WHO Acute Hazard classification: Not listed

Mechanism of Action of Moxidectin

As all macrocyclic lactones, moxidectin acts as agonist of the GABA (gamma-aminobutyric acid) neurotransmitter in nerve cells and also binds to glutamate-gated chloride channels in nerve and muscle cells of invertebrates. In both cases it blocks the transmission of neuronal signals of the parasites, which are paralyzed and expelled out of the body, or they starve. It also affects the reproduction of some parasites by diminishing oviposition or inducing an abnormal oogenesis.

In mammals the GABA receptors occur only in the central nervous system (CNS), i.e. in the brain and the spinal chord. But mammals have a so-called blood-brain barrier that prevents microscopic objects and large molecules to get into the brain. Consequently macrocyclic lactones are much less toxic to mammals than toparasites without such a barrier, which allows quite high safety margins for use on livestock and pets. A notable exception to this are dog breeds that carry the MDR-1 gene defect (see later).

Toxicity and Tolerance of Moxidectin

  • LD50 acute, rat, p.o. 106 mg/kg
  • LD50 acute, rat, dermal >2000 mg/kg
  • In dogs without the MDR-1 gene defect a single oral dose of 1120 mcg/kg, 300x the therapeutic dose as a heartworm (Dirofilaria spp) preventative, caused no undesirable adverse drug reactions.
  • Dogs with the MDR-1 gene defect tolerate moxidectin better than ivermectin. Subcutaneous doses of 30, 60 y 90 mcg/kg moxidectin (10x 20x y 30x the therapeutic dose as a heartworm (Dirofilaria spp) preventative showed no neurotoxic effects. 
  • In adult dogs without the MDR-1 gene defect a weekly administration of 5x the therapeutic dose as a spot-on during 17 weeks showed no adverse drug reactions. 
  • In adult cattle, no clinical symptoms or pathologic effects were recorded after daily pour-on administration of 5x the recommended dose during 5 consecutive days, 10x the recommended dose during 2 consecutive days, or 25x the recommended dose one day.
  • In young cattle, however, 3x the recommended dose can already cause neurotoxic signs due to overdose: ataxia (uncoordinated movements), salivation (drooling), tremor (uncoordinated trembling or shaking movements), depression, weakness, etc. These symptoms usually disappear after 24 to 48 hours. 
  • Young horses, particularly newly born foals, showed typical neurotoxic symptoms after slight overdose, which can be fatal. Probably because the blood-brain barrier is not completely developed in newborns.
  • As a general rule, cattle, sheep, goats and horses tolerate moxidectin very well at the therapeutic dose.

Toxic Symptoms caused by Moxidectin Poisoning

General symptoms

  • The symptoms of moxidectin poisoning are similar to those of ivermectin poisoning and are the consequence of an excessive concentration of the molecule in the CNS (Central Nervous System) and the subsequent increase of GABA activity. Moxidectin stimulates the release of the GABA neurotransmitter (gamma-Aminobutyric acid) in the presynaptic neurons and enhances its postsynaptic binding to its receptors. This increases the flow of chloride ions in the neurons, which causes hyperpolarization of the cell membranes. This on its turn disturbs normal nervous functions and causes a general blockage of the stimulus mechanisms in the CNS. The resulting cerebral and cortical deficits include mainly
    • Ataxia (uncoordinated movements)
    • Hypermetria (excessive or disproportionate movements)
    • Disorientation
    • Hyperesthesia (excessive reaction to tactile stimuli)
    • Tremor (uncoordinated trembling or shaking movements)
    • Mydriasis (dilatation of the pupils); in cattle and cats also myosis (contraction of the pupils)
    • Recumbency (inability to rise)
    • Depression
    • Blindness
    • Coma (persistence unconsciousness)
  • As a general rule, young animals are more sensitive to overdosing, react stronger, and prognosis is worse than for adult animals. 
  • Besides erroneous dosing, overdosing can occur due to excessive licking after pour-on delivery to livestock (usually licking of other animals in the same herd) or spot-on delivery to dogs and cats (particularly in cats due to intense grooming).
  • Frequent administration errors in livestock include intramuscular or intravenous instead of subcutaneous injection. This results in excessive blood levels. Another frequent error is repeated unintended treatment in short intervals due to animal mistaking.
  • A frequent administration error in dogs is erroneous partial administration to small dogs of tablets or spot-ons approved for large dogs.
  • A frequent administration error in cats is erroneous partial administration to cats of tablets or spot-ons approved only for dogs.

Poisoning Symptoms in Dogs

  • In dogs without the MDR-1 gene defect, the dominant macrocyclic lactones poisoning symptom is extreme mydriasis (dilatation of the pupils) together with incomplete and deregulated pupillary reflex. Mydriasis in both eyes is the most sensitive indicator of ivermectin and other macrocyclic lactones intoxication, and the most frequent symptom in dogs. 
  • At higher doses and in dogs with the MDR-1 gene defect other symptoms have been observed as well: weakness, lethargy, hypothermia (too low body temperature), hypersalivation (drooling), vomit, difficult breathing, behavioral disturbances, confusion, seizure, death.
  • Symptoms develop usually 5 to 24 hours after treatment and can last for several days until coma. As a general rule, poisoning is more serious and prognosis is worse if the symptoms develop faster.

Poisoning Symptoms in Cattle

  • Most frequent symptoms in cattle are general depression of the CNS (Central Nervous System), including deafness and ataxia (uncoordinated movements).
  • Calves can show poisoning symptoms at doses only 3x the therapeutic dose. They include ataxia (uncoordinated movements), hypermetria (excessive or disproportionate movements) and tremor (uncoordinated trembling or shaking movements). Colics have also been reported. Deaths cannot be excluded.

Moxidectin Side Effects, Adverse Drug Reactions (ADRs) and Warnings

  • In dogs the following ADRs have been reported after moxidectin treatment at the therapeutic dose: Ataxia (uncoordinated movements), lethargy, loss op appetite, vomit, diarrhea and hives. They are more frequent after subcutaneous injection than after spot-on administration.
  • After moxidectin injection swelling may develop at the injection site. It usually disappears in a few days.
  • In horses, the risk of Chlostridium infection after injection is particularly high. If left untreated such infections are fatal. This was experienced with ivermectin but it is not related to ivermectin, but to the use of contaminated needles. For this reason in most countries macrocyclic lactones (moxidectin, ivermectin, etc.) for horses are usually available only for oral delivery (pastes, gels, etc.) and not as an injectables.
  • Moxidectin should not be administered to calves younger than 8 weeks and foals younger than 4 months.
  • Never use spot-ons or tablets for dogs in cats, and never use spot-ons or tablets for large dogs in small dogs. It happens that some users want to save money buying large tablets or spot-ons for treating smaller dogs (or even cats!) twice or more times. The risk of overdosing is considerable, either due to erroneous calculations or to unskilled manipulation. In addition, dog medicines may sometimes contain ingredients that are toxic to cats.
  • WARNING: Dogs of some breeds are sensitive to moxidectin, other macrocyclic lactones or other drugs (e.g. emodepside) that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates slightly higher than the recommended ones. Consequently dosing must be as accurate as possible. This is the case for Collies and related breeds, which have a mutation in the MDR-1 gene that affects the blood-brain barrier and makes it more permeable to such compounds than in dogs without this mutation. Besides Collies, other dog breeds have shown similar problems, although the MDR-1 mutation has not been confirmed in all of them. The breeds more affected by this mutation are (% frequency): Collie (70%), Long-haired Whippet (65%), Australian Shepherd (50%, also mini),  McNab (30%), Silken Windhound (30%), English Shepherd (15%), Shetland Sheepdog (15%), English Shepherd (15%), German Shepherd (10%), Herding Breed Cross (10%). Other less affected breeds are: Old English Sheepdog, Border Collie, Berger Blanc Suisse, Bobtail, Wäller. The only way to be sure that a dog is affected or not by the MDR-1 gene defect is to test for it. As more dogs are tested it is likely that the mutation is discovered in other breeds, or that the frequencies change.
  • Complications in dogs due to Dirofilariasis (heartworm infection)
    • Most products with moxidectin and other macrocyclic lactones are effective against heartworm larvae in the blood. Heartworm infection (Dirofilaria spp) is a common disease in dogs in regions with hot or mild weather. The disease is called dirofilariasis and is transmitted by mosquitoes. It is less frequent in cold regions but can occur there as well. Cats and horses can be affected too. Heartworm preventatives hinder larvae (microfilariae) in the pet's blood to develop to adult worms. The sudden death of microfilariae releases enormous amounts of allergens that can cause an allergic shock. The following symptoms may develop about 5 hours after treatment: pale mucosae, tachypnea (rapid breathing), dispnea (difficult breathing), vomit, weak and accelerated pulse, weakness, fever and ataxia (uncoordinated movements). Therapy requires shock treatment, including administration of corticosteroids and fluid supply.
    • Another possible complication is that treatment at the therapeutic dose against microfilariae can also kill some adult worms, if not all. Now, dead adult worms or their remains in the heart or in the pulmonary artery can physically obstruct the pulmonary blood vessels with the consequent damage to the lungs, which can be fatal. This means that any dog that is treated with a macrocyclic lactone should be checked for already existing heartworm infection. If the check is positive, the heartworm infection has to be treated with other specific heartworm products under strict supervision of a veterinary doctor.
  • Unless prescribed by a veterinary doctor, never use in dogs or cats products for livestock that are not explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to ingredients that are not tolerated by pets or are even toxic to them.

Antidote and Treatment of Moxidectin Intoxication

  • There is no antidote for moxidectin poisoning.
  • Treatment consists in supportive and symptomatic measures.
  • Most patients recover in 7 to 10 days, but recovery of comatose patients usually needs longer.
  • It can be helpful to read the safety summary for ivermectin, the most used macrocyclic lactone.

Pharmacokinetics of Moxidectin

After absorption into blood moxidectin is well distributed throughout the whole body including target organs such as the gastric and gut mucosae. The highest concentrations are found in body fat that acts as a depot from where it is progressively released to blood. Moxidectin is more lipophilic than ivermectin and consequently it is stronger deposited in body fat, which results in a higher residual effect and a longer protection against several parasites than ivermectin (by comparable delivery form and administered dose).

On sheep, the subcutaneous injection provides a significantly longer protection than the pour-on.

Environmental Toxicity of Moxidectin

  • Moxidectin is highly toxic to fish and extremely toxic to invertebrates. For this reason disposal of moxidectin remains (e.g. in empty containers) in watercourses must be absolutely avoided. There is a certain environmental risk of water pollution from run-off after pour-on administration to large cattle herds.
  • Moxidectin is highly toxic to aquatic invertebrates and fish, but only slightly toxic to birds. For this reason disposal of moxidectin residues (e.g. in empty containers) in watercourses must be absolutely avoided. There is a certain environmental risk of water pollution from run-off after pour-on administration to large cattle herds. 
  • Moxidectin is poorly soluble in water. Sunlight quickly degrades moxidectin solved in water. Half-life in water is ~7 hours.
  • Soil microorganisms break down moxidectin. Biotransformation half-life in soil is ~60 days.
  • Moxidectin does not bioaccumulate.
  • >Moxidectin administered to livestock is partially excreted in the feces and has a negative impact on coprophagous invertebrates (fly larvae, dung beetles, etc.) that feed or breed on dung of cattle or other livestock. Studies in feedlots concluded that the use of moxidectin on livestock is not detrimental for soil organisms.

Additional information

Click here for a list and overview of all safety summaries of antiparasitic active ingredients in this site.

  • Moxidectin belongs to the chemical class of the macrocyclic lactones.
  • Moxidectin is not used in human medicines.
  • Moxidectin is not used in crop pesticides.
  • Moxidectin is not used in biocides for public or domestic hygiene.
  • Click here for General safety of antiparasitics for domestic animals.
  • Click here for General safety of antiparasitics for humans.
  • Click here for General safety of antiparasitics for the environment.
  • Click here for technical and commercial information on moxidectin.


If you intend to use a veterinary drug containing this active ingredient you must carefully read and follow the safety instructions in the product label.  Always ask your veterinary doctor, or pharmacist, or contact the manufacturer. Be aware that the safety instructions for the same veterinary medicine may vary from country to country.

The information in this page must not be confused with the Materials and Safety Datasheets (MSDS) officially issued by manufacturers for active ingredients and many other chemicals. MSDSs target safety during manufacturing, transport, storage and handling of such materials. This safety summary is a complement to the information on product labels and MSDS.

The toxicity of an active ingredient must not be confused with the toxicity of finished products, in this case parasiticidal drugs or pesticides. Finished products contain one or more active ingredients, but also other ingredients that can be relevant from the safety point of view.

All information in this site is made available in good faith and following a reasonable effort to ensure its correctness and actuality. Nevertheless, no this regarding guarantee is given, and any liability on its accuracy, integrity, sufficiency, actuality and opportunity is denied. Liability is also denied for any possible damage or harm to persons, animals or any other goods that could follow the transmission or use of the information, data or recommendations in this site by any site visitor or third parties.