Triclabendazole

359.66

359.66

1312995-182-4

4784C8E03O

759250

DTXSID7043952

P - Antiparasitic products, insecticides and repellents

29339900

63.2

5.7

white to brown crystalline powder

1.3875 (rough estimate)

176-178 °C @ Solvent: Ethanol

495.9°C at 760 mmHg

253.7ºC

1.724

0.5 [ug/mL]

0-6°C

Oral-rat LD50: > 8000 mg/kg; Oral-Mouse LC50: > 8000 mg/kg

Flammable; decomposes toxic hydrogen chloride, sulfur oxides, nitrogen oxide gas

179.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|179.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]

3

36/37/38

26-36-24/25

DD6747000

Xi

Warehouse low temperature, ventilated, dry

Stability

P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, P391, P501

H302

|Warning|H373 (92.11%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P314, and P501|Aggregated GHS information provided by 79 companies from 6 notifications to the ECHA C&L Inventory.

practically nontoxic

**Oral LD50 (rat)**: >8 gm/kg; Oral LD50 (mouse): >8 gm/kg[MSDS] **A note on the use in pregnancy** There are no available data on triclabendazole use in pregnant women to calculate a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Reproductive studies in animals (rat and rabbits) have not demonstrated an increased risk of increased fetal abnormalities with exposure to triclabendazole during the organogenesis period at doses which were about 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg. **Carcinogenesis/Mutagenesis** No genotoxic risk was noted for triclabendazole tested in 6 genotoxicity in vitro and in vivo assays. **Impairment of Fertility** No drug-related effects on reproductive performance, mating ratios or indices of fertility have been observed in a 2-generation reproductive and developmental toxicity study in rats. **A note on use in breastfeeding** There are no human findings on the presence of triclabendazole in milk, the effects on a nursing infant, or the effects on maternal milk production. The results of animal studies indicate that triclabendazole is found in goat milk when given as a single dose to a lactating female goat. When a drug is found to be present in animal milk, the likelihood that it will be found in human milk is high. Excercise caution if this drug is administered during nursing.

The published and historic controlled trials of triclabendazole in chronic fascioliasis rarely described adverse event rates or blood test results except for eosinophilia. Instances of enzyme elevations and jaundice have been described, but patients with chronic fascioliasis often have minor elevations in liver tests. Furthermore, the common side effects of treatment are most likely due to the effects of sudden expulsion of the liver flukes from the biliary tree, which can result in transient serum ALT and alkaline phosphatase elevations and even jaundice. There are no reports of serious liver injury, acute liver failure, vanishing bile duct syndrome or chronic hepatitis after triclabendazole therapy. There are reports of cholestatic hepatic injury and vanishing bile duct syndrome linked to other benzimidazole anthelmintic agents such as thiabendazole and albendazole. There is also reported association between Fasciola infection with the potential for bile duct obstruction and sequelae.

Protein-binding of triclabendazole, sulfoxide metabolite and sulfone metabolite in human plasma was 96.7%, 98.4% and 98.8% respectively.

This drug is indicated for the treatment of fascioliasis in patients aged 6 years old and above.|FDA Label

Triclabendazole is an oral anthelmintic used in the treatment of chronic fascioliasis. Triclabendazole therapy is generally well tolerated but can be accompanied by abdominal pain, nausea and mild liver test abnormalities, which are probably due to the expulsion of dead or dying flukes rather than hepatic injury due to the therapy.

Anthelmintic Agents

Triclabendazole and its metabolites are active against both the immature and mature worms of _Fasciola hepatica_ and _Fasciola gigantica_ helminths. **Effect on QT interval** This drug may prolong the cardiac QT interval. Monitor ECG in patients with a history of QT prolongation or who are taking medications known to prolong the QT interval.

Agents used to treat cestode, trematode, or other flatworm infestations in man or animals. (See all compounds classified as Antiplatyhelmintic Agents.)

After a single oral dose of 10 mg/kg triclabendazole with a 560-kcal meal to patients diagnosed with fascioliasis, mean peak plasma concentrations (Cmax) for triclabendazole, the sulfoxide, and sulfone metabolites were 1.16, 38.6, and 2.29 μmol/L, respectively. The area under the curve (AUC) for triclabendazole, the sulfoxide and sulfone metabolites were 5.72, 386, and 30.5 μmol∙h/L, respectively. After the oral administration of a single dose of triclabendazole at 10 mg/kg with a 560 calorie meal to patients with fascioliasis, the median Tmax for the parent compound as well as the active sulfoxide metabolite was 3 to 4 hours. **Effect of Food** Cmax and AUC of triclabendazole and sulfoxide metabolite increased about 2-3 times when triclabendazole was administered as a single dose at 10 mg/kg with a meal containing approximately 560 calories. Additionally, the sulfoxide metabolite Tmax increased from 2 hours in fasting subjects to 4 hours in fed subjects.|No data regarding excretion is available in humans. In animals, triclabendazole is primarily excreted by the biliary tract in the feces (90%), together with the sulfoxide and sulfone metabolite. Less than 10% of an oral dose is found excreted in the urine.|The apparent volume of distribution (Vd) of the sulfoxide metabolite in fed patients is about 1 L/kg.

Based on in vitro studies, triclabendazole is mainly metabolized by CYP1A2 enzyme (approximately 64%) into its active _sulfoxide_ metabolite and to a lesser extent by CYP2C9, CYP2C19, CYP2D6, CYP3A, and FMO (flavin containing monooxygenase). This sulfoxide metabolite is further metabolized mainly by CYP2C9 to the active sulfone metabolite, and to a smaller extent by CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, and CYP3A4, _in vitro_.

The plasma elimination half-life (t1/2) of triclabendazole, the sulfoxide and sulfone metabolites in human is about 8, 14, and 11 hours, respectively.

Triclabendazole is an anthelmintic agent against _Fasciola_ species. The mechanism of action against Fasciola species is not fully understood at this time. In vitro studies and animal studies suggest that triclabendazole and its active metabolites (_sulfoxide_ and _sulfone_) are absorbed by the outer body covering of the immature and mature worms, causing a reduction in the resting membrane potential, the inhibition of tubulin function as well as protein and enzyme synthesis necessary for survival. These metabolic disturbances lead to an inhibition of motility, disruption of the worm outer surface, in addition to the inhibition of spermatogenesis and egg/embryonic cells. **A note on resistance** In vitro studies, in vivo studies, as well as case reports suggest a possibility for the development of resistance to triclabendazole. The mechanism of resistance may be multifactorial and include changes in drug uptake/efflux mechanisms, target molecules, and changes in drug metabolism. The clinical significance of triclabendazole resistance in humans is not yet elucidated.

6-chloro-5-(2,3-dichlorophenoxy)-2-methylthiobenzimidazole

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Veterinary Drug -> ANTHELMINTHIC_AGENT; -> JECFA Functional Classes|Pharmaceuticals

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