WHO Acute Hazard classification: Not listed

Mechanism of Action of Emodepside

Emodepside has a molecular mode of action that is different from the one of most other anthelmintics. It binds to so-called latrophilin receptors in neuromuscular junctions of the worm muscle cells. There is also evidence that it interferes with the potassium channels in the neuronal membranes. The bottom line for the parasites is that they are paralyzed and die or are expelled.

In mammals, including dogs and cats, these type of receptors are also found in the brain within the subgroup of the secretins. This explains the high sensitivity of dogs with the MDR-1 mutation to emodepside. In these dogs emodepside can more easily cross the blood-brain barrier as it happens with macrocyclic lactones (e.g. ivermectin). 

Toxicity and Tolerance of Emodepside

  • LD50 acute in rats: p.o. >500 mg/kg
  • LD50 acute in rats: dermal >5000 mg/kg
  • Cats, both young and adults tolerate without toxic symptoms up to 6 treatments with a combination of emodepside + praziquantel every 2 weeks at up to 5x the therapeutic dose. 
  • Cats, treated at 10x the therapeutic dose showed sight salivation (drooling), trembling and depression that resolved 24 hours after treatment.
  • After oral administration of the commercial product to cats (usual administration is topical) all animals showed drooling and vomit. 
  • Dogs tolerated orally administered emodepside very well. In ivermectin-sensitive Collies the therapeutic margin of emodepside is significantly lower. Treatment at 2x the therapeutic dose can cause symptoms such as discomfort and uncertain gait. 

Toxic Symptoms caused by Emodepside

  • Most frequently reported symptoms of intoxication with emodepside are hypersalivation (drooling), vomit, trembling and depression.
  • Severe intoxications affect mainly the CNS (Central Nervous System).

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

  • At therapeutic doses the following adverse drug reactions have been reported: licking and excess grooming, scratching at the treatment site, salivation (drooling), lethargy, hair loss, transient tremor (uncoordinated trembling or shaking movements), ataxia (uncoordinated movements), stupor (daze) have been observed, vomit and diarrhea.
  • Do not use tablets for dogs in cats, and never use tablets for large dogs in small dogs. It happens that some users want to save money buying tablets for large dogs 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 emodepside and macrocyclic lactones or other drugs that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates 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.
  • Emodepside treatment can have some efficacy against heartworms (Dirofilaria spp.) although it is not approved for its control or prevention. Therefore complications cannot be excluded in dogs (more rarely in cats) infected with these parasites. Read the corresponding article on Dirofilaria spp in this site.

Antidote and Treatment of Emodepside Intoxication

  • There is no antidote for metaflumizone poisoning.
  • Treatment consists in supportive and symptomatic measures.

Pharmacokinetics of Emodepside

  • Following topical administration emodepside is absorbed slowly into the bloodstream. Maximum plasma levels are reached 2-3 days after treatment. Absorption after oral administration is higher if administered to fasted animals. Bioavailability after oral administration is ~50%. Emodepside is distributed throughout the whole organism, but highest concentrations are found in fat tissues, where it forms a deposit that is slowly released.
  • Excretion is slow: halftime after topical administration to cats is ~9 days. In rats, about 45-55% of the administered dose is excreted unchanged, mainly through the feces, the rest in the form of numerous metabolites.

Environmental Toxicity of Emodepside

  • Emodepside is toxic to aquatic invertebrates.
  • Not being used on livestock, agriculture or public hygiene, knowledge on its environmental fate and impact is very scarce. Nevertheless, it can be assumed that correctly used in dogs and cats the risk of environmental pollution due to emodepside is very low.

Additional information

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

  • Emodepside belongs to the chemical class of the depsipeptides.
  • Emodepside is not used in livestock
  • Emodepside is not used in human medicines.
  • Emodepside is not used in crop pesticides.
  • Emodepside 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 emodepside.


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.