PRODUCT BRIEF Caucus on New and Underused Reproductive Health Technologies

Mifepristone and misoprostol for medical abortion

Description Complete abortion rates in early pregnancy with misoprostol-only regimens range from 76 to 96 percent, Medical abortion (MA) is a nonsurgical procedure in according to existing research.4,5,6 Even though the which drugs are used to induce abortion. The most combined regimen of mifepristone followed by misoprostol effective and safest medical abortion regimen requires the is significantly more effective than use of misoprostol use of two medications: mifepristone and misoprostol. alone for early MA, misoprostol is generally more widely Mifepristone blocks the action of progesterone to available than mifepristone and has been used alone enhance the contractility of the uterus and prompt safely and successfully for MA around the world.7 When the detachment of the implanted embryo. Misoprostol mifepristone is unavailable, the International Federation of stimulates strong contractions of the uterus, expelling the Gynecology and Obstetrics (FIGO) and WHO recommend products of conception. This process is very similar to vaginal or sublingual administration of 800-μg misoprostol that of a spontaneous abortion or miscarriage.1 Repeated in pregnancies up to 12 weeks of gestation, repeated three administration of misoprostol alone can also be used to times every 3 to 12 hours. For pregnancies of 12 to induce abortion. Both drugs also soften and dilate 24 weeks of gestation, the dose is halved and can be the cervix. repeated up to five times every three hours.8 Quality abortion care should include counseling, The use of mifepristone and misoprostol is very safe; MA confirmation of intra-uterine pregnancy, and estimation has not been associated with long-term health impacts and of gestational age by the patient’s history, bimanual exam, is statistically less risky than continuation of pregnancy.9 or with ultrasound—although the latter is not required. MA may be preferable to surgical abortion for some Family planning and contraception counseling should women and their providers, as it is less invasive and can be be provided at the time of the abortion or afterwards. perceived to be a more private procedure by some women. Medical abortion options have made abortion more available to women in a variety of health care settings, and home administration of medical abortion is also Current program/sector use highly acceptable.2 There are a number of political, logistical, cultural, religious, financial, and other barriers that limit universal Efficacy access to MA. Elective abortion is legally restricted in many countries, but almost all countries have provisions under The 2012 World Health Organization (WHO) publication which abortion is legal, including to save the woman’s life, “Safe Abortion: Technical and Policy Guidance for Health to preserve physical or mental health, when the pregnancy Systems” contains guidelines for the use of mifepristone is a result of rape or incest, or on socioeconomic grounds. and misoprostol for MA up to nine weeks, 9 to 12 weeks, Where abortion is legal, challenges may arise in terms of and after 12 weeks of gestation.3 All the regimens use health-system restrictions on where the services can be 200 mg of mifepristone followed by 800 μg of misoprostol provided, procurement of the drugs, and provider training administered vaginally, buccally, or sublingually. The to properly inform and counsel patients about their misoprostol dose is taken 24 to 48 hours after mifepristone options. However, MA is being made available to women for pregnancies up to gestational age of 9 weeks, and 36 to in numerous countries, including some sub-Saharan 48 hours later for pregnancies of 9 to 12 weeks African countries. The level of use in developed countries in gestational age and beyond 12 weeks. Additional such as the United States and those in Europe suggests 400-μg doses of misoprostol may be required depending on that women appreciate having an alternative to surgical gestational age. These regimens result in complete abortion abortion; women in Europe have been using mifepristone in more than 95 percent of cases; the rate of continuing and misoprostol for more than 20 years. pregnancy is less than 1 percent in gestations up to 63 days’ amenorrhea. CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF Many more branded and non-branded generic versions Linepharma’s product was registered inKenya in2012. France), are available inmostly high-income countries. France), and anon-branded generic (Linepharma, Laboratories, USA)and (Laboratoire Mifegyne® Exelgyne, Two branded generics of mifepristone, Mifeprex® (Danco Mifepristone (mifepristone, misoprostol, and combination packs). There are numerous manufacturersthree all of products and incombination for packs made specifically MA. manufacturers, as individually packaged medicines, Mifepristone and misoprostol are available from generic Manufacturer/supplier *** For more information on misoprostol, Caucus the brief on see please Misoprostol for Maternal Health. misoprostol-for-treatment-of-incomplete-abortion/. found can be atservices http://vsinnovations.org/resources.html or http://www.ipas.org/ma/mpactoolkit and http://gynuity.org/resources/info/guidebook-on- ** Further information on treatment the of incomplete abortion with misoprostol guidelines for delivery integrating and service misoprostol into PAC Medical-Abortion--MA--Supply-Guidance/Postabortion-Care-Educational-Resources.aspx resources.html or http://www.ipas.org/en/What-We-Do/Comprehensive-Abortion-Care/Elements-of-Comprehensive-Abortion-Care/Medical-Abortion--MA-/ * For acomplete list of references and discussion, refer please to Post-abortion the care (PAC) Toolkit Delivery Service located at www.vsinnovations.org/ only. Medabon®, acombination pack manufactured by Sun andin China India and are market for local inthe use middle-income countries. Most of products these are made are currently only made by manufacturers inlow- and (200 mg) and four tablets of misoprostol (200μgeach) Combination packs containing one tablet of mifepristone Mifepristone-misoprostol combination packs programs.these provide assistance technical to manufacturers applying to achieving prequalification. prequalificationbe could recommended beforefor use products from manufacturers that are applying for WHO Panel process, assess misoprostol whether will which United Nations Population Fund (UNFPA) Review Expert Prequalification of Medicines Programme, widely available. Misoprostol is eligible for WHO the first misoprostol product the on market andthe is most (Pfizer), registered in morethan 80countries,the was only make products for markets. local their Cytotec® income countries; however, as with mifepristone, many are making products for to low- export and middle- and United the States. France,Egypt, India, Mexico, Peru, South Korea, Russia, including Argentina, Bangladesh, Brazil, China, Chile, companies and middle-, inhigh-, low-income countries, of misoprostol are manufactured by pharmaceutical More than 50branded and non-branded generic versions Misoprostol India and but China, capacity export their is limited. companies inlow- and middle-income countries such as of mifepristone are made by numerous pharmaceutical 13 10 Some of manufacturers these 12 Efforts are to underway 11 and for the for breadth the of for uses are they which effective, and care health officials to ensuredrugs both are registered international organizations are working with policymakers acceptable, up to nine weeks of gestation. Medicines for termination of pregnancy where and legal for MAwas included on WHO the Model List of Essential combination2005, the of mifepristone and misoprostol for anumber of obstetric indications, including MA.**In existing supporting evidence misoprostol’s effectiveness prevention of ulcers. This gastric is despite a breadth of products are only registered for treatment the and around world, the but inalarge number of countries those Misoprostol products are registered inmost countries Registration status generic manufacturers of product. the and efforts are to underway support applicationsfrom for WHO’s the Prequalification of Medicines Programme, The mifepristone and misoprostol combination is eligible packs as interest grows globally. manufacturers Other export.* may combination export Formulations (India) makes aproduct also available for Pharmaceuticals (India) is available for and export, Acme with mifepristone for abortion. medical other countries, misoprostol is prescribed offlabel for use (registered by Pentcroft Pharma as Misoprostol). In many France (registered by Pharma HRA as Gymiso®) and Russia for with mifepristone use for pregnancy termination in Mozambique. only afew countries, including Ethiopia, Ghana, and Misoprostol products have approved been for MAin Registration of misoprostol for MAis far from universal. Misoprostol with misoprostol. others it is registered of as part acombination pack countries,these mifepristone is registered alone and in Mozambique, Nepal, Vietnam, and Zambia. registered are Ghana, Cambodia, India, Kenya, low-income countries where mifepristone is currently abortion in50countriesin medical worldwide; the Mifepristone registered has been and approved for use Mifepristone registration status for and each drug combination the pack. including MA.The informationbelow global the highlights 16 *** Misoprostol registered has been specifically

14 Anumber of 15 In some of

2 CAUCUS ON NEW AND UNDERUSED REPRODUCTIVE HEALTH TECHNOLOGIES PRODUCT BRIEF The ConceptThe Foundation has negotiated a preferential price Public-sector price agreements available for export. combination packs are registered for MA,but are they not sub-Saharan In Africa. India, many brands of Indian-made from other manufacturers other countries inseveral in and efforts are to underway register combinationpacks Acme Formulations registered is also inMozambique, and 14countries inEurope. Acombination product from Ghana,Cambodia, India, Mozambique, Nepal, Zambia, Medabon® is currently registered for abortion in medical Mifepristone-misoprostol combination packs endorsement by theCoalition orits wider membership. For additional information, please contact health sectors. Responsibility for theselectionand contents of theproduct briefs rests solely with theCaucus and does not imply broaden thediscussion within theCoalition of reproductive health technologies that are not well integrated into thepublic orcommercial Technologies, athematic group established under theauspices of theReproductive Health Supplies Coalition. The Caucus’ aimis to This publication forms part of aseries of technical briefs, written by members of theCaucus onNewand Underused Reproductive Health http://www.rhsupplies.org/working-groups/caucus-on-newunderused-rh-technologies.html For more information ontheCaucus onNewand Underused RHTechnologies, please visit our web page at 4. 3. 2. 1. References often dependent upon product demand. Pricing varies by manufacturer, and is country-specific, is is large,drugs and market the is continuing to evolve. countries. number the Overall, of manufacturers for these for public-sector procurement of Medabon® indeveloping Reproduction misoprostolvaginal before and afterdays 42 gestation. KA,Zikopoulos etal. Early pregnancy termination with unsafe_abortion/9789241548434/en/. at: http://www.who.int/reproductivehealth/publications/ Guidance for Health Systems World Health Organization. Contraception administration of misoprostol for abortion. medical of significant factors affecting acceptability of home Kopp C,Gemzell-Danielsson Kallner K.Assessment H,Fiala Early First Trimester, Bellagio, Italy International Consensus Conference on Medical Abortion in Clinical Questions About Medical Abortion: Conclusions of an World Health Organization (WHO). . 2002;17(12):3079–3083. . 2011;85(4):394–397. . Geneva: WHO;. Geneva: 2012.Available Safe Abortion: Technical and Policy . Geneva: WHO;. Geneva: 2006. Frequently Asked Human Human 12. 11. 10. 9. 8. 7. 6. 5. 16. 15. 14. 13. Policy for Reproductive Health Medicines United Nations Population Fund (UNFPA). ReproductiveHealth-V5.pdf. at: http://apps.who.int/prequal/info_applicants/eoi/EOI_ Prequalification Programme, WHO;Geneva: 2010. Available of Interest (EOI) for product evaluation to WHO the of reproductive products health to submit an Expression World Health Organization. Invitation 5th to manufacturers 2009;105:180–186. misoprostol. Fernandez MM,etal. Assessing availability global the of Journal of Obstetrics and Gynecology by pregnancy outcome, United States, 1991to 1999. Grimes DA. Estimation of pregnancy-related mortality risk Misoprostol_Recommendation_2012. www.figo.org/publications/miscellaneous_publications/ Recommendations Misoprostol International Federation and of Gynecology Obstetrics. of Gynecology &Obstetrics up to 12completed weeks of pregnancy. Faundes A,etal. Misoprostol for termination the of pregnancy Gynecology trimester abortion: arandomized controlled trial. misoprostol compared with misoprostol alone for second- Ngoc NT, Shochet T, Raghavan S,etal. Mifepristone and evacuation. by 800[mu]g single-dose misoprostol compared with surgical Prasad S,AKumar, Early ADivya. termination of pregnancy www.vsinnovations.org/resources.html. approval page. updated Last January 2013.Available at: http:// Venture Strategies Innovations website. Map of misoprostol info/list-of-mifepristone-approval/. September 2012.Available at: http://gynuity.org/resources/ Gynuity website. List of mifepristone approvals. updated Last essentialmedicines/en/. Available at: http://www.who.int/medicines/publications/ World Health Organization. business.php. Program Concept Foundation. procurement/pid/10865. 2012. Available at: http://www.unfpa.org/public/home/ . Available at: http://www.conceptfoundation.org/ . 2011;118(3):601–608. Fertility and Sterility International Journal of Gynecology and Obstetrics [email protected] Quality of Reproductive Health Medicines . 2007;99(2):S172–177. Model Lists of Essential Medicines . 2012.Available at: http:// . 2009;91(1):28–31. This brief was last updated May 2013 May updated waslast brief This . 2006;194(1):92–94. . New York: UNFPA; International Journal International Journal . Quality Assurance Quality . Obstetrics & American American

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