TY - JOUR
T1 - Safety of high-dose ivermectin
T2 - A systematic review and meta-analysis
AU - Navarro, Miriam
AU - Camprubí, Daniel
AU - Requena-Méndez, Ana
AU - Buonfrate, Dora
AU - Giorli, Giovanni
AU - Kamgno, Joseph
AU - Gardon, Jacques
AU - Boussinesq, Michel
AU - Munoz, Jose
AU - Krolewiecki, Alejandro
N1 - Funding Information:
This study was carried out as part of our routine work. D.B. was funded by the Italian Ministry of Health ‘Fondi Ricerca Corrente – Linea 2, pro-getto 4’ to Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Sacro Cuore Don Calabria Hospital.
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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 ≥400μg/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 ng/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.
AB - 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 ≥400μg/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 ng/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.
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U2 - 10.1093/jac/dkz524
DO - 10.1093/jac/dkz524
M3 - Article
C2 - 31960060
AN - SCOPUS:85081945646
VL - 75
SP - 827
EP - 834
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 4
ER -