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Adesola Odunayo, DVM, MS, DACVECC, University of Tennessee

Pharmacology & Medications

|January 2016|Peer Reviewed

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Ivermectin is a macrocyclic lactone (ML) used to treat parasitic infections in dogs and cats.1


  • The lipophilic properties of MLs enable different routes of administration (ie, oral, cutaneous, injectable).2,3
    • As GABA agonists, MLs stimulate presynaptic release of GABA and increase its binding to postsynaptic receptors.
    • It is thought that MLs bind to glutamate-gated chloride channels in the central nervous system (CNS), resulting in hyperpolarization of the neurons.4  
  • Nematodes utilize GABA as their primary neurotransmitter, and prolonged stimulation of GABA release can lead to neuromuscular blockade, paralysis, and death.3  
  • In mammals, MLs have low neurotoxic properties, as they do not readily cross into the brain of mammals (except under certain circumstances—see Toxicity).
    • Ivermectin is largely excreted in feces as an unmetabolized parent compound.


  • Clinical signs of toxicity include ataxia, mydriasis, altered mentation, hypersalivation, vomiting, blindness, retinopathy, tremors, seizures, bradycardia, and/or respiratory depression.  
    • With acute intoxication, signs may occur within a few hours.
    • In animals being treated daily (eg, for demodicosis), clinical signs may occur after several days of ivermectin treatment.1  
  • Ivermectin is especially toxic when administered to dogs with a homozygous mutation in the multidrug resistance gene (ABCB1-1Δ, formerly MDR1) at a dose higher than 0.1 mg/kg.5,6
    • The absent P-glycoprotein allows the influx of ivermectin into the CNS.7
    • Collies are overrepresented, but Australian shepherd dogs, Shetland sheepdogs, and other herding breeds may harbor the mutation, making them susceptible to ivermectin and other drugs.8  
  • Dogs without the P-glycoprotein abnormality can tolerate ivermectin at doses as high as 2.5 mg/kg before clinical signs of toxicity are seen.9,10  
  • Young animals may be susceptible to ivermectin toxicosis because of an immature blood–brain barrier.  
  • Cats are thought to tolerate doses of 0.2-1.3 mg/kg, although toxicity has been reported in kittens at lower doses.1,11  
  • Toxicity can occur when ivermectin is administered topically, orally, or parenterally (ie, IM, IV, SC) or ingested through feces of treated horses, cows, or pigs.


  • History of administration or inadvertent ingestion of ivermectin is important in diagnosing toxicity.  
  • Ivermectin concentrations in the brain are the most important determinant of toxicity.1
    • Can also be detected in blood, liver, or adipose tissue, but there is little correlation between concentration in the blood and development of clinical signs  
  • Testing can be conducted for the ABCB1-1Δ gene mutation in animals that develop clinical signs after ivermectin administration.  
  • CBC, serum chemistry profile, and urinalysis results typically note nonspecific changes (eg, hemoconcentration, prerenal azotemia, hypoglycemia, elevations in liver enzymes) but may be helpful.12,13
    • Respiratory acidosis may be present secondary to hypoventilation.

Treatment & Prognosis

  • There are no specific antidotes for ivermectin toxicosis.
    • Animals with oral exposure should be properly decontaminated when possible.
      • If oral ingestion occurred within 1 to 4 hours of presentation, vomiting should be induced with apomorphine (0.03 mg/kg IV or subconjunctivally) or hydrogen peroxide (dogs only; 0.5 mL/kg PO).
    • Ivermectin undergoes enterohepatic recirculation in the GI tract, so multiple doses of activated charcoal (1-2 g/kg PO once with or without cathartic; subsequent doses without cathartic at 0.5-1 g/kg 3 times a day) may be beneficial.
    • Electrolyte concentrations, especially sodium, should be monitored when activated charcoal is administered.14
    • Animals with topical exposure should be washed with mild dishwashing detergent before additional treatment is initiated.  
  • Crystalloid fluid therapy should be provided for maintenance and any ongoing losses.  
  • In animals with hypoventilation (pCO2 >60 mm Hg), endotracheal intubation and mechanical ventilation should be initiated.
    • Referral to a 24-hour facility may be required for ongoing support of a patient that requires mechanical ventilation.  
  • Physostigmine, an anticholinesterase agent, may be administered at 1 mg/dog IV twice a day but generally causes only temporary improvement in neurologic status.15
    • Picrotoxin, a GABA antagonist, may improve neurologic status but also may contribute to seizure activity and should be used cautiously.12  
  • Recently, use of IV lipid emulsion has been described for treatment of animals with ML toxicity, including ivermectin.16-20
    • IV lipid emulsion is effective in humans with lipid-soluble drug toxicoses and appears to be beneficial in animals with ivermectin toxicosis.16-20
    • The recommended dose of a 20% solution is a 1.5-mL/kg bolus administered over 15 minutes, then 15 mL/kg administered over 60 minutes.21
      • The dose can be repeated if clinical signs of toxicosis recur.
      • IV lipid emulsion has reportedly reversed blindness and accelerated recovery in affected dogs.16  
  • Mildly to moderately affected animals have a fair-to-good prognosis for recovery with aggressive supportive care.

CBC = complete blood count, CNS = central nervous system, GABA = gamma-aminobutyric acid, GI = gastrointestinal, ML = macrocyclic lactone, pCO2 = partial pressure of carbon dioxide

References and Author Information

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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