Quality of oxytocin and misoprostol in health facilities of Rwanda

Abstract

Sustainable Development Goal 3.1 calls for a reduction of the maternal mortality ratio to less than 70 per 100,000 live births by 2030. The most important cause of maternal mortality is post-partum haemorrhage (PPH). Oxytocin injections and misoprostol tablets are medicines of first choice for the management of PPH in low- and middle-income countries (LMICs). Unfortunately, both substances are chemically unstable, and previous studies have revealed serious quality problems of these medicines in LMICs. The present study is the first report on their quality in Rwanda. From 40 randomly selected health facilities (hospitals, health centers, retail pharmacies and private clinics) in different parts of Rwanda, as well as from six wholesalers and government stores, oxytocin injections and misoprostol tablets were collected. Oxytocin storage temperatures in the health facilities were monitored for six months using temperature data loggers, and found to correctly follow the storage requirements stated by the manufacturers (2–8°C, or room temperature) with few minor deviations. Oxytocin injections (57 samples, representing seven batches of four brands) were tested for their oxytocin content and pH value according to the United States Pharmacopeia. Twenty-four samples from three European manufacturers passed all tests. However, all nine samples of one batch of a Chinese manufacturer showed an excessive content of oxytocin (range 117.2–121.5% of the declared amount). Another batch of the same manufacturer showed extreme variations of the concentration of the preservative benzyl alcohol. Misoprostol tablets (25 samples, representing ten batches of six brands) were tested for content and dissolution according to the International Pharmacopoeia. Fifteen samples passed, but all 10 samples of two brands from India failed with extreme deviations, containing only 42.5–48.7% of the stated amount of misoprostol. In conclusion, oxytocin quality in Rwanda was better than reported from other African countries. However, two extremely substandard brands of misoprostol tablets were found. The Rwandan authorities reacted quickly and efficiently, and recalled these substandard medicines from the market. For oxytocin and misoprostol, with their well-known problems of quality and stability, procurement should possibly be restricted to medicines which are WHO-prequalified or which have been manufactured in countries with stringent regulatory authorities.

What do healthcare providers think of the quality of uterotonics? A mixed-methods systematic review

“…Despite the prevalent belief that misoprostol is a stable and reliable drug, several studies published over the last years raise concerns about the quality of this medicine 20 21 27 47 48. The recognition that misoprostol can have significant quality issues in LMICs was largely lacking until the publication of a systematic review by Torloni et al in 2020 20.…”

“…Despite their clinical importance in maternal health, the quality of oxytocin and misoprostol is substandard in many settings, especially in LMICs, mainly due to low content of active pharmaceutical ingredient 19–21. This may be due to production or packaging issues, or suboptimal storage conditions 22.…”

Substandard and falsified medical product recalls in Zambia from 2018 to 2021 and implications on the quality surveillance systems

“…39 , 65 – 67 This allows stakeholders such as researchers to produce objective evidence that can inform regulatory decisions and protect public health, as illustrated in Malawi and Rwanda, where two extremely substandard brands of misoprostol tablets were found during a quality survey and led to the issuance of recalls by the regulatory authorities in the two countries and the WHO issued an alert to other countries. 68 , 69 Therefore, it is recommended that all alerts be uploaded to a publicly available database (e.g. ZAMRA website and Med Safety mobile app).…”

Quality of oxytocin and tranexamic acid for the prevention and treatment of postpartum hemorrhage in Kenya, Nigeria, South Africa, and Tanzania

“…More recent studies revealed the low quality of oxytocin products in the Democratic Republic of the Congo (15 samples, 80% substandard), 9 Nigeria (159 samples, 74.2% failed), 10 and Nepal/Vietnam (42 samples, 31.0% failed) 11 . In contrast, there are also studies showing moderate and good quality oxytocin products 12–14 . For example, a study in Malawi and Ethiopia showed 89% and 96% of the samples, respectively, meeting the criteria 13,14 .…”

“…11 In contrast, there are also studies showing moderate and good quality oxytocin products. [12][13][14] For example, a study in Malawi and Ethiopia showed 89% and 96% of the samples, respectively, meeting the criteria. 13,14 A more recent systematic review by Torloni et al 15 found that, overall, around 40% of oxytocin samples were substandard.…”