Data reporting ivermectin poisoning in humans are very scanty. It was previously demonstrated that ivermectin is well tolerated at doses up to ten times the highest Food and Drug Administration (FDA)-approved dose (200 µg/kg), with no evidence of associated toxicity, indicating that ivermectin accumulation is minimal [
9]. Another study involving 12 healthy volunteers who each received a single oral dose of 12 mg of ivermectin confirmed this hypothesis [
10]. In the present report, however, the hypothetical dose of ivermectin 3 mg ingested (~1200 mg) was approximately 100 times higher than the highest recommended dose. This high dose of ivermectin resulted in poisoning involving a central nervous system depression with dizziness, ataxia, headache, drowsiness, mydriasis, and a mildly altered state of consciousness (GCS, 13/15). A previous experimental study in rats revealed that gradually increased doses of ivermectin were associated with drowsiness at 10 mg/kg and depression of the central nervous system from 15 mg/kg [
11], though these symptoms were reversible after a few days. Our patient presented with bilateral mydriasis, kinetic ataxia, and hyperreflexia. These signs could be due to ivermectin stimulation of the orthosympathetic nervous system, resulting in bilateral mydriasis, and the parasympathetic nervous system, leading to an exacerbation of tendon reflex. Indeed, an experimental study in calves has previously demonstrated that some clinical signs such as ataxia are due to the cholinergic function of ivermectin mediated by gamma aminobutyric acid (GABA). Similarly, mydriasis and ataxia were also observed in some dogs receiving up to 600 mg/kg of ivermectin administered subcutaneously [
12]. In a double-blind placebo-controlled study, doses were higher and/or more frequent than those currently approved for human treatment, and the primary safety endpoint was mydriasis, accurately quantified by pupillometry [
9]. In another double-blind placebo-controlled trial, some patients treated with 800 µg/kg experienced a subjective dyschromatopsia or colored vision (yellow or red) [
13]. Our patient experienced reduced visual acuity, but this should be taken with caution since the patient reported vision problems before ivermectin poisoning. Also, the inability of ivermectin to cross the aqueous humoral barrier was previously described, likely due to its high molecular size, as other macrocyclic lactones. The blood-eye barriers thus block the penetration of ivermectin into the ocular globe [
14]. An MRI would have been necessary to better investigate the causes of this visual deficit. A blood test of ivermectin would also have been interesting to confirm the poisoning, as well as to monitor the elimination of the active principle.
This is the first report of a poisoning with ivermectin of ~100 times the recommended dose. This case report confirms the safety and tolerability of ivermectin, even at exceptionally high doses.