Safety of high-dose ivermectin: a systematic review and meta-analysis

Abstract

Background Ivermectin is a key anthelmintic for the control of neglected tropical diseases. The main indications for population-level control with ivermectin through mass drug administration are onchocerciasis and lymphatic filariasis; however, there is interest in using higher, fixed-dose regimens for the control of scabies, soil-transmitted helminths and malaria. Safety data for these higher-dose regimens are needed. Methods A systematic literature review and meta-analysis on the safety and doses of ivermectin was conducted. Eligible studies reported patient-level data and, for the meta-analysis, clinical trials reporting data on doses ≥200 and ≥400 μg/kg were included. Incidence ratios were used to compare adverse events by severity and organ system affected. Results The systematic search identified six studies for inclusion, revealing no differences in the number of individuals experiencing adverse events. A descriptive analysis of these clinical trials for a variety of indications showed no difference in the severity of the adverse events between standard (up to 400 μg/kg) and higher doses of ivermectin. Organ system involvement only showed an increase in ocular events in the higher-dose group in one trial for the treatment of onchocerciasis, all of them transient and mild to moderate in intensity. Conclusions Although within this review the safety of high-dose ivermectin appears to be comparable to standard doses, there are not enough data to support a recommendation for its use in higher-than-approved doses. Ocular adverse events, despite being transient, are of concern in onchocerciasis patients. These data can inform programme managers and guide operational research activities as new approaches for the use of ivermectin are evaluated.

WITHDRAWN: Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic

“…They likewise reported by 48 hours a >5000-fold decrease of viral RNA and maintenance of effect at 72 hours. Additional investigations were directed with sequential dilutions of ivermectin to build up the concentration-response pro le, and the authors described ivermectin as a powerful inhibitor effect of SARS-CoV-2, with an IC50 determined to be approximately 2 μM [17]. Physicians all over the world were utilizing Ivermectin off-label, As soon as the in vitro results were published.…”

Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?

“…A key consideration in any clinical intervention using ivermectin is its host-directed (IMPα-directed) mechanism of action. Host-directed agents that impact cellular activities that are essential to healthy function must be tested with caution; although ivermectin has an established safety profile in humans [23,25], and is US Food and Drug Administration-approved for a number of parasitic infections [1,3,5], it targets a host function that is unquestionably important in the antiviral response, and titration of a large proportion of the IMPα repertoire of a cell/tissue/organ likely to lead to toxicity. With this in mind, where a host-directed agent can be a "game-changer" in treating viral infection may well be in the initial stages of infection or even prophylactically (see Section 6) to keep the viral load low so that the body's immune system has an opportunity to mount a full antiviral response [11,17].…”

The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

“…Ivermectin has an established safety profile for human use (Gonzalez Canga et al, 2008;Jans et al, 2019;Buonfrate et al, 2019), and is FDA-approved for a number of parasitic infections (Gonzalez Canga et al, 2008;Buonfrate et al, 2019). Importantly, recent reviews and meta-analysis indicate that high dose ivermectin has comparable safety as the standard low-dose treatment, although there is not enough evidence to make conclusions about the safety profile in pregnancy (Navarro et al, 2020;Nicolas et al, 2020). The critical next step in further evaluation for possible benefit in COVID-19 patients will be to examine a multiple addition dosing regimen that mimics the current approved usage of ivermectin in humans.…”