Misoprostol: An evidence-based technology for PPH

1. Misoprostol: An evidence-based technology for PPH Jill Durocher, Gynuity Health Projects, New York, USA SOGC Event, 3 November 2008 Ottawa, Canada

2. What is misoprostol? • Prostaglandin E1 analogue • Developed for prevention and treatment of gastric ulcers • Off patent 1992 • Use for variety of RH indications • Causes contractions of the uterus, reduces bleeding, opens cervix, empties uterus

3. Advantages of Misoprostol • Safe • Evidence-based • Easy to transport and store (no cold chain required) • Oral administration • Inexpensive • Widely available • Few contra-indications

4. Why misoprostol for PPH? • PPH is leading cause of maternal death MMR due to PPH ~30% • Conventional uterotonics for PPH prevention and treatment are largely unavailable ornot feasible • When a PPH occurs, treatment needed quickly to control bleeding: women may die within one hour, leaving little time for transportation to higher levels of care • To meet Millennium Development Goals, urgently needed at all levels: easier to use, available, low cost prevention/treatment options that require few skills

6. Misoprostol Prophylaxis: Community-Based Evidence India – primary health centers/home births, nurse-midwives • 600 mcg oral misoprostol associated with 50% reduction in PPH (Derman et al 2006) The Gambia – home births, traditional birth attendants • 600 mcg oral misoprostol associated with statistically significant smaller drop in hemoglobin (Walraven 2005) Guinea-Bissau – primary health centers, midwives 600 mcg sublingual misoprostol associated with significant reduction in severe PPH (Hoj 2005)

7. Misoprostol Prophylaxis:Current Recommendations • Active management of the third stage of labor (AMTSL) should be offered by skilled attendants to all women. • In the context of AMTSL, skilled attendants should offer oxytocin in preference to oral misoprostol. • In the absence of AMTSL, WHO strongly recommends that a uterotonic drug (oxytocin or misoprostol) should be offered by a health worker trained in its use for prevention of PPH.

8. Misoprostol Prophylaxis: Ongoing Efforts • Ongoing research trials • To bolster evidence on its use/integration among various levels of health systems and providers • To confirm its effectiveness as part of AMTSL package • To determine if lower dose, 400 mcg, is safe & effective • To test its adjunct prophylactic use (oxytocin + miso) • Advocacy / Policy Efforts • Application submitted to WHO in Nov. ‘08 for inclusion of misoprostol prophylaxis in Essential Medicines List

9. Misoprostol for PPH Treatment Published studies • 8 non-controlled and 4 RCTs on misoprostol for PPH treatment • Range of doses and routes tested - - no definitive protocol/regimen exists • Studies test misoprostol use at different stages of PPH care, including : • (1) misoprostol alone for primary PPH txt • (2) misoprostol as an adjunct treatment to standard uterotonics • (3) as a last resort

10. Misoprostol Treatment: In Sum… • Fewer than 600 women have received misoprostol for PPH treatment in published literature • Data show that misoprostol causes rapid uterine contractions that reduce postpartum blood loss • Side effects dose dependent; mostly mild and transient; non-life threatening reported cases of high fever infrequent Insufficient data to support a specific misoprostol regimen for treatment of primary PPH, either following or in absence of prophylactic uterotonics or as adjunct to standard treatment (Blum, IJGO 2007)

11. Misoprostol Treatment: Current Research Questions Can misoprostol alone effectively stop postpartum bleeding when used to treat PPH? “Future randomised controlled trials are required to identify the best drug combinations, route, and dose of uterotonics, especially misoprostol, for the treatment of primary PPH. Another area of interest would be interventions for control of primary PPH following home deliveries, particularly in developing countries.” (Mousa et al. Cochrane Systematic Review 2007)

12. Misoprostol Treatment: Recently Completed Research Purpose Determine if misoprostol alone is a safe and effective treatment option for primary PPH (due to uterine atony) Study design Two hospital-based, double-blinded, placebo controlled, randomized controlled trials Study arms After PPH diagnosis, women randomized to either 800 μg sublingual misoprostol or 40 IU oxytocin IV Context Burkina Faso, Egypt, Ecuador, Turkey, and Vietnam: Study 1: oxytocin prophylaxis given during 3rd stage of labor Study 2: no oxytocin given during 2nd or 3rd stages of labor

13. % PPH Cases Treated (over 41,000 screened) Turkey 2.2% Vietnam 2.3 - 3.0% 6.8 – 12.2 % Ecuador 29.2% Egypt 2.9% 7.2% Burkina Faso 1.7%

14. Today’s News • Misoprostol works well in treating PPH due to uterine atony • Misoprostol has a role to play in treating PPH when oxytocin is available or not • Publications forthcoming • New evidence will be reviewed at Nov.’s WHO meeting to develop PPH Txt Guidelines

15. Implications of Results

16. Take Home Messages • Misoprostol is a safe and effective technology for PPH prevention and treatment • Some questions remain; however, if gold standard –injectable oxytocin -- is not feasible, misoprostol is recommended • Given low cost and ease of use, miso has potential to save women’s lives, particularly in resource-poor settings • Integration of this technology into existing programs and models is essential to sustainability and cost effectiveness

17. Thank You For more information -- Please visit our newly updated website!www.gynuity.org