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.

Safety and Tolerability of Ivermectin and Albendazole Mass Drug Administration in Lymphatic Filariasis Endemic Communities of Tanzania: A Cohort Event Monitoring Study

“…Previous clinical trials and observational studies reported similar common AEs, including headache, pruritus, muscle pain, coughing, dyspnea, nausea, vomiting, diarrhea, confusion, and skin reactions [ 7 ]. The same events were reported in higher numbers through spontaneous reporting to the WHO’s Vigibase, although the incidence rate could not be quantified [ 17 ]. Safety studies conducted elsewhere using diverse study designs, target populations, and treatment indications reported varying incidence rates of mild-to-moderate AEs in the first two days of treatment [ 25 , 26 , 27 , 28 ].…”

“…Although millions of people in Africa are receiving periodic MDA, safety data from large-scale active CEM studies are scarce partly due to the lack of fully functional pharmacovigilance systems in the region [ 10 , 11 , 12 ]. The WHO’s global individual case safety reports database (VigiBase) recently reported serious suspected ADRs and safety signals associated with ivermectin use and the under-reporting of ADRs in SSA [ 17 ]. Under or incomplete reporting of AEs, lack of information on baseline characteristics embracing the number of drug administrations, and the absence of denominators are major drawbacks inherent in spontaneous reporting pharmacovigilance databases such as VigiBase [ 18 ].…”

Neuropsychiatric manifestation of the drugs used in the treatment of SARS-2-CoV-2019 (COVID-19) infection and their management: An overview and practice implications

“…Precautions and Adverse neuropsychiatric Effects: The common neuropsychiatric adverse effects (A/Es) (data from the treatment of helminthic infections) are weakness, increased sleep, headache (10%), dizziness (7.5%)( Chandler, 2018 ). Additionally, encephalopathies/delirium, psychotic disorders( Mohapatra & Sahoo, 2015 ), suicidal behavior ( Kaur et al, 2017 ) have been reported with its use( Campillo et al, 2021 ).…”

Severe cutaneous adverse reactions associated with systemic ivermectin: A pharmacovigilance analysis

“…Disproportionality analysis revealed a significant association between systemic ivermectin and reporting of any SCARs, confirming a recent study of VigiBase, another pharmacovigilance database. 11 Interestingly, SCARs were reported more in African countries compared to other cutaneous AEs. This could be explained by under‐reporting of milder cutaneous AEs in these countries compared with North American or European countries, or by increased incidence of HIV carriers in Africa, 12 which is a risk factor for some SCARs, in particular SJS and TEN.…”