A systematic review and meta-analysis led by ISGlobal adds evidence to the safety of high doses of ivermectin. This information is particularly relevant for projects that seek to use higher doses of the drug for the control of scabies, soil-transmitted helminths and malaria.
Ivermectin is a key anthelmintic drug that has been widely used in mass drug administration (MDA) campaigns for the control of onchocerciasis and lymphatic filariasis. The drug has a broad activity against other parasites, including intestinal worms, mites causing scabies, and even malaria-transmitting mosquitoes. Therefore, there is growing interest in using higher, fixed dose regimens of ivermectin in campaigns aimed at controlling these diseases.
Ivermectin is currently prescribed at doses between 150 and 400 µg/ kg. “For other applications, such as STH or malaria control, we would need to go beyond these doses,” explains Jose Muñoz, ISGlobal researcher and study co-author. Furthermore, administering fixed doses, rather than doses based on weight or height, would greatly facilitate the implementation of MDA activities. In fact, Muñoz leads STOP, a European-funded project that aims to test the safety and efficacy of a fixed dose combination of ivermectin plus albendazole to treat STH in children.
“The aim of this study was to systematically review the safety profile of high dose ivermectin and contribute to opening opportunities for expanded uses of this drug,” adds Alejandro Krolewiecki, senior author of the study and part of the STOP team. Six studies were included for the meta-analysis. They consisted of published trials for different clinical conditions, with a total of almost 1,000 participants, including healthy volunteers.
The analysis shows that the safety profile and adverse effects of ivermectin was not dose-dependent. In other words, the frequency and intensity of adverse effects was similar in groups receiving doses above or under 400 µg / kg. In one study, a small number of healthy volunteers received doses up to 2000 µg / kg (10 times the recommended dose). However, one trial did report transient ocular adverse events related with high doses of ivermectin in onchocerciasis patients, which can be of concern in this type of patients and is a call for caution.
“Although limited by the small number of studies, our review adds evidence to the safety of ivermectin at doses up to 800 µg/kg,” concludes Krolewiecki. Further studies are needed to evaluate the safety of ivermectin at higher doses, particularly in children under 15 kg and in pregnant women.
Navarro M, Camprubi D, Requena-Mendea A et al. Safety of high-dose ivermectin: a systematic review and meta-analysis. J Antimicrob Chemother. 2020. pii: dkz524. doi: 10.1093/jac/dkz524.