Mito
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- Dec 10, 2016
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Some have emailed Peat to get his opinion on Ivermectin safety.
Here are a few studies talking about safety.
In conclusion, there is evidence that serious neurological adverse events can occur with ivermectin beyond the treatment of O. volvulus complicated by concomitant high burden L. loa infection. Potential explanations include concomitantly administered drugs which inhibit CYP3A4 and polymorphisms in the mdr-1 gene. By comparison with the extensive post marketing experience with ivermectin in the successful treatment of parasitic infections, the total number of reported cases suggests that such events are likely rare. However, elucidation of individual-level risk factors could contribute to therapeutic decisions that can minimize harms. Further investigation into the potential for drug interactions and explorations of polymorphisms in the mdr-1 gene are recommended.
www.ncbi.nlm.nih.gov
Ivermectin is a widely used drug for the treatment and control of several neglected tropical diseases.1 The drug has an excellent safety profile, with more than 2.5 billion doses distributed in the last 30 years, and its potential to reduce malaria transmission by killing mosquitoes is under evaluation in several trials around the world.2 Ivermectin inhibits the in vitro replication of some positive, single-stranded RNA viruses, namely, dengue virus (DNV),3–5 Zika virus,4,6 yellow fever virus,7,8 and others.4,7,9
First, ivermectin, which targets glutamate-gated chlorine channels in invertebrates, may cross-target the GABA-gated chlorine channels present in the mammalian central nervous system (CNS) and cause neurotoxicity.19 This is normally prevented by an intact blood–brain barrier (BBB), but in patients with a hyperinflammatory state, endothelial permeability at the BBB may be increased and cause leaking of drugs into the CNS, potentially causing harm.20,21
www.ncbi.nlm.nih.gov
Ivermectin (IVM) is used for onchocerciasis mass drug administration and is important for control of lymphatic filariasis, strongyloidiases and Scarcoptes mange in humans. It is widely used for parasite control in livestock. Moxidectin (MOX) is being evaluated against Onchocerca volvulus in humans and is also widely used in veterinary medicine. Both anthelmintics are macrocyclic lactones (MLs) that act on ligand-gated chloride channels and share similar spectra of activity. Nevertheless, there are marked differences in their pharmacokinetics, pharmacodynamics and toxicity. Usually, both MLs are remarkably safe drugs. However, there are reports of severe adverse events to IVM, in some humans with high Loa loa burdens, and IVM can be neurotoxic in animals with defects in P-glycoproteins (P-gp) in the blood-brain barrier. We have compared the in vivo neurotoxicity of IVM and MOX in P-gp-deficient mice and their accumulation in brain. We also investigated their effects on mammalian GABA receptors. We show that MOX has a wider margin of safety than IVM, even when the blood-brain barrier function is impaired, and that the neurotoxicity in vivo is related to different effects of the drugs on GABA-gated channels. These observations contribute to understanding ML toxicity and open new perspectives for possible MOX use in humans.
journals.plos.org
Here are a few studies talking about safety.
In conclusion, there is evidence that serious neurological adverse events can occur with ivermectin beyond the treatment of O. volvulus complicated by concomitant high burden L. loa infection. Potential explanations include concomitantly administered drugs which inhibit CYP3A4 and polymorphisms in the mdr-1 gene. By comparison with the extensive post marketing experience with ivermectin in the successful treatment of parasitic infections, the total number of reported cases suggests that such events are likely rare. However, elucidation of individual-level risk factors could contribute to therapeutic decisions that can minimize harms. Further investigation into the potential for drug interactions and explorations of polymorphisms in the mdr-1 gene are recommended.
Serious Neurological Adverse Events after Ivermectin—Do They Occur beyond the Indication of Onchocerciasis?
Serious neurological adverse events have been reported from large scale community-based ivermectin treatment campaigns against Onchocerciasis volvulus in Africa. The mechanism of these events has been debated in the literature, largely focusing on the ...
www.ncbi.nlm.nih.gov
Ivermectin is a widely used drug for the treatment and control of several neglected tropical diseases.1 The drug has an excellent safety profile, with more than 2.5 billion doses distributed in the last 30 years, and its potential to reduce malaria transmission by killing mosquitoes is under evaluation in several trials around the world.2 Ivermectin inhibits the in vitro replication of some positive, single-stranded RNA viruses, namely, dengue virus (DNV),3–5 Zika virus,4,6 yellow fever virus,7,8 and others.4,7,9
First, ivermectin, which targets glutamate-gated chlorine channels in invertebrates, may cross-target the GABA-gated chlorine channels present in the mammalian central nervous system (CNS) and cause neurotoxicity.19 This is normally prevented by an intact blood–brain barrier (BBB), but in patients with a hyperinflammatory state, endothelial permeability at the BBB may be increased and cause leaking of drugs into the CNS, potentially causing harm.20,21
Ivermectin and COVID-19: Keeping Rigor in Times of Urgency
www.ncbi.nlm.nih.gov
Ivermectin (IVM) is used for onchocerciasis mass drug administration and is important for control of lymphatic filariasis, strongyloidiases and Scarcoptes mange in humans. It is widely used for parasite control in livestock. Moxidectin (MOX) is being evaluated against Onchocerca volvulus in humans and is also widely used in veterinary medicine. Both anthelmintics are macrocyclic lactones (MLs) that act on ligand-gated chloride channels and share similar spectra of activity. Nevertheless, there are marked differences in their pharmacokinetics, pharmacodynamics and toxicity. Usually, both MLs are remarkably safe drugs. However, there are reports of severe adverse events to IVM, in some humans with high Loa loa burdens, and IVM can be neurotoxic in animals with defects in P-glycoproteins (P-gp) in the blood-brain barrier. We have compared the in vivo neurotoxicity of IVM and MOX in P-gp-deficient mice and their accumulation in brain. We also investigated their effects on mammalian GABA receptors. We show that MOX has a wider margin of safety than IVM, even when the blood-brain barrier function is impaired, and that the neurotoxicity in vivo is related to different effects of the drugs on GABA-gated channels. These observations contribute to understanding ML toxicity and open new perspectives for possible MOX use in humans.
Relative Neurotoxicity of Ivermectin and Moxidectin in Mdr1ab (−/−) Mice and Effects on Mammalian GABA(A) Channel Activity
Author Summary Ivermectin (IVM) is used for onchocerciasis mass drug administration and is important for control of lymphatic filariasis, strongyloidiases and Scarcoptes mange in humans. It is widely used for parasite control in livestock. Moxidectin (MOX) is being evaluated against Onchocerca...
