Stability of Injectable Oxytocics in Tropical Climates: Results of Field Surveys and Simulation Studies on Ergometrine, Methylergometrine and Oxytocin - EDM Research Series No. 008
(1993; 50 pages) View the PDF document
Table of Contents
View the documentSummary
Close this folderIntroduction
View the documentOutline of the study
View the documentAcknowledgments
Open this folder and view contentsMaterials and methods
Open this folder and view contentsResults
Open this folder and view contentsDiscussion
View the documentConclusions and recommendations
View the documentReferences
Open this folder and view contentsAnnexes
 

Introduction

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

Ergometrine injection

 

Goodman and Gillman, 196021

Store at 0-12 °C, protect from light

USPDI, 198622

Store <40°C, pref. 15-30°C, protect from light and freezing

BP, 1988 23

Store at 2-8°C

Martindale, 198924

Store at 2-8°C, protect from light

Vitarine, 197525

If stored <17°C: 3 yr

Lily, 197525, 198326

If stored at 15-30 °C: 2 m

Sth Tees Hlth Authority, 198527

If stored at 10-15 °C and protected from light, as long as no discolouration has occurred

   

Antigen, 198728

If kept at room temperature: 13m

Gedeon Richter, 1988

If kept <15 °C and protected from light: 2 yr

Paris Chemical, 1988

If stored at 2-8°C 2 yr

Scanpharm, 1988

After lyr at 23°C; 23% loss of potency observed

Medisca, 1989

If stored <25°C and protected from light: 3 yr

 

Filling under N2 and protected from light, adding antioxidants, improves stability

   

Methylergometrine injection

 

Martindale, 198929

Store <8°C, fill under N2, protect from light

USPDI-630

Store <40°C, preferably between 15-30°C protect from light and freezing

Sandoz Netherlands

If stored <25°C: 3y

 

If stored <30°C, 18m no loss of potency

Medisca

If stored <25°C, protected from light: 3y

   

Oxytocin injection

 

Martindale, 198931

Store at 2-8°C; expiry 3y

 

If stored <25°C: 2y

BP, 198832

Store at 2-15°C, pH between 3.5-4.5

Sandoz Australia, 1989

If stored <25°C, protected from light: 3y

 

If stored at 30°C 50% loss of potency after 4y

 

5000k, 150W light: stable for 96h

Sandoz UK, 1989

If stored at 8-22°C, protected from light: 3y

Medisca, 1989

If stored <25°C, pH 3.1-4.9: no change

 

Short period of >25°C is possibly harmful

Scanpharm, 1988

Stored at 23°C: no change observed after 10m

   

Ergometrine/oxytocin injection

 

BP, 198833

Store <25°C; expiry at least 2y

Sandoz UK, 1989

If stored at 8-22°C, protected from light: 2y

 

If stored at 25°C in pack: 3m shelf life

 

Any light causes rapid degradation.

Sandoz Australia, 1989

If stored at 25°C: stable for 4-5 days

 

5000k, 150W light, at 25°C: after 4-5 days 50% potency loss

 

observed for ergometrine

 

If stored >25°C: great loss of stability

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.

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