Miriam Navarro1, Daniel Camprubí2, Ana Requena-Méndez2, Dora Buonfrate3, Giovanni Giorli3, Joseph Kamgno4, Jacques Gardon5, Michel Boussinesq5, Jose Muñoz2, Alejandro Krolewiecki2,6. 1. Department of Public Health, Science History and Gynecology, Universidad Miguel Hernández de Elche, Alicante, Spain. 2. Barcelona Institute for Global Health (ISGlobal) Hospital Clínic - Universitat de Barcelona, Barcelona, Spain. 3. Department of Infectious - Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy. 4. Centre de Recherche sur les Filarioses et autres Maladies tropicales, Yaounde, Cameroon. 5. Institut de Recherche pour le Développement, Montpellier, France. 6. Instituto de Investigaciones de Enfermedades Tropicales Universidad Nacional de Salta/CONICET, Orán, Argentina.
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.
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 onchocerciasispatients. These data can inform programme managers and guide operational research activities as new approaches for the use of ivermectin are evaluated.
Authors: Andrew Bryant; Theresa A Lawrie; Therese Dowswell; Edmund J Fordham; Scott Mitchell; Sarah R Hill; Tony C Tham Journal: Am J Ther Date: 2021-06-21 Impact factor: 2.688
Authors: Ali A Samaha; Hussein Mouawia; Mirna Fawaz; Hamad Hassan; Ali Salami; Ali Al Bazzal; Hamid Bou Saab; Mohamed Al-Wakeel; Ahmad Alsaabi; Mohamad Chouman; Mahmoud Al Moussawi; Hassan Ayoub; Ali Raad; Ola Hajjeh; Ali H Eid; Houssam Raad Journal: Viruses Date: 2021-05-26 Impact factor: 5.048
Authors: Alejandro Krolewiecki; Adrián Lifschitz; Matías Moragas; Marina Travacio; Ricardo Valentini; Daniel F Alonso; Rubén Solari; Marcelo A Tinelli; Rubén O Cimino; Luis Álvarez; Pedro E Fleitas; Laura Ceballos; Marcelo Golemba; Florencia Fernández; Diego Fernández de Oliveira; German Astudillo; Inés Baeck; Javier Farina; Georgina A Cardama; Andrea Mangano; Eduardo Spitzer; Silvia Gold; Carlos Lanusse Journal: EClinicalMedicine Date: 2021-06-18
Authors: Daniel Camprubí; Alex Almuedo-Riera; Helena Martí-Soler; Alex Soriano; Juan Carlos Hurtado; Carme Subirà; Berta Grau-Pujol; Alejandro Krolewiecki; Jose Muñoz Journal: PLoS One Date: 2020-11-11 Impact factor: 3.240