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EPRINOMECTIN: Safety Summary for Veterinary Use

WHO Acute Hazard classification: Not listed


Mechanism of Action of Eprinomectin

As all macrocyclic lactones, eprinomectin 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 the parasites that do not have 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 Eprinomectin

  • LD50 acute, mouse, p.o. 70 mg/kg
  • LD50 acute, rat, p.o. 55 mg/kg
  • In tolerance studies on cattle, animals treated topically (pour-on) 3 times at 1x, 3x, and 5x the therapeutic dose in intervals of 7 days, or animals treated once at 10x the therapeutic dose didn't shoe toxic side effects.
  • In tolerance studies on cattle, animals treated with the extended-release injectable at up to 5x the therapeutic dose tolerated the treatments very well. Injection site reactions included occasional swelling without pain.
  • As a general rule, cattle tolerate treatment with eprinomectin very well.

Toxic Symptoms caused by Eprinomectin Poisoning

  • The symptoms of eprinomectin 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. Eprinomectin 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.
  • The following intoxication symptoms have been reported for eprinomectin in toxicity studies on laboratory animals (rodents, rabbits, etc.): ataxia (uncoordinated movements), mydriasis (dilatation of the pupils), salivation (drooling) and tremor (uncoordinated trembling or shaking movements).

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

  • After eprinomectin injection swelling may develop at the injection site. It usually recedes in a few days.
  • There are very few reports on ADRs to eprinomectin on cattle treated at the therapeutic dose.
  • In most countries eprinomectin is only approved for use on cattle. Consequently reliable data on its safety when used on other domestic animals is very scarce.
  • 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).
  • Potential 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.

Antidote and Treatment of Eprinomectin Intoxication

  • There is no antidote for eprinomectin 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 Eprinomectin

  • After topical administration (pour-on) to cattle only about 46% of the administered dose is absorbed through the skin, the rest remains outside and breaks down slowly or is washed away. The halftime for absorption in dairy cows is about 0.95 days. Most of the administered dose is absorbed in the first 7 to 10 days after treatment, but absorption continues until 17 to 21 days. Peak plasma concentrations are reached 2 to 5 days after treatment.
  • After treatment with the extended-release injectable a polymeric PLGA [poly(lactic-co-glycolic) acid] matrix is formed in the subcutanous tissue. The active ingredient is slowly released from the matrix into the bloodstream maintaing effective parasiticidal blood levels for months.
  • Once absorbed into blood eprinomectin is poorly metabolized in the bovine's organism. It is well distributed throughout the host's body and the maximum concentrations are found in liver and kidneys. After pour-on administration, eprinomectin does not appear in milk and this is why it is the only macrocyclic lactone approved for use on dairy cows (only the pour-on formulation!). Metabolism after treatment with the extended-release injectable is also scarce.
  • Eprinomectin is excreted mainly through the feces, only a very small portion through the urine.
  • After topical administration to cats, te maximum concentrations were reached 24h after dosing. The average terminal half-life was 114 h due to slow absorption. Eprinomectin was widely distributed. Topical eprinomectin was absorbed with an average absolute bioavailability of 31%. Absorbed eprinomectin it is  highly bound to protein (>99%), and thus likely to be excreted mainly as unchanged parent drug in the feces of cats.

Environmental Toxicity of Eprinomectin

  • Eprinomectin is highly toxic to fish and extremely toxic to invertebrates. For this reason disposal of eprinomectin 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.
  • Eprinomectin is poorly soluble in water. Sunlight quickly degrades eprinomectin in water. Half-life in water is ~1 day.
  • Soil microorganisms break down eprinomectin, with a half-life of ~65 days at ~22°C.
  • Eprinomectin does not bioaccumulate.
  • Eprinomectin 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. However, impact studies concluded that eprinomectin use (both as a pour-on and as an extended-release injectable) can be used safely without impact on the environment.

Additional information

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

  • Eprinomectin belongs to the chemical class of the macrocyclic lactones.
  • Eprinomectin is not used in dogs and cats.
  • Eprinomectin is not used in human medicines.
  • Eprinomectin is not used in crop pesticides.
  • Eprinomectin 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 here for technical and commercial information on eprinomectin.

WARNING

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.

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