Ivermectin
Ivermectin is a prototype **avermectin** antiparasitic agent widely used across multiple veterinary species. It is a macrocyclic lactone derivative highly effective against a broad spectrum of nematodes and arthropods. **Key Clinical Highlights:** * **FDA-Approved Uses:** Heartworm prevention in dogs and cats; treatment of gastrointestinal roundworms, lungworms, grubs, lice, and mites in cattle, swine, horses, reindeer, and bison. * **Extra-Label Uses:** Microfilaricide, slow-kill adulticide (often combined with doxycycline), and treatment for generalized demodicosis and scabies in small animals. * **Genetic Sensitivity:** Extreme caution is required in breeds susceptible to the **ABCB1-1ฮ (formerly MDR1)** mutation (e.g., Collies, Australian Shepherds, Shetland Sheepdogs, Long-haired Whippets). These dogs lack a functional P-glycoprotein pump at the blood-brain barrier, leading to severe, potentially fatal CNS toxicity at doses commonly used for mange or microfilariae. * **Toxicity Profile:** Generally safe at low heartworm preventative doses (even in MDR1 dogs), but neurotoxicity risk increases significantly at higher doses or when combined with P-glycoprotein inhibitors.
Mechanism: Ivermectin exerts its antiparasitic effect by binding selectively and with high affinity to **glutamate-gated chloride channels** which occur in invertebrate nerve and muscle cells. * **Primary Mechanism:** Binds to glutamate-gated chloride channels โ increases cell membrane permeability to chloride ions โ hyperpolarization of the nerve or muscle cell โ flaccid paralysis and death of the parasite. * **Secondary Mechanism:** Enhances the release of **gamma-aminobutyric acid (GABA)** at presynaptic neurons. GABA acts as an inhibitory neurotransmitter โ blocks post-synaptic stimulation โ paralysis. > **Pharmacology Pearl:** Because flukes (trematodes) and tapeworms (cestodes) do not utilize GABA as a peripheral nerve transmitter and lack glutamate-gated chloride channels, ivermectin is completely ineffective against these parasites. Mammals generally lack glutamate-gated chloride channels, and mammalian GABA receptors are confined to the CNS, which ivermectin does not readily cross (unless the P-glycoprotein pump is defective or overwhelmed), providing a wide margin of safety.
Dosing by species
- As a preventative for heartworm ยท 0.024 mg/kg (24 micrograms/kg) PO every 30-45 days ยท PO ยท every 30-45 days ยท Also controls hookworms at this dosage.
- For Aelurostrongylus abstrusus ยท 0.4 mg/kg SC once ยท SC ยท once
- Ear mites ยท 1 mg/g ear gel ยท topical ยท Not specified ยท Not specified ยท Otimectin Vet. Do not use in kittens under 16 weeks.
- For susceptible parasites ยท 300 micrograms/kg (0.3 mg/kg) SC in the neck immediately behind the ear ยท SC ยท once
- For general control of endo- and ectoparasites in potbellied pigs ยท 300 micro-grams/kg SC or IM once for internal parasites and repeated in 10-14 days for external parasites ยท SC/IM ยท once, repeat in 10-14 days ยท Only partially effective against whipworms.
- For prevention of heartworm disease ยท 0.02 mg/kg PO monthly ยท PO ยท monthly
- To treat heartworm disease using the very slow protocol ยท 50 micrograms PO once a month. ยท PO ยท once a month
- For nasal bot infection ยท 200 micrograms/kg ยท SC/PO ยท once
- For susceptible parasites ยท 200 micrograms/kg SC for one dose ยท SC ยท once
Routes of administration
Contraindications
- Foals less than 4 months old (manufacturer recommendation)
- Puppies less than 6 weeks old
- Breeds susceptible to ABCB1-1ฮ (MDR1) mutation at high doses (unless tested normal)
- Chelonians (turtles, tortoises)
- Indigo snakes
- Skinks
- Lactating dairy animals (no milk withdrawal established)
- Females of breeding age (cattle/swine, per label)
- Dogs with the MDR1 (ABCB1) gene mutation (unless using strictly at low heartworm preventative doses)
- Chelonians (turtles and tortoises) - causes fatal flaccid paralysis
- Kittens under 16 weeks of age (for topical ear gel)
- Use of concentrated livestock formulations in small animals
Adverse effects
- Horses: Ventral midline swelling and pruritus (hypersensitivity to dying Onchocerca microfilariae)
- Dogs: Shock-like reaction (when used as microfilaricide), depression, hypothermia, vomiting
- Dogs (MDR1/Toxicity): Ataxia, lethargy, hypersalivation, mydriasis, tremors, seizures, blindness, coma
- Cats: Agitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, disorientation, blindness
- Cattle: Paralysis/staggering or salivation/bloat (if Hypoderma bovis larvae are killed in vital areas), injection site swelling
- Birds: Lethargy, anorexia, death (especially in finches and budgerigars)
- Neurotoxicity (ataxia, tremors, mydriasis, blindness, coma, death) - especially in MDR1-mutant dogs
- Hypersalivation
- Vomiting
- Lethargy
- Bradycardia
Drug interactions
- Benzodiazepines ยท Effects may be potentiated by ivermectin; concurrent use is not advised.
- Ketamine ยท Avoid ivermectin in reptiles within 10 days of ketamine administration.
- Spinosad ยท Increased risk of neurotoxicity; do not use with high extra-label doses of ivermectin. ยท major
- Amiodarone ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Carvedilol ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Clarithromycin ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Cyclosporine ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity. ยท moderate
- Diltiazem ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Erythromycin ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Itraconazole ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
- Ketoconazole ยท Strong P-glycoprotein inhibitor; should never be used with ivermectin in dogs. ยท moderate
- Quinidine ยท P-glycoprotein inhibitor; increases risk of ivermectin CNS toxicity.
Monitoring
- Clinical efficacy (resolution of parasites, negative skin scrapes, etc.)
- Adverse effects/toxicity (especially neurologic signs: ataxia, mydriasis, tremors)
- MDR1 (ABCB1) genotype (prior to use in susceptible breeds)
- Neurological signs (ataxia, mydriasis, tremors)
- Resolution of parasitic infection
Overdose
**Clinical Signs of Toxicity:** * **Dogs:** Vomiting, ataxia, lethargy, tachycardia, hypersalivation, mydriasis, tremors, and seizures. In non-sensitive breeds, signs rarely occur at โค 1 mg/kg. Mydriasis occurs at 2.5 mg/kg, tremors at 5 mg/kg, severe tremors/ataxia at 10 mg/kg. LD50 is 80 mg/kg. In MDR1-sensitive breeds, severe signs can develop within 4 hours at much lower doses. * **Cats:** Agitation, vocalization, anorexia, mydriasis, rear limb paresis, tremors, disorientation, blindness, head pressing, wall climbing. Margin of safety is narrower in kittens (signs seen at 300 mcg/kg). * **Large Animals:** Horses show visual impairment, depression, ataxia at 2 mg/kg. Cattle show ataxia and listlessness at 8 mg/kg. Swine show lethargy, ataxia, tremors, lateral recumbency at 30 mg/kg. **Treatment:** * **Decontamination:** Emptying the gut should be considered for recent massive oral ingestions. Repeated doses of activated charcoal are advised to interrupt enterohepatic recirculation. * **Supportive Care:** Symptomatic and supportive therapy for CNS, GI, and cardiovascular effects. * **Advanced Therapy:** **Intravenous Lipid Emulsion (IVFE)** therapy has been used successfully to facilitate clearance of ivermectin due to its highly lipophilic nature.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.