WHO Acute Hazard classification: Not listed

Mechanism of Action of Doramectin

As all macrocyclic lactones, doramectin 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 to parasites 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.

Toxicity and Tolerance of Doramectin

  • LD50 acute, rat, p.o. in aqueous vehicle: 550 to 2000 mg/kg
  • LD50 acute, rat, p.o. in lipid vehicle: 50 to 200 mg/kg
  • LD50 acute, rabbit, dermal (in lipid vehicle) >2000 mg/kg
  • Safety margin:
    • Adult cattle: ~25
    • Pregnant cows, calves: ~3
  • In cattle, s.c. injection or pour-on treatment at 5x the therapeutic dose during 3 consecutive days didn't cause symptoms of intolerance.
  • As a general rule, cattle, sheep, goats and swine tolerate doramectin very well at the therapeutic dose.
  • Since it is not approved for use in dogs, cats and horses in most countries, little is known about doramectin's tolerance and safety for these animals.

Toxic Symptoms caused by Doramectin Poisoning

General symptoms

  • The symptoms of doramectin 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. Doramectin 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. 

Poisoning Symptoms in Dogs

  • Off-label use of doramectin in dogs is likely to lead to adverse drug reactions, and fatalities cannot be excluded. Dogs with the MDR-1 defect treated with doramectin at a dose of 0.7 mg/kg (s.c.) showed the typical neurotoxic symptoms of ivermectin intolerance: ataxia (uncoordinated movements), hipersalivation (drooling), hiperventilation (fast breathing), lethargy, depression, drowsiness, tremor (uncoordinated trembling or shaking movements), etc. The animals recovered 5 to 15 days after treatment.

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

  • After doramectin injection swelling may develop at the injection site. It usually recedes in a few days.
  • The risk of complications after off-label use on dogs, cats or horses is higher than after using ivermectin. Among other reasons because little is known about the correct dosing of doramectin for these animals: not been approved for dogs, cats and horses the safety of doramectin for these animals has not been thoroughly investigated.
  • 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).
  • Frequent administration errors in livestock include intramuscular or intravenous instead of subcutaneous injection. Another frequent error is repeated unintended treatment in short intervals due to animal mistaking. Such errors result in excessive blood levels.
  • 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 Doramectin Intoxication

  • There is no antidote for doramectin poisoning.
  • Treatment consists in supportive and symptomatic measures.
  • It can be helpful to read the safety summary for ivermectin, the most used macrocyclic lactone.

Pharmacokinetics of Doramectin

  • Halftime for absorption into blood after injection in a sesame oil vehicle is shorter for goats (~0.7 days) than for cattle (~2.4 days) or sheep (~2.7 days).
  • Doramectin 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. Bioavailability of doramectin after injection is almost 100%, but only about 18% after pour-on administration, which requires a higher dose.
  • Excretion goes through bile and feces, 50 to 70% in the form of the unchanged parent molecule. The highest concentration in blood occurs 24 to 48 hours after administration.

Environmental Toxicity of Doramectin

  • Doramectin is highly toxic to fish and extremely toxic to invertebrates. For this reason disposal of doramectin 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.
  • Doramectin is poorly soluble in water. Sunlight quickly degrades doramectin solved in water. Half-life in water is ~5 hours.
  • Soil microorganisms break down doramectin. Biotransformation half-life in soil is 60-80 days.
  • Doramectin does not bioaccumulate.
  • Doramectin 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 on pig manure treated with doramectin concluded that such use 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.

  • Doramectin belongs to the chemical class of the macrocyclic lactones.
  • Doramectin is not used in human medicines.
  • Doramectin is not used in crop pesticides.
  • Doramectin 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 doramectin.


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.