Common name: TRICLABENDAZOLE

Type: veterinary medecine
Chemical class: benzimidazole

CHEMICAL STRUCTURE

Molecular structure of TRICLABENDAZOLE 

 


EFFICACY AGAINST PARASITES

Type of action: flukicide anthelmintic, endoparasiticide
Main veterinary parasites controlled: Adult and immature liver flukes

Efficacy against a specific parasite depends on the delivery form and on the dose administered. National regulatory authorities determine whether a product is approved for a given indication, i.e. use on a particular host at a specific dose and against a specific parasite. Check the labels of the products available in your country.

Click here for general information on features and characteristics of PARASITICIDES.


DOSING

Dosing recommendations for antiparasitics depend on national regulations. National regulatory authorities determine whether a product is approved for a given indication, i.e. use on a particular host at a specific dose and against a specific parasite. Check the labels of the products available in your country for specific information on approved indications.

The table below indicates some usual dosing recommendations for triclabendazole issued by manufacturers or documented in the scientific literature. They may not be approved in some countries.

Triclabendazole is a narrow-spectrum benzimidazole with highly flukicidal efficacy. It is not effective against roundworms, tapeworms or most external parasites. It is used abundantly in ruminants mainly as a drench, often mixed with other anthelmintics with nematicidal efficacy (e.g. ivermectin, levamisole, etc.). It is not used in swine, poultry, horses or pets, simply because flukes are usually not an issue for these animals.

Dosing recommendations for TRICLABENDAZOLE
Delivery Parasites Dose (against triclabendazole-susceptible parasites)
CATTLE
Oral Fasciola hepatica, Fasciola gigantica 12 mg/kg
SHEEP & GOATS
Oral Fasciola hepatica, Fasciola gigantica 10 mg/kg
HORSES
Oral Fasciola hepatica 10-12 mg-kg
SOUTHAMERICAN CAMELIDS
Oral Fasciola hepatica, Fasciola gigantica 10-15 mg-kg
DEER
Oral Fascioloides magna 10 mg/kg in the feed during 6-7 days

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SAFETY

Oral LD50, rat, acute*: >8000 mg/kg
Dermal LD50, rat, acute*: > 4000 mg/kg
* These values refer to the active ingredient. Toxicity has to be determined for each formulation as well. Formulations are usually significantly less toxic than the active ingredients.

MRL (maximum residue limit) established for either beef, mutton pork or chicken meat*:

  • CODEX: Yes
  • EU: Yes
  • USA: No
  • AUS: Yes

* This information is an indicator of the acceptance of an active ingredient by the most influential regulatory bodies for use on livestock.

Withholding periods for meat, milk, eggs, etc. depend on delivery form, dose and national regulations. Check the product label in your country.

Learn more about triclabendazole safety (poisoning, intoxication, overdose, antidote, symptoms, etc.).

General information on the safety of veterinary antiparasitics is available in specific articles in this site (click to visit):

WARNING

Never use products for livestock on dogs and cats unless they are explicitly approved for both livestock and pets. Pets may not tolerate livestock formulations

It is obvious that veterinary products are not intended for and should never be used on humans!!!


MARKETING & USAGE

Decade of introduction: 1980
Introduced by: CIBA-GEIGY → NOVARTIS → ELANCO
Some original brands: FASINEX, ENDEX
Patent: Expired (particular formulations may be still patent-protected)

Use in LIVESTOCK: Yes, abundant
Use in HORSES: NO
Use in DOGS and CATS: No

Main delivery forms: 

Use in human medicine: Yes
Use in public/domestic hygiene: No
Use in agriculture: No
Generics available:  Yes, numerous


PARASITE RESISTANCE

In livestock: Yes, reported in several countries (Australia, New Zealand, UK, Ireland, Spain, Argentina, Perú, etc.) in ruminants. MOstly with cross-resistance with albendazole. Not yet as serious as resistance of gastrointestinal roundworms to benzimidazoles.
In dogs and cats: No

Learn more about parasite resistance and how it develops.


SPECIFIC FEATURES

Triclabendazole is a veteran anthelmintic flukicide compound belonging to the chemical class of the benzimidazoles. It is abundantly used on sheep, goats and cattle, mostly in drenches, seldom in the form of tablets, boluses, etc.

It is not used on pig, poultry, dos or cats.

It is often used in mixtures, together with a broad-spectrum nematicide (e.g. abamectin, albendazole, fenbendazole, ivermectin, levamisole) to add efficacy against roundworms.

In 2012 the EU has set an MRL for milk in dairy ruminants. This means that triclabendazole products can be used on dairy animals in the EU respecting the established withholding period.

Triclabendazole is also used as a human medicine against liver flukes.

Efficacy of triclabendazole

Triclabendazole is highly effective against adults of the common liver fluke (Fasciola hepatica) as well as all immature stages, i.e. early immature larvae (1 to 6 weeks old) and immature larvae (6 to 9 weeks old). In fact, it is the only flukicide effective against all early immature liver fluke larvae.

Efficacy against these early immature larvae is important, because these larvae significantly damage the liver tissue when migrating towards the bile ducts.

Triclabendazole is also effective against Fasciola gigantica and Fascioloides magna.

In contrast with most other benzimidazoles, triclabendazole has no efficacy against roundworms or tapeworms.

Triclabendazole has only a limited residual effect. This means that a single administration will kill the parasites present in the host at the time of treatment and protect against re-infestations for a few days, but not for weeks. However, since triclabendazole kills not only the adult flukes but also the immature stages, the treated animals recover more completely and for a longer period of time.

Resistance of liver flukes to triclabendazole (and albendazole) in sheep was already discovered in the mid 1990's in Australia. Since than it has been reported in several other countries (e.g. New Zealand, UK, Ireland, Spain, Argentina), also in cattle. However, the incidence so far is not that serious as for roundworm resistance to benzimidazoles and other nematicides. Nevertheless, in certain regions products with triclabendazole may not protect livestock adequately against liver flukes.

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.

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.

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