Triclabendazole 5% · Oral suspension

Triclabendazole is an anthelmintic against Fasciola species [see Microbiology (12.4)].

After oral administration of a single dose of 10 mg/kg triclabendazole with a 560-kcal meal to patients 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.

Absorption — Following oral administration of a single dose of triclabendazole at 10 mg/kg with a 560-kcal meal to patients with fascioliasis, the median Tmax for the parent compound and the sulfoxide metabolite was 3 to 4 hours.

Effect of Food — Cmax and AUC of triclabendazole and sulfoxide metabolite increased approximately 3-fold and 2-fold, respectively, when triclabendazole was administered as a single dose at 10 mg/kg with a meal containing a total of approximately 560 kcal (consisting of 2 cups of sweetened white coffee, a roll with cheese, and a roll with butter and jam). In addition, the sulfoxide metabolite Tmax increased from 2 hours in the fasted state to 4 hours in the fed state.

Distribution — The apparent volume of distribution (Vd) of the sulfoxide metabolite in fed patients is approximately 1 L/kg.

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

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

Metabolism — Based on in vitro studies, triclabendazole is primarily metabolized by CYP1A2 (approximately 64%) into its active sulfoxide metabolite and to a lesser extent by CYP2C9, CYP2C19, CYP2D6, CYP3A, and FMO. This sulfoxide metabolite is further metabolized primarily by CYP2C9 to the active sulfone metabolite and to a lesser extent by CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6 and CYP3A4, in vitro.

Excretion — No excretion data is available in humans. However, in animals, the drug is largely excreted via the biliary tract in the feces (90%), together with the sulfoxide and sulfone metabolite. Less than 10% of an oral dose is excreted in the urine.

Specific Populations — The pharmacokinetics of EGATEN were not studied in patients with renal or hepatic impairment.

Pediatric Patients — No dedicated pediatric pharmacokinetic studies were conducted. However, in one pharmacokinetic study of 20 patients, 7 children (ages 9 to 15 years) were dosed with triclabendazole 10 mg/kg single dose. AUC values of triclabendazole sulfoxide were 20% lower in these pediatric patients in the fed state than in the 13 patients above 15 years of age, but the difference was not statistically significant.

Drug Interaction Studies: — Clinical drug interaction studies have not been conducted for triclabendazole.

In Vitro Studies — Triclabendazole and its sulfoxide and sulfone metabolites have the potential to inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A at clinically relevant plasma concentrations, with the highest potential of inhibition on CYP2C19. No in vitro studies were conducted to assess the ability of triclabendazole and its metabolites to induce CYP enzymes. No in vitro studies were conducted to assess the ability of triclabendazole and its metabolites to induce or inhibit transporters.