Vermectin Special Precautions

Because ivermectin may interact with γ-aminobutyric acid (GABA) receptors in the CNS, the drug is not recommended in patients with an impaired blood-brain barrier (e.g., meningitis, African trypanosomiasis) or CNS disorders that may increase penetration of the drug into the CNS.
Pharmacogenomic Neurotoxicity Considerations: In humans, P-glycoprotein, encoded by the multi-drug resistance gene (MDR1), functions as a drug efflux transporter and appears to limit the uptake of ivermectin into the brain, thereby preventing potentially fatal neurotoxicity in most humans. However, neurotoxicity manifested as tremors, ataxia, sweating, lethargy, coma, and death has occurred in certain animals (e.g., collie dogs, inbred strains of mice) who exhibit an extreme sensitivity to ivermectin; this increased sensitivity to the drug's neurologic effects appears to be secondary to absent or dysfunctional MDR and P-glycoprotein. It is theoretically possible that some individuals could experience increased brain concentrations of ivermectin or increased sensitivity to the drug's effects leading to neurotoxicity because of altered expression or function of P-glycoprotein (e.g. through genetic polymorphism, concomitant use of inhibitors of the P-glycoprotein transport system) or other mechanisms, although extensive use of ivermectin in mass treatment programs indicates that such an increased susceptibility, if it exists, must occur rarely in humans. Although a number of single-nucleotide polymorphisms in MDR1 have been identified in humans and the presence of genetic defects similar to those seen in susceptible animals cannot be ruled out, no cases with complete loss of P-glycoprotein activity have been reported in humans to date.
Solution for injection: The significance of ivermectin related to neurotoxicity in humans is still uncertain but given the findings in animal studies and reported human cases, this effect should be considered before use of parenteral ivermectin in humans.
Precautions in Strongyloidiasis: Individuals receiving ivermectin for the treatment of strongyloidiasis should be advised of the need for repeated stool examinations to document clearance of Strongyloides stercoralis infection. In immunocompromised (e.g., HIV-infected) patients receiving ivermectin for the treatment of intestinal strongyloidiasis, an optimal dosage regimen has not been established through adequate and well-controlled clinical studies. Several courses of therapy (i.e., at intervals of 2 weeks) may be necessary and cure may not be achieved. Control of extra-intestinal strongyloidiasis in such patients is difficult, and suppressive treatment (i.e., once monthly) may be helpful.
Use in Children: The safety and efficacy of ivermectin in children weighing less than 15 kg have not been established. Some clinicians state that use of ivermectin is not recommended in young children (e.g., those weighing less than 15 kg or younger than 2 years of age) in part because the blood-brain barrier may be less developed than in older patients.
Use in the Elderly: Clinical studies of ivermectin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. While other clinical experience has not revealed age-related differences in response to ivermectin, the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly should be considered.