Clinical Updates in Reproductive Health

Mifepristone and misoprostol: Recommended regimen

Last reviewed: February 7, 2021

Recommendation:

  • Up to 10 weeks gestation (70 days since last menstrual period (LMP)): Mifepristone 200mg orally followed 1-2 days later by misoprostol 800mcg buccally, sublingually or vaginally.
  • 10-13 weeks gestation: Following mifepristone, women typically require two doses of misoprostol for a successful abortion.
      • Mifepristone 200mg orally followed 1-2 days later by either misoprostol 600mcg sublingually or 800mcg vaginally, then 400mcg sublingually or vaginally every three hours until expulsion.
      • Alternatively, mifepristone 200mg orally followed 1-2 days later by misoprostol 800mcg buccally, sublingually or vaginally may be used; the dose of misoprostol may be repeated to achieve abortion success.

Strength of recommendation: Strong

Quality of evidence:

  • Up to 10 weeks gestation: High
  • 10-13 weeks gestation: Low

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, Shannon, Weaver, & Winikoff, 2012). Vaginal, buccal and sublingual misoprostol are more effective than oral misoprostol (Kulier et al., 2011). Buccal dosing (Middleton et al., 2005) and sublingual dosing (Tang, Chan, Ng, Lee, & Ho, 2003; von Hertzen et al., 2010) have higher rates of gastrointestinal side effects than vaginal dosing. 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 women’s preferences or legal restrictions.

Simultaneous dosing of mifepristone and misoprostol in women 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, Mittal, Taneja, Singal, & Attri, 2011; Lohr, Starling, Scott, & Aiken, 2018). 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).

9-10 weeks (64-70 days since LMP)

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 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). Further, there were no differences in serious adverse events, such as hospital admissions or transfers, between the groups (0.7% and 0.5% respectively). One observational study included in the review reported an abortion success rate of 94.5% from 9-10 weeks when women used a regimen of mifepristone followed by 800mcg of vaginal misoprostol (Gouk et al., 1999). Additional studies published since this review using sublingual (Platais, Tsereteli, Grebennikova, Lotarevich, & Winikoff, 2016) or buccal misoprostol (Tan et al., 2018) after mifepristone have shown similar success rates for the gestational age range from 9-10 weeks.

10-13 weeks

A retrospective cohort study of 1,076 women showed that a combination of 200mg mifepristone followed 36-48 hours later by misoprostol (800mcg vaginally or 600mcg sublingually), and then repeated doses of 400mcg misoprostol vaginally or sublingually every three hours for two additional doses is safe and effective between 9-13 weeks (Hamoda, Ashok, Flett, & Templeton, 2005). All women took misoprostol in the health facility. The success rate for this regimen was high at 95.8%, with a low rate of serious adverse events. A smaller trial randomized 211 women with pregnancies between 9-13 weeks to either the vaginal or sublingual route of misoprostol administration described above; all women received pretreatment with mifepristone (Hamoda, Ashok, Flett, & Templeton, 2005a). In both groups, women typically required 2 doses of misoprostol to have a successful abortion; 3.4% of women in the vaginal group required surgical evacuation of the uterus, compared to 2.9% in the sublingual group. Women in the sublingual group were more likely to experience side effects. A  prospective cohort study (Lokeland et al., 2010) including 254 women reported an abortion success rate of 91.7% using a similar regimen. A small prospective cohort study examined effectiveness of mifepristone 200mg orally followed 36-48 hours later by misoprostol 800mcg vaginally as a single dose (Gouk et al., 1999), and found a success rate of 95% among 126 women with pregnancies between 70-83 days. 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., 2020). The expulsion 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, leading investigators to conclude that an abortion regimen with a single dose of misoprostol after 70 days is less effective. A 2018 systematic review of medical abortion in the late first trimester concluded that abortion success rates are higher when routine, repeated doses of misoprostol are used and when the vaginal route is used over oral administration (Kapp, Eckersberger, Lavelanet, & Rodriguez, 2018).

Resources

Protocols for Medical Abortion (dosage card)

Mifepristone/Misoprostol Gestational Dating Wheels

References

Abbas, D., Chong, E., & Raymond, E. G. (2015). Outpatient medical abortion is safe and effective through 70 days gestation. Contraception, 92(3), 197-199.

Abubeker, F. A., Lavelanet, A., Rodriguez, M.I. &  Kim, C. (2020). Medical termination for pregnany in early first timester (≤63 days) using combination of mifepristone and misoprostol alone: a systematic review. BMC Women’s Health, 20, 142.

Boersma, A. A., Meyboom-de Jong, B., & Kleiverda, G. (2011). Mifepristone followed by home administration of buccal misoprostol for medical abortion up to 70 days of amenorrhea in a general practice in Curacao. European Journal of Contraception & Reproductive Health Care, 16(2), 61-66.

Bracken, H., Dabash, R., Tsertsvadze, G., Posohova, S., Shah, M., Hajri, S., … Winikoff, B. (2014). A two-pill sublingual misoprostol outpatient regimen following mifepristone for medical abortion through 70 days’ LMP: A prospective comparative open-label trial. Contraception, 89(3), 181-186.

Chai, J., Wong, C. Y. G., & Ho, P. C. (2013). A randomized clinical trial comparing the short-term side effects of sublingual and buccal routes of misoprostol administration for medical abortions up to 63 days’ gestation. Contraception, 87(4), 480-485.

Chen, M. J., & Creinin, M. D. (2015). Mifepristone with buccal misoprostol for medical abortion: A systematic review. Obstetrics & Gynecology, 126(1), 12-21.

Creinin, M. D., Schreiber, C. A., Bednarek, P., Lintu, H., Wagner, M. S., Meyn, L. A., & Medical abortion at the same time (MAST) study group. (2007). Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: A randomized controlled trial. Obstetrics & Gynecology, 109, 885-894.

Goel, A., Mittal, S., Taneja,, B. K., Singal, N., & Attri, S. (2011) Simultaneous administration of mifepristone and misoprostol for early termination of pregnancy: A randomized controlled trial. Archives of Gynecology and Obstetrics, 283, 1409-13.

Gouk, E. V., Lincoln, K., Khair, A., Haslock, J., Knight, J., & Cruickshank, D. J. (1999). Medical termination of pregnancy at 63-83 days gestation. BJOG: An International Journal of Obstetrics & Gynaecology, 106, 535-539.

Hamoda, H., Ashok, P. W., Flett, G. M., & Templeton, A. (2005). Medical abortion at 9-13 weeks’ gestation: A review of 1076 consecutive cases. Contraception, 71(5), 327-332.

Hamoda, H., Ashok, P. W., Flett, G. M., & Templeton, A. (2005a). A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation. BJOG: An International Journal of Obstetrics & Gynaecology, 112, 1102-1108.

Kapp, N., Baldwin, M. K., & Rodriguez, M. I. (2018). Efficacy of medical abortion prior to 6 gestational weeks: A systematic review. Contraception, DOI: 10.1016/j.contraception.2017.09.006.

Kapp, N., Eckersberger, E., Lavelanet, A., & Rodriguez, M. I. (2019). Medical abortion in the late first trimester: a systematic review. Contraception, 99(2), 77-86.

Kulier, R., Kapp, N., Gulmezoglu, A. M., Hofmeyr, G. J., Cheng, L., & Campana, A. (2011). Medical methods for first trimester abortion. The Cochrane Database of Systematic Reviews (11), CD002855.

Lohr, P. A., Starling, J. E., Scott, J. G., & Aiken, A. R. A. (2018). Simultaneous compared with interval medical abortion regimens where home use is restricted. Obstetrics & Gynecology, 131(4), 635-641.

Lokeland, M., Iverson, O. E., Dahle, G. S., Nappen, M. H., Ertzeid, L., & Bjorge, L. (2010). Medical abortion at 63 to 90 days of gestation. Obstetrics & Gynecology, 115(2), 962-968.

Middleton, T., Schaff, E., Fielding, S. L., Scahill, M., Shannon, C., Westheimer, E., & Winikoff, B. (2005). Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception, 72(5), 328-332.

Pena, M., Dzuba, I. G., Smith, P. S., Mendoza, L. J., Bousieguez, M., Martinez, M. L., … Winikoff, B. (2014). Efficacy and acceptability of a mifepristone-misoprostol combined régimen for early induced abortion among women in Mexico City. International Journal of Gynecology & Obstetrics, 127(1), 82-85.

Platais, I., Tsereteli, T., Grebennikova, G., Lotarevich, T., & Winikoff, B. (2016). Prospective study of home use of mifepristone and misoprostol for medical abortion up to 10 weeks of pregnancy in Kazakhstan. International Journal of Gynecology & Obstetrics, 134 (3), 268-271.

Raghavan, S., Tesereteli, T., Kamilov, A., Kurbanbekova, D., Yusupov, D., Kasimova, F., … Winikoff, B. (2013). Acceptability and feasibility of the use of 400mcg of sublingual misoprostol after mifepristone for medical abortion up to 63 days since the last menstrual period: Evidence from Uzbekistan. The European Journal of Contraception and Reproductive Health Care, 18(2), 104-111.

Raymond, E. G., Shannon, C., Weaver, M. A., & Winikoff, B. (2012). First-trimester medical abortion with mifepristone 200 mg and misoprostol: A systematic review. Contraception, 87(1), 26-37.

Sanhueza Smith, P., Pena, M., Dzuba, I. G., Garcia Martinez, M. L., Aranqure Peraza, A. G., Bousiequez, M., … Winikoff, B. (2015). Safety, efficacy and acceptability of outpatient mifepristone-misoprostol medical abortion through 70 days since last menstrual period in public sector facilities in Mexico City. Reproductive Health Matters, 22(44 Suppl 1), 75-82.

Tang, O.S., Chan, C.C.W., Ng, E., Lee, S.W.H., & Ho, P.C. (2003) A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation. Human Reproduction, 18(11), 2315–2318.

von Hertzen, H., Huong, N. T., Piaggio, G., Bayalag, M., Cabezas, E., Fang, A. H., & Peregoudov, A. (2010). Misoprostol dose and route after mifepristone for early medical abortion: A randomised controlled noninferiority trial. BJOG: An International Journal of Obstetrics & Gynaecology, 117(10), 1186-1196.

Winikoff, B., Dzuba, I. G., Chong, E., Goldberg, A. B., Lichtenberg, E. S., Ball, C., … Swica, Y. (2012). Extending outpatient medical abortion services through 70 days of gestational age. Obstetrics & Gynecology, 120(5), 1070-1076.