WHO Acute Hazard classification: Not listed.

Mechanism of action of Oxibendazole

The main molecular mode of action of all benzimidazoles, including oxibendazole, 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.

In the worms the blocking of microtubules perturbs also 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 Oxibendazole

• LD50 acute, rats, p.o.: >10000 mg/kg
• LD50 acute, mice, p.o.: >32000 mg/kg
• LD50 acute, rabbits, dermal: >20000 mg/kg
• Livestock, horses and pets usually tolerate oxibendazole very well.
• In horses and ruminants no toxic effects were recorded when administered at 60x the therapeutic dose.
• Sheep tolerated unique oral doses of 300 a 600 mg/kg, or daily doses of 10 a 50 mg/kg/day during 5 days withou showing toxic symptoms.
• Cattle tolerated unique oral doses of up to 600 mg/kg, or daily doses of 30 a 75 mg/kg/day during 5 days withou showing toxic symptoms.
• In dogs no toxic effects were reported after daily doses of 3 to 30 mg/kg/day during 98 days.
• Puppies tolerated up to 640x the therapeutic dose without symptoms.
• In adult dogs treated at 1280x the therapeutic dose vomit, trembling and depression were observed.

Toxic Symptoms and Adverse Drug Reactions caused by Oxibendazole

• As a general rule, poisoning with oxibendazole is quite unusual, due to its low toxicity, the high safety margins and the fact that most species tolerate oxibendazole very well.
• Main symptoms of intoxication after high oral doses were vomit, depression and trembling.

Oxibendazole Contraindications and Incompatibiities

• Simultaneous administration of oxibendazole with diethylcarbamazine (antihelmintic used sometimes against filariasis, e.g. against heartworms) in dogs can cause acute or chronic periportal hepatitis, particularly if the patient suffers already from hepatic problems. This can cause anorexia (loss of apetite), vomit, diarrhea and weight loss, as well as high plasmatic ALP and ALT values. In this case treatment must be immediately interrupted and replaced by another compound.
• Do not administer to weak equines or animals otherwise affected by colic, toxaemia or infections.
• 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.

Antidote and Treatment of Oxibendazole Poisoning

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

Pharmacokinetics of Oxibendazole

As most benzimidazoles, oxibendazole is almost insoluble in water and orally administered is poorly absorbed into the bloodstream. This means that significant amounts remain in the gastrointestinal tract and are available for the control of gut-dwelling roundworms and tapeworms. But blood levels are low and efficacy against tissue-dwelling worms may be lower or insufficient.

Little information is available on the metabolism of oxibendazole. Following oral administration to sheep maximum plasma levels were recorded after 6 hours, and 24 hours later ~35% of the administered dose was already excreted through urine. Absorbed oxibendazole is broken down in the liver to metabolites without anthelmintic activity.

Blood levels depend strongly on the administered dose. In sheep and goats splitting the therapeutic dose during 3 consecutive days (each day 1/3 of the recommended dose) significantly increased bioavailabiblity and hence efficacy.

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 oxibendazole.

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

En carnivores and birds, residual effect is significantly shorter than  in ruminants, whoch may require repeated treatents or higher doses to achieve the desired anthelmintic effect.

Environmental Toxicity of Oxibendazole

• 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 oxibendazole 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.

• Oxibendazole belongs to the chemical class of the benzimidazoles.
• Oxibendazole is scarcely used in livestock, and scarcely to moderately used in pets and horses.
• Oxibendazole is not used in human medicines.
  
• Oxibendazole is not used in crop pesticides.
• Oxibendazole 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 oxibendazole.