Serious adverse reactions associated with ivermectin: A systematic pharmacovigilance study in sub-Saharan Africa and in the rest of the World

Abstract

Background: Ivermectin is known to cause severe encephalopathies in subjects infected with loiasis, an endemic parasite in Sub-Saharan Africa (SSA). In addition, case reports have described ivermectin-related serious adverse drug reactions (sADRs) such as toxidermias, hepatic and renal disorders. The aim of this study was to identify suspected sADRs reported after ivermectin administration in VigiBase, the World Health Organization's global individual case safety reports database and analyze their frequency relative to the frequency of these events after other antinematodal drugs reported in SSA and other areas of the world (ROW).

Methods: All antinematodal-related sADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate nervous, cutaneous, psychiatric, respiratory, renal, hepatic and cardiac suspected sADRs reported after ivermectin and benzimidazole drug administration across the world, in SSA and RoW.

Principal findings: 2041 post-ivermectin or post-benzimidazole suspected sADRs were identified including 667 after ivermectin exposure (208 in SSA and 459 in the RoW). We found an increased reporting for toxidermias, encephalopathies, confusional disorders after ivermectin compared to benzimidazole drug administration. Encephalopathies were not only reported from SSA but also from the RoW (adjusted reporting odds ratios [aROR] 6.30, 95% confidence interval: 2.68-14.8), highlighting the fact these types of sADR occur outside loiasis endemic regions.

Conclusion: We described for the first time suspected sADRs associated with ivermectin exposure according to geographical origin. While our results do not put in question ivermectin's excellent safety profile, they show that as for all drugs, appropriate pharmacovigilance for adverse reactions is indicated.

Fig 1. Number of Individual Case Safety Reports (ICSRs) per country and distribution of sADRs of the 6 most reported SOCs (created with R software and the Rworldmap package).

The pie charts show the proportion of the most reported SOCs described by country. The number next to the pie chart represents the number of ICSRs by country (an ICSR can contain multiple SOCs).

Fig 2. Number of Individual Case Safety Reports (ICSRs) per African country and distribution of serious ADRs of the 6 most reported SOCs (created with R software and the Rworldmap package).

The pie charts show the proportion of the most reported SOCs described by country. The number next to the pie chart represents the number of ICSRs by country (an ICSR can contain multiple SOCs).

Fig 3. Number of Individual Case Safety Reports (ICSRs) per European country and distribution of sADRs of the 6 most reported SOCs (created with R software and the Rworldmap package).

The pie charts show the proportion of the most reported SOCs described by country. The number next to the pie chart represents the number of ICSRs by country (an ICSR can contain multiple SOCs).