
New presentation and important changes to administration
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
Proven efficacy up to 63 days' gestation when misoprostol administered buccally
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
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
Comparable safety to that of termination up to 49 days' gestation
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.
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
What to consider before prescribing
- 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 more information
- Pharmaceutical Benefits Advisory Committee. July 2014 PBAC Meeting – Positive Recommendations. Australian Government Department of Health, 2014. [Online] (accessed 1 September 2014).
- MS Health. Product information MS-2 Step. 2014. [Online] (accessed 1 September 2014).
- Ngoc NT, Blum J, Raghavan S, et al. Comparing two early medical abortion regimens: mifepristone+misoprostol vs. misoprostol alone. Contraception 2011;83:410–7. [PubMed]
- Winikoff B, Dzuba IG, Creinin MD, et al. Dzuba IG. Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial. Obstet Gynecol 2008;112:1303–10. [Online]
- Chong E, Tsereteli T, Nguyen NN, et al. A randomized controlled trial of different buccal misoprostol doses in mifepristone medical abortion. Contraception 2012;86:251–6. [PubMed]
- Sitruk-Ware R Mifepristone and misoprostol sequential regimen side effects, complications and safety. Contraception 2006;74:48–55. [PubMed]
- Cabezas E. Medical versus surgical abortion. Int J Gynaecol Obstet 1998;63[suppl.1]:S141–6. [PubMed]
- Creinin MD. Randomized comparison of efficacy, acceptability and cost of medical versus surgical abortion. Contraception 2000;62:117–24. [PubMed]
- Elul B, Ellertson C, Winikoff B, et al. Side effects of mifepristone-misoprostol abortion versus surgical abortion. Data from a trial in China, Cuba, and India. Contraception 1999;59:107–14. [PubMed]
- Winikoff B, Sivin I, Coyaji KJ, et al. Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: a comparative trial of mifepristone-misoprostol versus surgical abortion. Am J Obstet Gynecol 1997;176:431–7. [PubMed]