Mifepristone and misoprostol: Recommended regimen

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Last reviewed: October 1, 2022

Recommendation:

• Mifepristone 200mg orally followed 1-2 days later by misoprostol 800mcg buccally, sublingually or vaginally. The dose of misoprostol can be repeated to achieve abortion success.
• After 9 weeks gestation, routinely using at least two doses of misoprostol, administered 3-4 hours apart, improves abortion success rates.
• A combined regimen of mifepristone and misoprostol is effective and safe with abortion success rates over 95%, continuing pregnancy rates around 2% and complication rates of 1-3%.

In practice:

• A combined mifepristone and misoprostol regimen is more effective than misoprostol used alone, and is recommended for medical abortion before 13 weeks; where mifepristone is unavailable, the misoprostol-only regimen can be used.
• Additional doses of misoprostol can be used if bleeding, cramping, or pregnancy expulsion have not occurred, and at least 3 hours have passed since the previous misoprostol dose.

Strength of recommendation: Strong

Quality of evidence:

• Up to nine weeks gestation: High
• 9-13 weeks gestation: Low

Background

Medical abortion success is defined as a complete abortion that needs no further intervention. A combined regimen of mifepristone and misoprostol is recommended for medical abortion as it is more effective than misoprostol alone (Abubeker et al., 2020; Blum et al., 2012; Kapp et al., 2019; Kulier at al., 2011; Ngoc et al., 2011; Raymond, Harrison, & Weaver, 2019; World Health Organization [WHO], 2022). Where mifepristone is unavailable, the misoprostol-only regimen may be used.

Up to nine weeks (63 days since LMP)

Multiple randomized controlled clinical trials have shown that the combination of mifepristone and misoprostol
is an effective medical abortion regimen with success rates ranging from 95-98% up to nine weeks gestation (Abubeker et al, 2020; Chen & Creinin, 2015; Kapp, Baldwin, & Rodriguez, 2018; Kulier et al., 2011; Raymond et al., 2012). A 2020 systematic review of medical abortion with 200mg mifepristone and 800mcg misoprostol up to 9 weeks gestation in low- and middle-income countries included 52 studies and found an average abortion success rate of 95% (Fergeson & Scott, 2020). Vaginal, buccal and sublingual misoprostol are more effective than oral misoprostol (Kulier et al., 2011; Zhang et al., 2022). Buccal dosing (Middleton et al., 2005) and sublingual dosing (Tang et al., 2003; von Hertzen et al., 2010) have higher rates of gastrointestinal side effects than vaginal dosing (Zhang et al., 2022). Sublingual dosing is associated with more side effects than buccal dosing (Chai, Wong, & Ho, 2013). Decreasing the sublingual misoprostol dose to 400mcg decreased side effects but increased the rates of incomplete abortion and ongoing pregnancy (Bracken et al., 2014; Raghavan et al., 2013; von Hertzen et al., 2010); therefore, the recommended dose of sublingual misoprostol remains 800mcg. Buccal or sublingual dosing may be preferred over vaginal dosing to accommodate individual’s preferences or legal restrictions.

Simultaneous dosing of mifepristone and misoprostol for those with gestations up to 63 days has demonstrated a success rate of approximately 95%, compared to 97-98% when misoprostol is used 24-48 hours after mifepristone (Creinin et al., 2007; Goel et al., 2011; Lohr et al., 2018; Schmidt-Hansen et al., 2022; Verma et al., 2017). Although this method is slightly less effective, it may be preferable in certain settings, such as where home use of medical abortion drugs is restricted (Lohr et al., 2018).

Three large cohort studies, including a total of 260,256 women who had mifepristone and misoprostol medical abortions up to nine weeks gestation (Cleland et al., 2013; Gatter, Cleland, & Nucatola, 2015; Goldstone, Walker, & Hawtin, 2017), found rates of incomplete abortion treated with uterine aspiration ranging from 2.3-4.8%. A Danish cohort study which included 86,437 mifepristone and misoprostol medical abortions before nine weeks concluded that increasing gestational age was most strongly associated with requiring surgical intervention (Meaidi et al. 2019). Rates of complications observed during medical abortion with mifepristone and misoprostol up to nine weeks gestation is less than 1% (Cleland et al., 2013; Gatter, Cleland, & Nucatola, 2015; Goldstone, Walker, & Hawtin, 2017).

9-11 weeks

A 2015 review reports data from five comparative studies including 801 women with gestations between 64-70 days and 1,163 with gestations from 57-63 days (Abbas, Chong, & Raymond, 2015). In four studies, women received 200mg mifepristone followed by a single dose of 800mcg buccal misoprostol (Boersma, Meyboom-de Jong, & Kleiverda, 2011; Pena et al., 2014; Sanhueza Smith et al., 2015; Winikoff et al., 2012) and in one study, women received mifepristone and 400mcg sublingual misoprostol (Bracken et al., 2014). There was no difference in success rates between the two gestational groups (93.9% at 57-63 days compared to 92.3% at 64-70 days). and there were no differences in serious adverse events, such as hospital admissions or transfers, between the groups (0.7% and 0.5% respectively).

A prospective, open-label, non-inferiority trial compared the efficacy of a medical abortion regimen of 200mg mifepristone, followed by a single dose of 800mcg misoprostol, in 362 women at 64-70 days gestation to efficacy of the same regimen in 286 women from 71-77 days gestation (Dzuba et al., 2020b). The success rate was 92% in the 64-70 day group, with an ongoing pregnancy rate of 4%, compared to 87% and 9% in the 71-77 day group, respectively. A subsequent retrospective cohort study compared success rates when two doses of 800mcg misoprostol were taken at home, four hours apart, for pregnancies between 64-70 days and 71-77 days (Dzuba et al., 2020a). Although a high loss to follow up (25%) limits conclusions that can be drawn, investigators found abortion success rates improved to greater than 99% from 64-70 days, and 98% from 71-77 days. A 2019 systematic review of medical abortion between 63 and 84 days gestation similarly concluded that abortion success rates are higher when routine, repeated doses of misoprostol are used, and when the vaginal route is used for misoprostol administration, compared to oral (Kapp et al., 2019). However, the review does not recommend a specific mifepristone and misoprostol regimen (Kapp et al., 2019).

11-13 weeks

One trial randomized 340 women with pregnancies up to 13 weeks to two groups: 1) 200mg mifepristone followed by either 800mcg vaginal, or 2) 600mcg sublingual misoprostol administration, followed by up to two additional doses of 400mcg sublingual or vaginal misoprostol every 3 hours (Hamoda et al., 2005). The overall success rate for this regimen was 95.8%. In both groups, most people required 2 doses of misoprostol to have a successful abortion; 3.4% of those in the vaginal group required surgical evacuation of the uterus, compared to 2.9% in the sublingual group. Those using misoprostol sublingually were more likely to experience side effects. A prospective cohort study (Lokeland et al., 2010), including 254 women with pregnancies between 63 and 90 days gestation, reported an abortion success rate of 91.7% and an ongoing pregnancy rate of less than 1% using a similar regimen of mifepristone followed by repeated doses of misoprostol. Between 10 and 13 weeks, reported rates of uterine aspiration for any reason range from 4-8% (Hamoda et al., 2005; Lokeland et al., 2010) and complication rates are around 3% (Hamoda et al., 2005).

Who can provide medical abortion before 13 weeks gestation?

The World Health Organization (WHO) makes service delivery recommendations for the provision of medical abortion before 13 weeks gestation, which includes assessment of medical abortion eligibility (determining pregnancy duration and assessing for contraindications to abortion medications), administration of abortion medications, management of the abortion process, and assessment of abortion success (WHO, 2022). WHO advises that all cadres of health care workers (specialty and general medical practitioners, associate and advanced associate clinicians, midwives, nurses, auxiliary nurses and auxiliary nurse midwives, traditional and complementary medicine professionals, pharmacists and pharmacy workers, and community health workers) can safely and effectively provide medical abortion with mifepristone and misoprostol or misoprostol-only based on a variety of evidence and the expected skills and knowledge for that type of health worker (WHO, 2022). WHO also recommends that the pregnant person can safely and effectively self-manage the medical abortion process, in whole or in part, when they have access to accurate information, quality assured medications including for pain management, the support of trained health care workers, and access to a health facility if needed (WHO, 2022). For more information about self-managed medical abortion, see 3.5.2: Recommendations for abortion before 13 weeks: Medical abortion self-management. For further information about health worker roles in abortion care, see Appendix C: World Health Organization recommendations for health worker roles in abortion care.

Resources

Protocols for Medical Abortion (dosage card)

Mifepristone/Misoprostol Gestational Dating Wheels

References

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