WHO Acute Hazard classification: Not listed.

Mechanism of action of Fenbendazole

The molecular mode of action of all benzimidazoles, including fenbendazole, 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 Fenbendazole

• LD50 acute, rats, p.o > 10000 mg/kg
• LD50 acute, cattle, p.o 750 mg/kg
• Livestock, pets and poultry usually tolerate fenbendazole very well.
• Safety margin (usual therapeutic dose in cattle & sheep: 5 to 10 mg/kg; in dogs and cats 20 to 50 mg/kg):
• Cattle ≥20
• Sheep: ≥500
• Horses: ≥100
• Dogs: ≥10
• Cats: ≥3
• Pigeons: 3
  

Toxic Symptoms caused by Fenbendazole Poisoning

• As a general rule, poisoning with fenbendazole is quite unusual, due to its low toxicity, the high safety margins and the fact that most species tolerate it very well.
• In pigs, doses of 125 mg/kg/day during 5 days or 2000 mg/kg during 15 days caused reversible leukopenia that resolved after 15 days.
• In pregnant bitches teratogenic effects were reported after treatment at 3x the recommended dose.
• In young pigeons fenbendazole at therapeutic doses can cause plumage damage.

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

• Dogs and cats showed occasional vomit after treatment at the therapeutic dose.
  
• Bitches and queens shouldn't be treated with fenbendazole during pregnancy.
• Pregnant sows shouldn't be treated with fenbendazole during the first 3 months of gestation.
• Birds shouldn't be treated with fenbendazole during molting.
• Allergic reactions can occur due to sudden death of worms and subsequent release of large amounts of allergens. It has been observed mainly after treatment against larva migrans caused by Strongylus vulgaris.
• Simultaneous administration with bromsalan derivatives (flukicides now vastly abandoned) can cause acute intoxications in cattle and sheep.
• Never use tablets (or suspensions, pastes, etc.) for dogs in cats or tablets for large dogs in 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 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 Fenbendazole Intoxication

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

Pharmacokinetics of Fenbendazole

Fenbendazole is very poorly soluble in water. Orally administered fenbendazole is poorly absorbed into the bloodstream. Therefore it is very important that it remains as long as possible in the rumen, to form a reservoir from which it is progressively solved and absorbed. Direct administration into the abomasum (e.g. due to the "oesophageal groove reflex") strongly diminishes the absorption and consequently its efficacy.

Absorbed fenbendazole is metabolized in the liver to its sulfoxide derivative, which is identical with oxfendazole, another veterinary anthelmintic benzimidazole. Interestingly, the oxfendazole produced through metabolism is released back to the rumen, where the bacterial flora reduces it back to fenbendazole. This increases the bioavailability of fenbendazole in ruminants.

Excretion occurs mainly through feces. In cattle and sheep, 6 days after oral administration about 35% of the ingested dose is excreted unchanged, and about 5% metabolized. A small amount is excreted through urine, mainly in the form of various metabolites. Excretion in goats is about twice as fast as in sheep.

In dogs, cats and birds, the absence of such a reservoir as in ruminants strongly shortens the residual effect, which may require a higher dose or more frequent treatments to achieve the desired efficacy. In dogs, 48 hours after administration fenbendazole is not detectable in blood plasma, in birds 36 hours, and in cats 7 days.

Influence of diet. In ruminants, reducing the amount of feed slows down the exit flow of the rumen and prolongs the time the anthelmintic remains there and can be absorbed. Consequently it is advisable to reduce the animals' access to feed (especially to fresh pasture, not to water) 24 hours before administration. For the same reason, it is better to keep the animals away from food for about 6 hours after drenching. However sick, weak, or pregnant animals should not be kept away from food and fasting animals should have access to water. In cattle, a fiber-rich diet also increases the bioavailability of fenbendazole.

In contrast with this, in dogs and horses, administration of fenbendazole with the food increases the bioavailability of fenbendazole.

Influence of parasites. Heavy infestations with gastrointestinal roundworms reduce the bioavailability of fenbendazole in ruminants. The reason is that the inflamed wall does not properly regulate the pH (acidity) in the abomasum and the intestine, which has a negative influence on the solubility and the absorption of fenbendazole and on the distribution of its metabolites. In addition, the passage of food through the stomach is also faster in case of heavy infestations, which reduces the bioavailability of the anthelmintic.

Environmental Toxicity of Fenbendazole

• 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 fenbendazole 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.

• Fenbendazole belongs to the chemical class of the benzimidazoles.
• Fenbendazole is not used in human medicines.
  
• Fenbendazole is not used in crop pesticides.
• Fenbendazole 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 fenbendazole.