Post-partum haemorrhage is a major cause of direct maternal death, causing around 33% of such deaths where maternal mortality is high,¹ 21% in countries with lower rates,² and 8% in England and Wales,³ An estimated 125,000 women, mainly living in developing countries, die every year from this cause, Parenteral ergometrine and methylergometrine are invaluable drugs in the treatment and prevention of excessive uterine bleeding following obstetric delivery.⁴

Occasional ineffectiveness of ergometrine has been reported by obstetricians and others working in developing countries. Most reference books note that parenteral ergometrine should be stored at a temperature not exceeding 8°C and be protected from light. These requirements are either not known by most people involved in drug supply in tropical countries or are not followed. In a field survey carried out in Bangladesh, Democratic Yemen and Zimbabwe none of the 24 samples of ergometrine injection taken from 20 different rural health facilities was kept in a refrigerator, and 5 had passed the manufacturer's expiry date by up to 12 months⁵. Only 9 (37%) conformed to USP and BP standards with levels of active ingredient between 90 and 110% of the stated amount; 8 (33%) had potencies of 80-89% and the remaining 7 (29%) had potencies of 20% or less. Several samples were presented in unstained glass.

In a longitudinal study in Sudan ergometrine lost 10% of its active ingredient during the first few months in Port Sudan and was found to be only 53% potent after 25 months within the country,⁶ In another longitudinal study, carried out by WHO and UNICEF on two series of essential drug kits shipped by container from Copenhagen to Lagos and Entebbe, ergometrine injection lost 6% of its active ingredient during 8 weeks in transport.^7,8 Under similar circumstances methylergometrine injection lost 2% of its potency. During transport the temperature within the container had been as high as 42.4°C

All studies, including some early field results of the present study which have been published elsewhere,^9,10,11,12 indicate that ergometrine injection is not stable in developing countries, where the drug is rarely kept under refrigeration, resulting in a decreased level of active ingredient in many samples taken from the field. A reduced potency of this vital and life-saving drug will have serious if not fatal consequences.

An additional problem is that there is no obvious alternative for the drug. In a literature review,¹³ quoting several other studies,^14,15,16,17 it has been suggested that methylergometrine maleate injection would be more stable than ergometrine maleate. However, this conclusion could not be confirmed in the WHO/UNICEF study as only one brand of each was included and as it was not clear whether the manufacturing process or the chemical composition were responsible for the observed difference in stability.¹⁸ A WHO technical working group in 1990¹⁹ and a literature review published in 1991²⁰ concluded that, in view of its fewer side effects, oxytocin rather than ergometrine is to be preferred for use in routine active management of the third stage of labour. However, there is insufficient information on the relative efficacy of these drugs, as on their stability in tropical climates.

Table 1 Storage guidelines and manufacturer's stability information on injectable oxytocics

Storage guidelines for injectable oxytocics are often contradictory and stability data from the manufacturers are far from consistent (see Table 1). One manufacturer indicated that the stability of ergometrine is very dependent on the manufacturing and filling process.