WHO Acute Hazard classification: Not listed.

Mechanism of action of Oxfendazole

The molecular mode of action of all benzimidazoles, including oxfendazole, 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 Oxfendazole

• LD50 acute, rats, p.o.  >6400 mg/kg
• LD50 acute, dogs (Beagle), >1600 mg/kg
• Livestock and pets usually tolerate oxfendazole very well.
• Safety margin in cattle and sheep >20
• Therapeutic margin in horses: 10
• In sheep oral doses 50x the therapeutic dose caused loss of appetite, fever and diarrhea. Fatalities can happen.
• Dogs tolerate 6 mg/kg/day during 3 months with out toxic symptoms. 
• At high doses oxfendazole has embryotoxic effects on pregnant bitches. Sustained administration to pregnant bitches can cause malformations in puppies.
• In pregnant ewes repeated doses of 7.5, 10 and 15 mg/kg had no embryotoxic effects. But doses of 22.5 to 25 mg/kg (4.5x the therapeutic dose) on day 17 of gestation caused malformations or death of the embryo.
• In pregnant sows doses of 4.5 to 13.5 mg/kg repeated 4x during organogenesis and embryo implantation didn't cause malformations or behavioral changes in the newborn piglets.

Toxic Symptoms caused by Oxfendazole Poisoning

• As a general rule, poisoning with oxfendazole is quite unusual, due to its low toxicity, the high safety margins and the fact that most species tolerate oxfendazole very well.
• Main symptoms of intoxication after high oral doses are loss of appetite, diarrhea, fever, cramps, nausea, vomit and convulsions. Hepatic and epicardial hemorraghe can also happen.

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

• After treatment of pregnant bitches with oxfendazole against larva migrans of Toxocara canis and Ancylostoma caninum to prevent prenatal or galactogenic (through the milk) infection of puppies a significant weight reduction at birth was reported, as well as an increases of palatoschisis cases (cleft palate).
• Allergic reactions can occur due to sudden death of worms and subsequent release of large amounts of allergens.
• Treatment of sick or weak horses must be done with utmost care.
• Due to insufficient data it is recommended not to treat pregnant mares and bitches with oxfendazole.
• In horses simultaneous treatment with oxfendazole and dichlorvos caused toxic symptoms.
• Simultaneous administration with bromsalan derivatives (flukicides now vastly abandoned) can cause acute intoxications in cattle and sheep.
• Oxfendazole has a certain immunosuppressive effect, particularly in the cellular and humoral phase. It is thought that binding to tubulin affects cell division of the immune cells.
• 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 Oxfendazole Intoxication

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

Pharmacokinetics of Oxfendazole

In ruminants, oxfendazole is slowly but extensively absorbed to the bloodstream: up to 50% of the administered dose is absorbed. The absorption rate strongly depends on the speed of passage through the rumen: the slower the passage, the higher the absorption. 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 or passage into the abomasum (e.g. due to the "oesophageal groove reflex") strongly diminishes the absorption and consequently its efficacy.

Absorbed oxfendazole is well distributed throughout the body, including the lungs and other tissues. Interestingly, absorbed oxfendazole is partly and reversibly reduced to fenbendazole, both in the liver and in the rumen, and vice-versa. However, part of it is irreversibly metabolized to the sulfone derivative that has no anthelmintic efficacy.

In ruminants, parent compound and metabolites are excreted up to 80% through bile and feces, which ensures effective anthelmintic concentration in the gastrointestinal tract for a longer period of time. Excretion through milk is <1% of the administered dose.

Metabolism in cattle and goats is significantly faster than in sheep, which usually requires a higher dose or repeated treatments to achieve the same 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 oxfendazole.

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

Influence of parasites. Heavy infestations with gastrointestinal roundworms reduce the bioavailability of oxfendazole 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 oxfendazole 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. A study in goats showed that an infestation with Ostertagia circumcincta reduced the bioavailability of oxfendazole by ~33%.

Influence of dosing. Splitting the dose in three consecutive daily portions increased the absorption and consequently the bioavailability and the anthelmintic efficacy of oxfendazole in sheep and goats.

Environmental Toxicity of Oxfendazole

• Oxfendazole is moderately toxic to aquatic and terrestrial invertebrates.
• 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 oxfendazole 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.

• Oxfendazole belongs to the chemical class of the benzimidazoles.
• Oxfendazole is moderately used in livestock, but very scarcely in pets.
• Oxfendazole is not used in human medicines.
  
• Oxfendazole is not used in crop pesticides.
• Oxfendazole 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 oxfendazole.