Ivermectin

Avermectin antiparasitic Macrocyclic lactone

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO Heartworm prevention: 6 mcg/kg monthly; Intestinal parasites: 0.2-0.4 mg/kg once; Sarcoptic mange: 0.2-0.4 mg/kg every 2 weeks for 2-3 treatments Monthly for heartworm prevention; single dose for intestinal parasites; repeated for mange Duration: Varies with indication
Notes: Do not use in Collies or other herding breeds with MDR1 mutation at high doses; use with caution.
Cat PO Heartworm prevention: 24 mcg/kg monthly; Intestinal parasites: 0.2-0.4 mg/kg once; Ear mites: 0.3 mg/kg topically or orally Monthly for heartworm prevention; single dose for intestinal parasites Duration: Varies
Notes: Cats are more sensitive to ivermectin; use with caution.
Horse PO 0.2 mg/kg once Single dose Duration: One dose, repeated as needed based on fecal egg count
Notes: Do not use in foals under 4 months of age; use with caution in sick or debilitated animals.
Cattle SC 0.2 mg/kg once Single dose Duration: One dose, repeated as needed
Notes: Subcutaneous injection in the neck; observe withdrawal times.
Sheep/Goat PO 0.2-0.3 mg/kg once Single dose Duration: One dose, repeated as needed
Notes: Use with caution; some strains of Haemonchus may be resistant.
Rabbit PO or SC 0.2-0.4 mg/kg once for ear mites; repeat in 10-14 days Single dose or repeated Duration: Varies
Notes: Use with caution; safety in rabbits is not well established.
Bird (exotic) PO or topical 0.2 mg/kg once for nematodes; topical for mites Single dose Duration: Varies
Notes: Limited data; use only under veterinary supervision.

Clinical Indications & Species Uses

General Indications
  • Broad-spectrum antiparasitic for nematodes and arthropods in various species.
Dog (Canine)
  • Heartworm prevention (Dirofilaria immitis)
  • Intestinal nematodes (e.g., hookworms, roundworms, whipworms)
  • Ectoparasites (e.g., sarcoptic mange, ear mites, demodectic mange in some cases)
Cat (Feline)
  • Heartworm prevention
  • Intestinal nematodes (e.g., hookworms, roundworms)
  • Ear mites (Otodectes cynotis)
  • Not typically used for external parasites due to safety concerns
Horse (Equine)
  • Strongyles (large and small)
  • Ascarids (Parascaris equorum)
  • Pinworms (Oxyuris equi)
  • Bots (Gasterophilus spp.)
  • Onchocerciasis
  • Habronemiasis
Cattle (Bovine)
  • Gastrointestinal roundworms (e.g., Ostertagia, Haemonchus, Cooperia)
  • Lungworms (Dictyocaulus viviparus)
  • Cattle grubs (Hypoderma spp.)
  • Mange mites (Sarcoptes, Psoroptes)
  • Lice (sucking and biting)
Small Ruminants (Sheep / Goat)
  • Gastrointestinal nematodes (e.g., Haemonchus, Teladorsagia)
  • Lungworms
  • Nasal bots (Oestrus ovis)
  • Mange mites
  • Lice
Rabbit & Small Mammals
  • Ear mites (Psoroptes cuniculi)
  • Intestinal nematodes (e.g., Passalurus ambiguus)
Exotic & Other Species
  • Reptiles: nematodes, mites; Small mammals (e.g., ferrets, guinea pigs): ear mites, intestinal parasites; Use with caution due to species-specific sensitivities.

Pharmacology & Mechanism of Action

Drug Class: Avermectin antiparasitic | Pharmacological Group: Macrocyclic lactone

Mechanism of Action: Ivermectin binds selectively and with high affinity to glutamate-gated chloride channels that occur in invertebrate nerve and muscle cells. This binding leads to an increase in the permeability of the cell membrane to chloride ions, causing hyperpolarization of the cell, resulting in paralysis and death of the parasite. It also interacts with other ligand-gated chloride channels, such as those gated by gamma-aminobutyric acid (GABA). In mammals, these channels are found only in the central nervous system, and ivermectin does not readily cross the blood-brain barrier, contributing to its safety margin in most species.

Pharmacodynamics: Ivermectin is a broad-spectrum antiparasitic agent effective against various nematodes, arthropods, and some ectoparasites. It is active against both immature and adult stages of many parasites. The drug is highly lipophilic, which allows it to accumulate in the fat and liver, providing a depot effect and prolonged activity. Its efficacy is dose-dependent, and it has a wide therapeutic index in most species, but certain breeds (e.g., Collies) may be sensitive due to a mutation in the MDR1 gene.

⚡ Pharmacokinetics Summary

Absorption: Ivermectin is well absorbed after oral administration in most species, with peak plasma concentrations occurring within 2-5 hours in dogs and cats. In ruminants, oral absorption is slower due to rumen degradation; subcutaneous administration provides more consistent absorption. The drug is also absorbed after topical application, but systemic levels are lower.
Distribution: Ivermectin is widely distributed throughout the body, with high concentrations in the liver, fat, and skin. It is highly lipophilic and accumulates in adipose tissue. It crosses the blood-brain barrier poorly in most species, but in animals with a defective P-glycoprotein (MDR1) gene, it can accumulate in the CNS, leading to neurotoxicity. It is excreted in milk, and in lactating animals, it can be transferred to nursing offspring.
Metabolism: Ivermectin is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, to various hydroxylated and demethylated metabolites. The metabolites are less active than the parent compound. In ruminants, metabolism occurs in the liver and also in the rumen microflora.
Excretion: Ivermectin is excreted primarily in the feces, with less than 2% excreted in urine. In lactating animals, a significant amount is excreted in milk. The elimination half-life varies by species: approximately 1.5-2 days in dogs, 2-3 days in cats, 2-3 days in horses, and 2-7 days in cattle, depending on the formulation.
Half-Life: Dog: 1.5-2 days; Cat: 2-3 days; Horse: 2-3 days; Cattle: 2-7 days (oral), 3-8 days (subcutaneous)
Bioavailability: Oral: ~50-60% in dogs and cats; Subcutaneous: ~100% in cattle; Topical: ~30-50% in cattle and horses.
Protein Binding: Ivermectin is highly protein-bound (93-99%) in plasma, primarily to albumin.

Available Formulations & Strengths

Oral Tablet 68 mcg, 136 mcg, 272 mcg (for heartworm prevention) (PO)
Oral Liquid 10 mg/mL (for cattle, sheep) (PO)
Injectable Solution 10 mg/mL (for cattle, swine), 1% solution (SC)
Pour-on Solution 5 mg/mL (for cattle) (Topical)
Paste 1.87% (for horses) (PO)
Topical Spot-on Various (for dogs and cats, often combined with other drugs) (Topical)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to ivermectin or other avermectins
  • Do not use in dogs with known MDR1 (ABCB1) gene mutation (e.g., Collies, Shelties, Australian Shepherds) at high doses
  • Do not use in cats that are very young (under 6 weeks) or debilitated
  • Do not use in horses intended for human consumption (in some countries)
  • Do not use in cattle producing milk for human consumption (unless specifically approved)
  • Do not use in animals with compromised blood-brain barrier (e.g., meningitis, severe systemic illness)
Warnings & Clinical Precautions:
  • Use with caution in animals with liver disease, as metabolism may be impaired
  • In dogs, use with caution in breeds sensitive to ivermectin; consider genetic testing for MDR1 mutation
  • In cats, use with caution as they are more sensitive to neurotoxic effects
  • In horses, do not use in foals under 4 months of age
  • In cattle, do not administer intravenously or intramuscularly; subcutaneous only
  • Avoid use in sick or stressed animals
  • Do not use in animals with known hypersensitivity
  • In food animals, observe withdrawal times
  • Use with caution in animals with heavy parasite burdens, as rapid kill may cause inflammatory reactions
  • In reptiles and exotic species, use only under veterinary supervision

Adverse Effects & Reactions

Common:

  • Transient injection site reactions (swelling, pain)
  • Salivation (especially in horses)
  • Mydriasis (in cats)
  • Depression or lethargy (at high doses)

Serious / Severe:

  • Neurotoxicity (ataxia, tremors, seizures, coma, death) especially in MDR1 mutant dogs or at high doses
  • Anaphylactic reactions (rare)
  • Hepatotoxicity (rare)
  • Bone marrow suppression (rare)

Rare:

  • Blindness
  • Pulmonary edema
  • Teratogenic effects (in laboratory animals)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
P-glycoprotein inhibitors (e.g., ketoconazole, itraconazole, cyclosporine, amiodarone) May increase ivermectin concentrations in the CNS, leading to neurotoxicity High
Other macrocyclic lactones (e.g., milbemycin, moxidectin) Additive toxicity Moderate
GABAergic drugs (e.g., barbiturates, benzodiazepines) Potential additive CNS depression Moderate
CYP3A4 inhibitors (e.g., erythromycin, clarithromycin) May increase ivermectin levels Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Mydriasis
  • Ataxia
  • Tremors
  • Depression
  • Coma
  • Respiratory depression
  • Death

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. In cases of recent oral ingestion, induce emesis (if safe) and administer activated charcoal. Provide intravenous fluids, respiratory support, and control seizures with diazepam or barbiturates. In severe cases, consider using physostigmine (controversial) or other supportive measures. Monitor vital signs and neurological status.

Food Animal Withdrawal Times

🥩 Meat: 28 days🥛 Milk: 0 days

Withdrawal times vary by country and formulation. For cattle, meat withdrawal is typically 28 days for injectable and pour-on; milk withdrawal is 0 days for pour-on but 9 days for injectable in some countries. For sheep, meat withdrawal is 14 days. Always follow local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F)

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light. Keep container tightly closed. Do not freeze.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs, cats, cattle, swine, sheep, and horses in various formulations. Some products are OTC for heartworm prevention in dogs, but prescription is required for others.

Extra-Label (Off-Label) Use: In the US, extra-label use of ivermectin in food animals is prohibited if it results in violative residues. In companion animals, extra-label use is permitted under AMDUCA with veterinary supervision. In horses, use is regulated; not for use in horses intended for human consumption.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Ivermectin is a cornerstone antiparasitic drug in veterinary medicine, but its use requires careful consideration of species, breed, and individual patient factors. In dogs, the MDR1 gene mutation can lead to severe neurotoxicity even at standard doses; therefore, genetic testing is recommended for at-risk breeds. In cats, ivermectin should be used with caution due to a narrower safety margin. In food animals, adherence to withdrawal times is critical to prevent drug residues in meat and milk. Resistance to ivermectin has been reported in some nematode populations, particularly in sheep and goats, so rotational deworming strategies and fecal egg count monitoring are advised. Always use the lowest effective dose and combine with good management practices to minimize resistance development.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)