DAKAR, 16 March 2011 (IRIN) - A drug many health experts say can drastically cut postpartum haemorrhage - the leading cause of maternal deaths in the developing world - will be in the spotlight this month during the World Health Organization's (WHO) biennial review of its model list of essential medicines.
Health groups are urging WHO to include misoprostol for the prevention and management of postpartum haemorrhage (PPH), or excessive bleeding following childbirth. WHO in 2009 denied misoprostol for prevention of PPH but proponents hope new evidence presented for the 21-25 March WHO meeting in the Ghanaian capital Accra will bring a change.
An advantage of misoprostol for treating PPH in developing countries is that it is stable at room temperature and can be administered in tablet form, experts say. The primary drugs for PPH - oxytocin and ergometrine - need refrigeration and are injected. While oxytocin is cheaper, misoprostol is more cost-effective in many settings because of these other features, say health experts in their application to WHO.
Such drugs - called oxytocics - cause the uterus to contract, speed up delivery of the placenta and lessen blood loss.
"It is simply pragmatic - I am 100 percent in support of including misoprostol among our means for preventing or treating PPH until we get a better option," Lawal Oyeneyin, chief medical director at Mother and Child Hospital, Akure, Ondo State, Nigeria, told IRIN. He is among several who submitted letters of support.
PPH causes about a quarter of maternal deaths worldwide, according to WHO; Oyeneyin said it is "without a doubt" the most common cause of maternal death in Ondo State. "Why exclude misoprostol when the benefits outweigh the risks?"
Médecins Sans Frontières also wrote in support of the drug. "Oral misoprostol is a useful alternative for injectable oxytocics when they are not available or ineffective," said MSF international medical coordinator Myriam Henkens.
The essential medicines list (EML) is a guide for national and institutional essential medicines, according to WHO. While governments are not bound to follow it, the model list heavily influences national health ministries, experts say.
In rejecting the drug last time, WHO said some adverse effects were not well understood; the agency says further study is needed into safety and efficacy. It recommends the use of misoprostol in settings where it is not possible to use oxytocin or another injectable uterotonic, but it was not put on the list because trials had not proven efficacy; shivering and fever can occur, and "there is an unresolved concern of a possible increase in the risk of maternal mortality".
Five years ago Nigeria became the first country to include misoprostol for PPH among its essential medicines. Some governments find it difficult to do so because it is not on WHO's list, Oyeneyin said.
Listing misoprostol for PPH prevention "will break down this barrier", proponents say in letters to WHO.
Anthony Smith, emeritus professor of clinical pharmacology at Calvary Mater Hospital in New South Wales, has done several consultancies with WHO, particularly in the Pacific Islands.
"While oxytocin and ergometrine appear to be modestly superior to misoprostol in clinical trials, misoprostol is efficacious in its own right and is stable under hot conditions. Until such time as dependable storage exists for oxytocin and ergometrine, misoprostol will provide acceptable treatment for the prevention and treatment of PPH in these remote, hot locations," he said.
Misoprostol is a generic product and has several manufacturers. It was developed in the 1980s and approved in the US for prevention of gastric ulcers but has been used since in obstetrics and gynaecology. It is used in combination with mifepristone to terminate a pregnancy. Some health workers warn about misuse.
Getting misoprostol on the EML would be a step forward but just one step, according to proponents. They say the drug should be in the hands of community health workers and pregnant women, not uniquely at medical facilities. While having more women give birth in properly equipped clinics with skilled medical staff is the ideal for mother and infant health, experts say, this remains far from the reality for most women in rural sub-Saharan Africa and Asia.
"Where I work [in Kaduna and Zaria states] more than 90 percent of births take place at home; in Nigeria about two-thirds," said Clara Ejembi, from the department of community medicine at Ahmadu Bello University, Zaria State. In some cases home delivery is preferred - either because of custom or the quality of health facilities.
Nigeria is now revising guidelines on misoprostol to add advice on community use. Ghana, Senegal and Tanzania are also studying community access to misoprostol. The US Agency for International Development (USAID), which calls misoprostol "a highly promising technology that may be used by trained health workers working outside facilities and even in remote areas", is testing and introducing misoprostol in Afghanistan, Bangladesh, Nepal and Senegal.
However, WHO has expressed concern about advanced community distribution of misoprostol. Matthews Mathai of WHO's Making Pregnancy Safer programme told IRIN: "There is evidence that incorrect dosing can lead to excessive and violent contractions of the uterus leading to foetal distress, foetal death and uterine rupture."
Nigerian doctor Oyeneyin said the incorrect usage concern should not rule out access. "Opponents are worried about the safety profile of misoprostol. But the safety issue can be addressed through training.
"When you have a problem you should use all ammunition available to tackle it - in this case, that's oxytocin, ergometrine and misoprostol," he said. "It's ironic that the first two are on the model list of essential medicines while misoprostol is not. Of the three, misoprostol is most likely to be applicable in communities."
Godfrey Mbaruku, deputy director of Ifakara Health Institute in Dar es Salaam, Tanzania, said misoprostol must not be seen as a panacea, as PPH is not the only complication that can arise. "The idea is not to encourage women to deliver at home," he told IRIN. "But this allows them to have the drug on hand in case of PPH during a home delivery."
In northern Nigeria where home births prevail, research has shown that distributing misoprostol in the communities is a viable approach, Ejembi said. "Among community leaders acceptance is very high; people are ready to use this and advocate it. WHO people should come and let me take them around to the communities so they can hear the people's voices."
She said women in the communities where she works recognize the value of misoprostol. "If we were ever to remove this drug from communities there would be riots."