WHO Acute Hazard classification: Not listed.

Mechanism of action of Triclabendazole

The molecular mode of action of all benzimidazoles, including triclabendazole, 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.

However, triclabendazole binds to a specific "tubulozole" receptor in the microtubules of flukes, which interferes mainly with the intracellular transport in the cells and not with cell division. For these reason it has no teratogenic effect as other benzimidazoles. Triclabendazole also inhibits protein synthesis in liver flukes, which affects enzyme production and therefore digestion, tegument maintenance, as well as egg and sperm production.

Acute Toxicity and Tolerance of Triclabendazole

• LD50 acute, rats, p.o. >5000 mg/kg
• LD50 acute, rats, dermal >4000 mg/kg
• LD50 acute, rabbits, p.o. 206 mg/kg
• Safety margin
• Cattle: ~15
• Sheep: ~20
• Therapeutic margin: 10 to 20.
• Cattle and sheep tolerate up to 100 mg/kg without toxic symptoms.
• In sheep, single doses >100 mg/kg caused loss of appetite and slightly increased blood levels of urea and alpha-globulins. A single dose of 200 mg/kg caused loss of appetite, transient weight loss and slight motor disturbances. At 50, 100 and 200 mg/kg a slight weight increase of the liver was recorded.
• As a general rule, sheep, goats and cattle tolerate triclabendazole very well.

Toxic Symptoms caused by Triclabendazole Poisoning

• As a general rule, poisoning with triclabendazole 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 the most frequent symptoms are loss of appetite, weight loss and motor disturbances.

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

• There are a few reports on skin irritation at the nose and the udders in cattle after triclabendazole treatment, possibly due to photosensitization.

Antidote and Treatment of Triclabendazole Intoxication

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

Pharmacokinetics of Triclabendazole

Orally administered triclabendazole is well absorbed into the bloodstream. It is quickly oxidized in the liver to its sulfoxide derivative, which is also an effective flukicide. Peak plasma levels of the sulfoxide are reached about 1 day after administration. The sulfoxide itself is further metabolized to the sulfone derivative, which is ineffective. Peak plasma levels of the sulfone are reached 3 days after treatment. These two metabolites are usually detected in tissues and milk, whereas the parent molecule remains almost undetectable. Both metabolites bind strongly to plasma proteins, mainly to albumin. The sulfoxide binds reversibly to albumins, and is partly released back in the liver tissues, which increases its bioavailability and the length of its efficacy.

Excretion is achieved mainly through bile and feces (>90%), urine (~2%), and milk (~1%). About 50% of the administered dose is excreted 6 days after treatment.

In ruminants, the slow passage through the complex stomach prolongs the time it can be absorbed. Direct administration into the abomasum (e.g. due to the "oesophageal groove reflex") strongly diminishes the absorption and consequently its 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 is 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.

Environmental Toxicity of Triclabendazole

• Triclabendazole is highly toxic to fish and moderately toxic to birds.
• 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 livestock triclabendazole 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.

• Triclabendazole belongs to the chemical class of the benzimidazoles.
• Triclabendazole is not used in dogs or cats.
• Triclabendazole is used in human medicines.
  
• Triclabendazole is not used in crop pesticides.
• Triclabendazole 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 triclabendazole.