Currently, the World Health Organization (WHO) recommends oxytocin--a chemical cousin of carbetocin--to prevent excessive bleeding during childbirth, but oxytocin must be stored and transported at 2–8o C, which is hard to do in many countries, including India, depriving many women of access to this drug, said the WHO study, published in the New England Journal of Medicine on June 27, 2018.
The new avatar of carbetocin does not require refrigeration and retains its efficacy for at least three years stored at 30o C and 75% relative humidity, as opposed to oxytocin--widely used but manufacture and sale were recently banned for private manufacturers--which needs refrigeration. This is critical because, of 37,387 Indian health sub-centres--basic government-run clinics--24% do not have electricity, with Jharkhand being the worst at 70%, followed by Bihar (64%) and Jammu & Kashmir (63%).
WHO researchers studied 29,245 women who gave birth vaginally at 23 hospitals in 10 countries--Argentina, Egypt, India, Kenya, Nigeria, Singapore, South Africa, Thailand, Uganda, and the United Kingdom--and found that heat-stable carbetocin is as safe and effective as oxytocin in preventing postpartum haemorrhage.
The ability of a drug to stanch bleeding is important, as India tries to improve on its 22% decline in maternal mortality ratio (MMR), from 167 in 2011-13 to 130 in 2014-16, according to government data. The MMR has missed development targets, as FactChecker reported on June 19, 2018, and lags countries such as Bhutan, Indonesia, Cambodia, and Botswana, according to 2015 World Bank data. Sri Lanka’s MMR is 30, a quarter that of India.
Despite improvements in maternal mortality, hemorrhage continues to be the largest direct cause of maternal death, accounting for 661,000 deaths worldwide between 2003 and 2009; India accounts for 17% of global burden of maternal deaths and the leading causes of death in India are haemorrhage (38%), sepsis (11%) and abortion (8%), as FactChecker reported on June 19, 2018.
Oxytocin is a key weapon in the struggle to reduce MMR, but there are problems with the way the drug is stored and used.
Oxytocin isn’t working the way it should
“Apart from fact that efficacy of oxytocin depends on certain conditions, across India, there is even a lack of awareness that oxytocin needs to be stored as a specific temperature and refrigeration,” Shivaprasad S. Goudar, professor at the Jawaharlal Nehru Medical College, Belgaum, and co-author of the study, told IndiaSpend. “And, therefore, the quality of oxytocin administered to pregnant women is sub-optimal.”
“The study’s results hold a lot of promise,” said Subhasri (she uses one name), chairperson, CommonHealth, a coalition working on maternal-newborn health and safe abortion.
However, there are three challenges, said Subhasri, to taking carbetocin national: One, the study doesn’t show that carbetocin is as effective as oxytocin for severe bleeding (more than 1,000 ml), and more trials may be necessary to prove carbetocin’s effectiveness to stanch severe bleeding; two, oxytocin is a drug out of patent, whereas carbetocin is under patent and is likely to be costlier; and three, as with oxytocin, there is a “huge potential” of carbetocin misuse.
Goudar said carbetocin will be “near to” oxytocin in cost because the WHO has an agreement with the manufacturer. “In India’s context, in the next few years, it (carbetocin) could emerge as a viable alternative,” he said, “as it will reduce the costs of storage and infrastructure which is required for ensuring oxytocin’s safe usage.”
As we said, the Centre stopped the manufacture and sale of oxytocin formulations by private companies. Only the Karnataka Antibiotics & Pharmaceuticals Ltd (KAPL), a public-sector company, was to manufacture oxytocin for domestic use from July 1, 2018. However, the ban was postponed on July 2, 2018, after protests by health practitioners, researchers and health activists.
“There is a huge potential for misuse of carbetocin, just like oxytocin, which has been banned by the government because of its rampant misuse,” said Subhasri. Oxytocin misuse is widespread in the dairy industry, where livestock are injected with oxytocin to make them release milk at a time convenient to farmers. The hormone is also used to increase the size of vegetables such as pumpkins, watermelons, brinjals, gourds and cucumbers, as the Hindustan Times reported on July 14, 2017.
Misuse apart, it will be a challenge to infuse carbetocin into the public-health system, experts said.
The challenges of spreading carbetocin nationwide
“The biggest challenge is the piloting the usage of carbetocin and its roll out in all states in India,” Nitin Bajpai, an independent health researcher, told IndiaSpend. “For instance, the population of Uttar Pradesh is very different from the population of Tamil Nadu. Thus, doing a pilot with carbetocin in one state and then generalising the results pan-India will be problematic.”
Administering carbetocin and monitoring the results are specific challenges.
“In simple terms, a vaccine or an injection may be effective, but if it is not administered properly, the data not collected properly and the results of pilot tests not leveraged effectively, then it won’t have the desired impact,” said Bajpai. “Most large-scale studies generally do not document these operational issues… which should be taken care of while taking a drug from a clinical trial stage to a mass roll-out.”
He also said that auxiliary nurses/midwives (ANMs), the frontline of the public-health system, aren’t trained to handle excessive bleeding in childbirth. “If they can handle vaginal deliveries, why can’t they be trained to handle postpartum haemorrhage?” asked Bajpai. “If doctors and nurses aren’t available, trained ANMs can help save lives in emergency situations.”
While carbetocin may hold greater potential to hasten the fall in maternal mortality, there are other related factors, such as anaemia, which directly causes a fifth of maternal deaths and was the associate cause of half these deaths, according to a 2014 study published in Nutrition, an international journal, IndiaSpend reported on August 29, 2017.
(Saha is a media & policy communications consultant with the Policy & Development Advisory Group, Delhi. In September 2018, he will be starting his PhD in International Development from the Institute of Development Studies, University of Sussex, UK.)
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