Quality of medicines for life-threatening pregnancy complications in low- and middle-income countries: A systematic review

Abstract

Background There are concerns about the quality of medicines available in low-and middle-income countries (LMIC) to manage hemorrhage, pre-eclampsia/eclampsia and sepsis. We aimed to identify, critically appraise, and synthesize the findings of studies on the quality of these three types of medicines available in LMIC. Methods This systematic review searched Medline, EMBASE and LILACS (from inception to 25 May 2020) for studies on the quality of selected medicines available in LMIC that provided at least the amount of active pharmaceutical ingredient. We contacted study authors for additional information. We excluded simulation studies. We used the MEDQUARG tool to assess study quality. The main outcome was the prevalence of failed samples. Findings We identified 9699 unique citations and included 34 studies (3159 samples from 40 countries) in the review. Most studies (65%) had low quality (scores <6/12). Overall, 48.9% of 1890 uterotonic samples (19 studies) failed quality tests; failures rates were 75% for ergometrine and nearly 40% each for oxytocin and misoprostol. The overall prevalence of failed injectable antibiotics (1090 samples, 18 studies) was 13.4%, ranging from 2.9% for injectable metronidazole (34 samples, 3 studies) to 16.0% for cefazolin (449 samples, 2 studies). The prevalence of low quality magnesium sulphate (179 samples, 2 studies) was 3.4%. We did not find any studies on the quality of carbetocin, tranexamic acid, or clindamycin.

Quality of oxytocin and misoprostol in health facilities of Rwanda

“…Especially in LMICs, the quality of medicines often fails to meet the pharmacopeial specifications, and this has far-reaching adverse consequences for patients, families, national health systems and the economy [ 11 , 12 ]. The use of substandard oxytocin or misoprostol preparations in the management of PPH may lead to therapeutic failure in the treatment of excessive bleeding, and even to the death of the patient [ 13 , 14 ]. Avoiding such preventable deaths is one of the key measures required to reach SDG 3.1.…”

“…A systematic review published by Torloni et al in 2016 [ 13 ] listed eight studies on the quality of oxytocin conducted in LMICs. In a subsequent systematic review published by the same authors in 2020 [ 14 ], the number of included oxytocin quality studies had increased to 14. Overall, 39.7% of the oxytocin samples investigated in all these studies had been reported to fail quality testing.…”

“…An insufficient content of the active pharmaceutical ingredient (API) represented by far the most frequently found deficiency. The overall percentage of failing samples had been 31.4% for studies conducted in the time period of 2000–2011 (n = 363 samples), but had increased to 44.4% for studies conducted from the year 2012 onwards (n = 611 samples) [ 14 ]. This indicates that in the last two decades, the quality problems of oxytocin have increased rather than decreased.…”

“…Another study conducted in Ethiopia reported a failure rate of only 4% within 45 oxytocin samples [ 25 ]. In all these studies, the failure rate resulted nearly exclusively from an incorrect API amount determined in the samples [ 14 ]. Therefore, the different failure rates reported are not due to different parameters being tested in the different studies.…”

“…In spite of these well-documented problems, misoprostol quality in LMICs has received much less attention than oxytocin quality. The above-mentioned review published by Torloni et al [ 14 ] lists, besides the study by Hall, only two further studies which investigated the quality of misoprostol tablets: Anyakora et al [ 22 ] reported that 56 (33.7%) out of 166 misoprostol samples collected in Nigeria failed quality testing due to incorrect API content, but the study did not state the exact amount of API detected in the samples. Hagen et al [ 24 ] reported that 5 (17%) out of 30 misoprostol samples from Malawi failed pharmacopeial specifications, notably all five with extreme deviations since they contained only 12.7–30.2% of the declared amount.…”