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Reproductive Health Supplies Coalition

Ibis Reproductive Health

PRODUC T BRIEF 
Caucus on New and Underused Reproductive Health Technologies
Misoprostol for maternal health
Description
Misoprostol can be used for a number of obstetric 
indications that address maternal health concerns. 
Misoprostol acts as a uterotonic by stimulating strong 
contractions of the uterus and also softens and dilates 
the cervix, similar to the natural process of labor. 
Its uses related to maternal health are many and 
include the prevention and treatment of postpartum 
hemorrhage, labor induction, treatment of incomplete 
abortion and miscarriage, induced abortion, treatment 
of missed abortion, treatment of intrauterine fetal 
death, and cervical ripening before delivery or  
uterine instrumentation. 
Dosing regimens vary depending on the medical 
indication. For labor induction and cervical 
ripening before delivery, the dose can be as low as 
25 mg; however, other indications require a dose of 
between 400 and 800 mg. Recommended routes of 
administration are oral, sublingual, rectal, or vaginal. 
In 2012, the International Federation of Gynecology 
and Obstetrics (FIGO) revised dosage guidelines for 
all obstetric indications.1 Misoprostol is available in 
tablet form, and marketed products typically have a 
shelf life of 18 to 36 months when stored below 25°C  
to 30°C (77°F to 86°F) in a dry area. 
Efficacy 
For the prevention of postpartum hemorrhage 
(PPH): Misoprostol is an effective uterotonic 
in situations where use of oxytocin or other 
injectable uterotonics that require refrigeration and 
administration by a skilled provider is not feasible. 
For these reasons, misoprostol can be especially useful 
in home deliveries. In a multicenter study conducted 
in hospitals, oxytocin performed marginally better 
than oral misoprostol in controlling blood loss.2 
In a study of women delivering at home in India, 
oral misoprostol was associated with a significant 
reduction in the rate of postpartum hemorrhage 
compared to women not using a uterotonic.3 A 
significant reduction in PPH was also observed with 
oral misoprostol when administered by traditional 
birth attendants during home deliveries in Pakistan.4 
The 2012 World Health Organization (WHO) 
recommendations for the prevention and treatment of 
postpartum hemorrhage and the 2012 WHO Priority 
Life-saving Medicines for Women and Children 
state that in settings where oxytocin is unavailable or 
cannot be safely used, the use of oral misoprostol (600 
μg) is recommended for prophylaxis.5,6 WHO’s 17th 
Model List of Essential Medicines includes the use of 
600-μg oral misoprostol for prevention of PPH.7 
For the treatment of PPH: In women who were 
given prophylactic oxytocin as part of the active 
management of the third stage of labor, misoprostol 
and oxytocin were found to be clinically equivalent 
when used to stop excessive postpartum bleeding.8 
In women not exposed to prophylactic oxytocin, 
oxytocin was found to be more effective at controlling 
bleeding within 20 minutes than misoprostol, but 
researchers concluded that 800-mg sublingual 
misoprostol might be a suitable first-line treatment 
in settings in which use of oxytocin is not feasible.9 
WHO recommends the use of a prostaglandin 
drug (including sublingual misoprostol, 800 μg) 
for treatment of PPH if intravenous oxytocin is 
unavailable, or if the bleeding does not respond  
to oxytocin.5
For the treatment of incomplete abortion and 
miscarriage: The efficacy of misoprostol to treat 
incomplete abortion and miscarriage is between 91 to 
99 percent, equivalent to the use of manual vacuum 
aspiration.* Medical management of incomplete 
abortion and miscarriage with misoprostol provides 
a good opportunity to scale up post-abortion care 
* For a complete list of references and discussion, please refer to the Post-abortion care (PAC) Service Delivery Toolkit located at www.vsinnovations.org/
resources.html or  http://www.ipas.org/en/What-We-Do/Comprehensive-Abortion-Care/Elements-of-Comprehensive-Abortion-Care/Medical-Abortion--MA-/
Medical-Abortion--MA--Supply-Guidance/Postabortion-Care-Educational-Resources.aspx.
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services.** WHO’s 17th Model List of Essential 
Medicines and its Priority Life-saving Medicines for 
Women and Children include the use of misoprostol 
for this indication.6,7
For induced abortion***: Effectiveness of 
misoprostol-alone regimens for early-term medical 
abortion range from 76 to 96 percent. Technical 
and policy guidance for health systems, revised 
in 2012, recommends the use of misoprostol for 
induced abortion when mifepristone is not available 
and provides dosage guidelines for pregnancies up 
to 12 weeks gestational age, from 12 to 24 weeks, 
and beyond 24 weeks.10 Though not as effective as 
the combination of mifepristone and misoprostol, 
misoprostol is more widely available than mifepristone 
and has been used safely and successfully for medical 
abortion around the world.11 
For labor induction: Cochrane Reviews have 
concluded that oral misoprostol is more effective 
than placebo and at least as effective as vaginal 
dinoprostone for induction of labor with doses not 
exceeding 50 μg; similarly, while vaginal misoprostol 
is more effective than other conventional methods, 
low-dose oral misoprostol is preferable.12,13 WHO and 
FIGO recommend the use of oral (25 μg, at two-hour 
intervals) or vaginal (25 μg, at six-hour intervals) 
misoprostol for the induction of labor.1,14
Current program/sector use 
In developing countries, programs to introduce or 
expand the use of misoprostol into the health system 
for some obstetric indications are being implemented. 
Misoprostol is included on the national essential 
medicines lists in more than 20 countries.  
WHO recommends that misoprostol can be used by 
community health care workers and lay health workers 
for PPH prevention when skilled birth attendants 
are not present.5 A similar recommendation for lay 
health workers is included in WHO’s 2012 guidelines 
on optimizing health worker roles for maternal 
and neonatal health, though advanced provision of 
misoprostol to pregnant women is deemed a priority 
research area.15
For the prevention of PPH, studies in Afghanistan, 
Bangladesh, and Nepal show that women can use 
misoprostol consistently and safely (even for twin 
deliveries) when the drug is distributed by community 
health workers to women planning to deliver at 
home.16,17,18 Programs in Bangladesh, Ethiopia, Kenya, 
Mozambique, Nigeria, Senegal, Tanzania, Uganda, and 
Zambia have shown that distribution at antenatal care 
visits and by community health workers is effective 
and that misoprostol is used safely and correctly at 
home deliveries.19 Some countries are now taking steps 
to scale up the use of misoprostol for PPH prevention 
in national safe-motherhood programs. 
Pilot PAC programs in Mozambique and Rwanda 
have shown that misoprostol can be safely used as a 
complementary method to manual vacuum aspiration 
(MVA) for treatment of incomplete abortion and 
miscarriage (evacuation of the uterus), particularly at 
lower-level health facilities where the use of MVA may 
not be feasible, or there may not be health workers 
trained in its use.20
In clinical settings globally, misoprostol is commonly 
used off label for induction of labor and cervical 
ripening, and in combination with mifepristone for 
medical abortion, where legally permissible.21 
Manufacturer/supplier 
More than 50 branded and non-branded generic 
versions of 200-mg misoprostol tablets are 
manufactured by pharmaceutical companies in 
high-, middle-, and low-income countries including 
Argentina, Bangladesh, Brazil, Chile, China, Egypt, 
France, India, Mexico, Pakistan, Peru, Russia, 
South Korea, and the United States.22 Some of these 
manufacturers are making products for export to 
low- and middle-income countries, but many only 
make products for their local markets. Cytotec® 
(manufactured by Pfizer) is the most widely available 
misoprostol product. The few manufacturers of 
the 25-mg tablet include Cipla Pharmaceuticals 
(India), Adwia Pharmaceuticals (Egypt), and Hebron 
Pharmaceuticals (Brazil).
Misoprostol is eligible for the WHO’s Prequalification 
of Medicines Programme, but no product is yet 
prequalified.23 As part of its Quality Assurance 
Policy for Reproductive Health Medicines, the 
United Nations Population Fund (UNFPA) has 
set up an Expert Review Panel (ERP) to assess 
whether reproductive health products (including 
misoprostol) from manufacturers that apply for 
** Further information on the treatment of incomplete abortion with misoprostol and service delivery guidelines for integrating misoprostol into PAC 
services can be found at http://vsinnovations.org/resources.html or http://www.ipas.org/ma/mpactoolkit and http://gynuity.org/resources/info/guidebook-on-
misoprostol-for-treatment-of-incomplete-abortion/.
*** For more information on misoprostol for induced medical abortion, please see the Caucus brief Mifepristone and Misoprostol for on Medical Abortion.
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WHO prequalification could be recommended for 
use before achieving prequalification.24 A product 
made by Exelgyn (France) has passed the ERP process, 
but is only registered for use with mifepristone for 
termination of pregnancy. Efforts are underway to 
provide technical assistance to generic manufacturers 
of misoprostol products that can be registered for 
other obstetric indications, with the aim of building 
their capacity to pass the ERP process and achieve 
WHO prequalification.25 
Registration status 
Registration, or market approval of a drug by a 
country’s drug regulatory agency, grants permission 
for a product from a specific manufacturer to be 
marketed in that country by a pharmaceutical 
distributor for the medical indications for which 
the application was made. The registration status of 
misoprostol varies. Misoprostol is most commonly 
registered for prevention and treatment of gastric 
ulcers; Cytotec® is registered in more than 80  
countries for these two indications. In many  
countries, misoprostol may be legally used off label  
for obstetric indications. 
Misoprostol is increasingly being registered for 
obstetric indications. Exporting manufacturers that 
have registered products for obstetric indications, 
mostly in sub-Saharan Africa and South Asia, include 
Acme Formulations (India), Cipla Pharmaceuticals 
(India), Sigma Pharmaceuticals (Egypt), Square 
Pharmaceuticals (Bangladesh), Zizhu Pharmaceuticals 
(China), and Fourtts Laboratories (India), and there 
are likely to be others. 
Products are registered for obstetric indications in 
more than 20 countries, including Bangladesh, Bolivia, 
Cambodia, Ethiopia, India, Kenya, Malawi, Mali, 
Mozambique, Myanmar, Nepal, Pakistan, Senegal, 
Somaliland, Sudan, Tanzania, Uganda, and Zambia. 
More registrations are expected in the coming years 
in response to increasing demand. The approved 
indications vary across countries; in some countries, 
products are only registered for PPH prevention 
and treatment, while in others they are registered 
for multiple obstetric indications. The indications 
for which the drug is granted approval usually 
depend on the level of commitment and willingness 
of governments to integrate misoprostol into safe-
motherhood programs. More information on the 
global status of misoprostol registration can be found 
at http://www.vsinnovations.org/resources.html.
Public-sector price agreements
There are no global public-sector price agreements for 
misoprostol. Governments can purchase a misoprostol 
product that is registered in their country and can 
negotiate the price with the distributor that holds the 
market approval. 
References
1. International Federation of Gynecology and Obstetrics 
(FIGO). Misoprostol Safe Dosage Guidelines. United 
Kingdom: FIGO; 2012. Available at: http://www.figo.org/
publications/miscellaneous_publications/Misoprostol_
Recommendation_2012.
2. Gülmezoglu AM, Villar J, Ngoc NT, et al. WHO multicentre 
randomised trial of misoprostol in the management of the 
third stage of labour. The Lancet, 2001;358(9283):689–95.
3. Derman RJ, Kodkany BS, Goudar SS, et al. Oral misoprostol 
in preventing postpartum haemorrhage in resource-poor 
communities: a randomised controlled trial. The Lancet. 
2006;368:1248–1253.
4. Mobeen N, Durocher J, Zuberi N, et al. Administration of 
misoprostol by trained traditional birth attendants to prevent 
postpartum haemorrhage in homebirths in Pakistan: a 
randomised placebo-controlled trial. BJOG 2011;118(3):353–
361.
5. World Health Organization (WHO). WHO Recommendations 
for the Prevention and Treatment of Postpartum Hemorrhage. 
Geneva: WHO; 2012. Available at: http://www.who.int/
maternal_child_adolescent/documents/postpartum_
haemorrge/en/index.html. 
6. WHO. Priority Life-saving Medicines for Women and Children 
2012. Geneva: WHO; 2012. Available at: http://www.who.int/
medicines/publications/emp_mar2012.1/en/index.html.
7. WHO. Model List of Essential Medicines (17th Edition). Geneva: 
WHO; 2011. Available at: http://whqlibdoc.who.int/hq/2011/
a95053_eng.pdf. 
8. Blum J, Winikoff B, Raghavan S, et al. Treatment of post-
partum haemorrhage with sublingual misoprostol versus 
oxytocin in women receiving prophylactic oxytocin: a 
double-blind, randomised, non-inferiority trial. The Lancet. 
2010;375(9710):217–223. 
9. Winikoff B, Dabash R, Durocher D, et al. Treatment of post-
partum haemorrhage with sublingual misoprostol versus 
oxytocin in women not exposed to oxytocin during labour: a 
double-blind, randomised, non-inferiority trial. The Lancet. 
2010;375(9710):210–216.
10. WHO. Safe Abortion: Technical and Policy Guidance for 
Health Systems (second edition).  Geneva: WHO; 2012. 
Available at: http://www.who.int/reproductivehealth/
publications/unsafe_abortion/9789241548434/en/.  
11. Faundes A, et al. Misoprostol for the termination of pregnancy 
up to 12 completed weeks of pregnancy. International Journal 
of Gynecology & Obstetrics. 2007;99(2):S172–177.
12. Alfirevic Z, Weeks A. Oral misoprostol for induction of labour. 
Cochrane Database of Systematic Reviews. 2006;2:CD001338.
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This brief was last updated May 2013
4
For more information on the Caucus on New and Underused RH Technologies, please visit our web page at  
http://www.rhsupplies.org/working-groups/caucus-on-newunderused-rh-technologies.html.
This publication forms part of a series of technical briefs, written by members of the Caucus on New and Underused Reproductive Health 
Technologies, a thematic group established under the auspices of the Reproductive Health Supplies Coalition. The Caucus’ aim is to 
broaden the discussion within the Coalition of reproductive health technologies that are not well integrated into the public or commercial 
health sectors. Responsibility for the selection and contents of the product briefs rests solely with the Caucus and does not imply 
endorsement by the Coalition or its wider membership. For additional information, please contact secretariat@rhsupplies.org.
13. Hofmeyr GJ, Gülmezoglu AM, Pileggi C. Vaginal misoprostol 
for cervical ripening and induction of labour. Cochrane 
Database of Systematic Reviews. 2010;10:CD000941.
14. WHO. Recommendations for Induction of Labour. Geneva: 
WHO; 2011. Available at: http://whqlibdoc.who.int/
publications/2011/9789241501156_eng.pdf. 
15. WHO. Optimizing Health Worker Roles to Improve Access 
to Key Maternal and Newborn Health Interventions Through 
Task Shifting. Geneva: OptimizeMNH, WHO; 2012. Available 
at: http://www.optimizemnh.org/. 
16. Sanghvi H, Ansari N, Prata JVN, Gibson H, Ehsan A, Smith 
J. Prevention of postpartum hemorrhage at home birth 
in Afghanistan. International Journal of Gynecology and 
Obstetrics. 2010;108:276–281.
17. Rajbhandari S, Hodgins S, Sanghvi H, et al. Expanding 
uterotonic protection following childbirth thought 
community-based distribution of misoprostol: operations 
research in Nepal. International Journal of Gynecology and 
Obstetrics. 2010;108:282–288.
18. Nasreen HE, Nahar S, Mamun M, Afsana K, Byass P. Oral 
misoprostol for preventing postpartum haemorrhage in home 
births in rural Bangladesh: how effective is it? Global Health 
Action. 2011;4:7017.
19. Prata N, Mbaruku G, Campbell M, Potts M, Vahidnia F. 
Controlling postpartum hemorrhage after home births in 
Tanzania. International Journal of Gynecology & Obstetrics. 
2005;90:51–55.
20. Sahin-Hodoglugil N, Graves A and Prata N. The role of 
misoprostol in scaling up postabortion care. International 
Perspectives on Sexual and Reproductive Health. 2011;37(3):158.
21. Weeks AD, Fiala C, Safar P. Misoprostol and the debate over 
off-label drug use. BJOG. 2005;112(3):269–272.
22. Fernandez MM, et al. Assessing the Global Availability 
of Misoprostol. International Journal of Gynecology and 
Obstetrics. 2009;105:180–186.
23. WHO Prequalification of Medicines Programme website. 
Available at: http://apps.who.int/prequal. 
24. United Nations Population Fund (UNFPA). Quality Assurance 
Policy for Reproductive Health Medicines. New York: UNFPA; 
2012.  Available at: http://www.unfpa.org/public/home/
procurement/pid/10865.
25. Concept Foundation. Quality of Reproductive Health Medicines 
Program. Available at: http://www.conceptfoundation.org/
business.php. 


Misoprostol for maternal health

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Misoprostol for maternal health

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