‘Drugs given to Nigerian women at childbirth have quality issues’

In 2015, it was estimated that 58,000 women in Nigeria died at childbirth, making the country retain an unenviable top spot in global maternal mortality. The situation is not one without solution, and one of these, as simple as it may seem, is proper storage of certain medicines meant to be administered when women are giving birth. BusinessDay’s Caleb Ojewale discussed some of these issues with Fiona Theunissen, program manager for maternal health with concept foundation, a nongovernmental organisation based in Geneva that works on access to quality assured reproductive and maternal health medicines.

Can you tell us what your work in Nigeria entails, and how long it has been?

We are working on some programs that affect Nigeria and we have been working on one specific program, which is around the quality of Uteritonics. It is a global project but we have focused on Nigeria, India, and Kenya. Nigeria and India specifically because they have very high numbers of maternal deaths and Uteritonics are one of the key interventions that can reduce maternal mortality.

What has your experience been so far and findings from working on this project in Nigeria?

Around the world, we have a lot of evidence on problems with the quality of reproductive and maternal health medicines, particularly the quality of Oxytocin and Misoprostol which are two drugs recommended by the World Health Organization for the prevention of postpartum haemorrhage. We know that these two drugs suffer from quality problems at the manufacture level and through degradations. Oxytocin is a medicine, which needs to be kept in the cold chain because when it is exposed to heat, it starts to decompose.

Misoprostol needs to be specially packaged and properly stored because if it exposed to moisture, it degrades. Therefore, when these products have less than the normal required amount of Active Pharmaceutical Ingredient in them, they do not do what they are supposed to do.

Some of the work that we have been involved with in Nigeria is research with professionals on their experience of quality. We have worked with obstetricians, gynaecologists, nurses, and midwives to learn about their experiences in health facilities and quality of these medicines.

We know from research that there is widespread poor quality because physicians and healthcare workers are not seeing the effects that they expect from the drugs (used when women are giving birth). The World Health Organization recommends that every woman who gives birth is given an injection of Oxytocin or a dose of Misoprostol to help contract the uterus and that way, close off the blood vessels to prevent postpartum haemorrhage.

“We know from research that there is widespread poor quality because physicians and healthcare workers are not seeing the effects that they expect from the drugs (used when women are giving birth).”

Now, if the woman is given a drug and it doesn’t contain what it should, then the uterus would not contract. Healthcare workers can detect when this happens and will see that women are continuing to bleed through those blood vessels that have been left open after the baby has been born. So, what they are doing is often using two, three, four doses of Uteritonics to get those uterine contractions to stop this bleeding.

We also are aware of the study conducted by the United States Pharmacopoeia’s Nigerian office with NAFDAC on sampling of the quality of Oxytocin in Nigeria. That study showed that 64 percent of the Oxytocin sampled was out of manufacturer’s specifications. So we know anecdotally that physicians and healthcare workers are experiencing poor quality (in the use of this drug).

We know factually from testing, that poor quality exists out in the field. We also know from other studies in the past like the UN Commission on Life-Saving Commodities, United States Pharmacopoeia studies in a number of countries, and a number of other quality surveys that quality is a really big issue in maternal health medicines. This also applies to magnesium sulphate which is used for eclampsia and pre-eclampsia which are the number two killer of women during childbirth. What we are trying to do is bring these issues to life, increase awareness of these problems, and then try identifying solutions.

In your findings so far, you mentioned that there isn’t enough cold chain storage, so that makes some of the medicines go bad. What are you doing to help resolve this?

One of the other findings that I am going to mention is that there is widespread belief that Oxytocin does not need to be kept in the cold chain. In Nigeria for example and a number of other countries, Oxytocin is procured from manufacturers that have labelled the product store at room temperature or store at twenty degrees, store under thirty degrees.

The WHO does not recognize this labelling as being correct for Oxytocin. We have collected together a number of studies on the stability of Oxytocin and together with the World Health Organization, USAID, the Reproductive Health Supplies Coalition and Pact, contributed to a publication, which is an advocacy framework on the right messaging for Oxytocin, that it should be kept in the cold chain. This is in order to ensure that by the time the woman receives it, it is going to be a quality medicine.

There is a misconception that you can leave this product on the shelf and if you do that, there is a very good chance that it is not going to work as efficiently as it should. One of the things we have been doing is trying to increase awareness of the fact that Oxytocin should be kept in the cold chain. So we have our messages framework which we are starting to roll out, and there will be a number of publications around this topic.

Some of the actions that countries can do are ensure that cold chain goes the whole way to the last woman. It is ensuring that at every health post where a woman can give birth, there is cold chain. But it has to go the whole way from the manufacturer right down to the day before the woman receives it to be able to ensure that medicine is quality. No one person in that supply chain can generally tell what has happened before or what will happen after they handle it and in a supply chain, you have a really large number of people who will handle the medicine. Unless you say it is going to be refrigerated the whole way, nobody sort of knows what has happened at any other point. It can experience some temperature excursions but you do not know how many times it has experienced those or for how long. So the safest approach is to call interest in the cold chain.

The next approach is to use a heat stable medicine and there is a misconception that some Oxytocin is heat stable; it is not. There has been a number of activities over the last 10 to 15 years to look for a heat stable Oxytocin or a heat stable Uteritonic. Misoprostol is a heat stable Uteritonic and it can be used. So, as long as you procure quality Misoprostol and it is packaged properly, that is an alternative for countries. There is another alternative that is coming to low income countries through a collaboration between the World Health Organization, Mark for Mothers and Ferring Pharmaceuticals to introduce heat stable Carbetocin. It is Uteritonic injected just after the woman has given birth and it has proven stability studies. So at thirty degrees, the heat stable Carbetocin maintains its potency for three years. We are waiting for four-year stability studies. It has a long shelf life at thirty degrees and at forty degrees for nine months. This is a significant progress over the stability of Oxytocin, a very significant one.

Which means for a country like Nigeria, Oxytocin is probably  not a good idea?

No

Considering electricity challenges in Nigeria, where some critical health procedures even get stalled because of it, how then will they provide refrigeration for medicines like this?

There are different medicines with different ways of acting on a woman and there needs to be a suite of options, so Uteritonics are used for up to four different things. You can use them for induction of labour which is starting labour, augmentation which is speeding up labour,  prevention of postpartum haemorrhage and treatment of postpartum haemorrhage. Oxytocin can be used for all of those four things so it is a very important drug, and countries need to work on improving their cold chain. It is really important that we work on cold chain.

The number one killer of women is postpartum haemorrhage, so prevention and treatment are critical so having a drug that is going to work for that part is important. Misoprostol can be used for all of these things as well; however, there are ongoing studies around; induction, augmentation and the right doses. Heat-stable Carbetocin can be used for prevention. WHO guidelines currently being drafted are likely to include heat stable Carbetocin but only for prevention, not treatment. It is important that all these things are available and at the right quality at the time the women receives them.

What is important is preventing postpartum haemorrhage because it kills women. Losing women’s lives has a number of different costs and this is a possibility through postpartum haemorrhage. This has a number of implications when it happens such as women requiring blood, which is not regularly available in Nigeria.