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MEBENDAZOLE: Safety Summary for Veterinary Use

WHO Acute Hazard classification: Not listed.


Mechanism of action of Mebendazole

The molecular mode of action of all benzimidazoles, including mebendazole, consists in binding to tubulin, a structural protein of microtubules. These microtubules are important organelles involved in the motility, the division and the secretion processes of cells in all living organisms. In the worms the blocking of microtubules perturbs the uptake of glucose, which eventually empties the glycogen reserves. This blocks the whole energy management mechanism of the worms that are paralyzed and die or are expelled.

Since cell division is also disturbed, worm egg production and development is also blocked by benzimidazoles, i.e. most of them also have an ovicidal effect.


Acute Toxicity and Tolerance of Mebendazole

  • LD50 acute, rats, p.o. > 1280 mg/kg
  • LD50 acute, dogs, cats, rabbits, p.o. >680 mg/kg
  • Safety margin in sheep and goats > 20
  • Therapeutic margin in horses 40-90, dogs and cats ~25
  • Doses tolerated without toxic symptoms:
    • Cattle: 80 mg/kg p.o.
    • Horses: 350-400 mg/kg p.o.
    • Sheep: 320 mg/kg
  • As a general rule dogs, cats, livestock and horses tolerate mebendazole very well, usually without adverse drug reactions.
  • Terrestrial gallinaceous birds (chicken pheasants, turkey, etc.) tolerate mebendazole very well. This is not the case for aquatic and wild birds: at the therapeutic dose hemorrhagic enteritis and death can happen. Cormorants, pelicans and birds of prey are particularly sensitive. Birds of prey can suffer toxic hepatitis.
  • In sub-chronic studies, dogs treated at 2.5, 10 and 40 mg/kg 6 days a week during 13 weeks showed no toxic symptoms.
  • Horses tolerated doses of 5 mg/kg/day during 19 to 74 weeks and doses of 52.5 mg/kg/day during 15 days without toxic symptoms.
  • Sheep tolerated doses of 60 mg/kg/day during 5 days without clinical or pathological symptoms.
  • Laying hens treated at 125 ppm (=mg/kg) mixed with the feed during 30 days showed no toxic symptoms and laying performance was not reduced.

Toxic Symptoms caused by Mebendazole Poisoning

  • As a general rule, poisoning with mebendazole is quite unusual, due to its low toxicity, the high safety margins and the fact that most species tolerate it very well.
  • After heavy overdose hepatic damage was observed in rats, dogs and cats.
  • Rodents showed teratogenic effects at high doses, but not so rabbits, horses, sheep or swine.

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

  • In dogs, the most frequent adverse drug reactions at the therapeutic dose are vomit and diarrhea.
  • Some studies in dogs showed hepatic damage (acute diffuse necrosis) already at the therapeutic dose. Repeated or prolonged use increases its incidence. The symptoms appeared between 1 and 14 days after treatment as jaundice, vomit, depression, anorexia and increased plasmatic ALT levels. However, other studies could not reproduce such results.
  • In birds, high doses of mebendazole can negatively influence reproduction. Therapeutic doses can disturb molting.
  • In quails and pheasants mebendazole treatment can impair laying performance and egg hatching.
  • Mebendazole should not be administered to sick or weak horses.
  • Mebendazole administration to animals with hepatic damage must be done with utmost care.
  • Never use tablets (or suspensions, pastes, etc.) for dogs on cats, or tablets for large dogs on small dogs. It happens that some users want to save money buying large tablets 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.
  • Unless prescribed by a veterinary doctor, never use on 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 Mebendazole Intoxication

  • There is no specific antidote for mebendazole.
  • Treatment consists in supportive and symptomatic measures.
  • After oral intoxication gastric lavage is recommended, as well as administration of active charcoal.

Pharmacokinetics of Mebendazole

Mebendazole is very poorly soluble in water. Orally administered mebendazole is poorly absorbed into the bloodstream: ~30% in pigs, and <10% in dogs. This means that significant amounts remain in the gastrointestinal tract and are available for the control of gut dwelling roundworms and tapeworms.

Absorbed mebendazole is quickly broken down in the liver to metabolites without anthelmintic efficacy. Both the parent molecule and its metabolites are excreted mainly through bile and feces, the rest through urine. However, there are important species-specific differences. Whereas in dogs >90% od the administered dose is excreted through feces, up to 50% is excreted through urine in swine.

Influence of parasites. Heavy liver fluke infestations in sheep slow down the metabolism of mebendazole in the liver, which increases its bioavailability and prolongs the residence time. This may require longer withholding periods.


Environmental Toxicity of Mebendazole

  • Not being used in crop pesticides or in public hygiene, knowledge on its environmental fate and impact is very scarce.
  • Nevertheless, it can be assumed that correctly used in dogs, cats and livestock mebendazole is unlikely to be detrimental for the environment, including coprophagous insects.

Additional information

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

  • Mebendazole belongs to the chemical class of the benzimidazoles.
  • Mebendazole is used in human medicines.
  • Mebendazole is not used in crop pesticides.
  • Mebendazole is not used in public or domestic hygiene as a biocide.
  • 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 mebendazole.

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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