MIFEPRISTONE WITH MISOPROSTOL REGIMENS
- Mifepristone, in a regimen with misoprostol, was approved by the FDA for abortion in 2000; The label was updated in 2016 to reflect best practices at the time and facilitate improved efficacy, safety, convenience, and side effects.
- Recent data has demonstrated high rates of success of mifepristone 200mg and misoprostol 800 mcg followed by a 2nd dose of misoprostol 4 hours later, at 63-70 days, as well as 70-77 days gestational age (NAF CPG 2020, Dzuba 2020).
- In light of COVID-19, many organizations moved rapidly to no test and minimum contact implementation. Sample protocols below can be adapted for practice setting.
Evidence-Based Mifepristone Regimens
Based on evidence up to 2020, Partially adapted from NAF Clinical Practice Guidelines 2020
|Gestational Age||Mifepristone Dose (Day 1)6||Misoprostol Dose & Route||Efficacy||Core References|
Mifepristone 200mg PO
|Misoprostol 800 mcg buccal, vaginal1, 2 or sublingual3 24-48 hours after mifepristone||95-99%||Creinin 2004, 2007 Schaff 1999, 2002 Ashok 1998, Middleton 2005, Chai 2013, Tang 2003, Gatter 2015|
|64 – 70 days||Consider 2nd misoprostol 800mcg
4 hours after 1st dose for patients over 63 days
|Danco 2016, Chen 2015, Bracken 2014, Winikoff 2012, Boersma 2011, Sanhueza Smith 2015, Hsia 2019, Dzuba 2020|
|71 – 77 days4, 5||Recommend 2nd misoprostol 800mcg
4 hours after 1st dose for patients >70 days
|Dzuba 2016, Dzuba 2020, Larsson 2019, Kapp 2019|
- Vaginal route enables wider time frame for use of misoprostol, 0-72 hours after mifepristone, with highest efficacy rates between 24-48 hours.
- Primary studies demonstrating efficacy from 64-70 days used buccal and sublingual misoprostol regimens; updated evidence confirms similar efficacy with vaginal route in this gestational age range (Hsia 2019).
- Sublingual misoprostol dose range 400-800mcg. Fewer side effects shown with lower dose though may have lower efficacy rates (Von Hertzen 2010).
- Medication abortion at 71-77 days LMP is evidence-based, and success rates in the late first trimester are higher with repeat misoprostol doses (Kapp 2019, Dzuba 2020).
- Protocols > 77 days, used in some global settings, tend to require multiple doses of misoprostol (Hamoda 2003,2005; Lokeland 2010, Kapp 2019, Ipas 2020, WHO 2018).
- Ongoing studies are evaluating telehealth protocols that mail mifepristone in the U.S. and abroad.
- Misoprostol-only is a reasonable alternative to mifepristone-containing regimens when mifepristone is not available, though it is less effective (Blum 2012, Kulier 2011). The recommended regimen consists of misoprostol 800 mcg buccally, vaginally, or sublingually with repeated doses as needed for success. (Sheldon 2019, Raymond 2019, Gynuity 2013, Von Hertzen 2007).
- Misoprostol is available by prescription in U.S. or over the counter in some countries.
- In global locations with restrictive laws or poor mifepristone access, misoprostol alone has been used for early abortion in clinical settings as well as in SMA (Stillman 2020). SMA increases in times of threatened access as during the COVID-19 pandemic.
- More information about self-managed abortion safety and access is available in Chapter 3, and World Health Organization, Aid Access and Women on Web.
|Gestational Age||Misoprostol Dose & Route||Efficacy||Core References|
|Less than or equal to 63 days||Misoprostol 800 mcg vaginal, sublingual1, or buccal every 3 hours x 3 doses until expulsion||84-96%||Moreno-Ruiz 2007, Von Hertzen 2007
Gynuity 2013, Ipas 2020, WHO 2018
|64 – 70 days||As above.
Additional doses may be used if bleeding does not start.
93% with 4th dose
|Sheldon 2019, Ipas 2020, WHO 2018|
|Up to 91 days||75-81%||Raymond 2019, Kapp 2019,
Ipas 2020, WHO 2018
- Increased efficacy demonstrated with sublingual compared to buccal misoprostol in misoprostol-only regimens through 70 days gestation, though with increased incidence of side effects (Sheldon 2019).
Methotrexate 50 mg/m2 is used for ectopic pregnancy or can be combined with misoprostol when diagnosis is indeterminate and patient has chosen not to be managed by diagnostic aspiration. Unlike mifepristone, methotrexate is an effective treatment for early unruptured ectopic pregnancy. Success is determined with serial hCG testing, clinical exam and improvement of signs and symptoms (Seeber 2006).