ic parasitic infection (N = 104)was generally similar to the safety profile in fascioliasis, except for a lower incidence of post-treatmentabdominal pain.
Liver Enzyme Elevations
In clinical studies, up to one third of patients had liver enzyme elevations at baseline, which generally improvedpost-treatment. Of those with normal liver enzyme values at baseline, 6.8%, 4.5%, 4.2% and 3% of patients hadpost-treatment elevations in bilirubin, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and
alanine aminotransferase (ALT), respectively. Transient increases in liver enzymes and total bilirubin infascioliasis patients receiving triclabendazole are reported in the literature.
6.2 Postmarketing Experience
Resistance to triclabendazole has been reported outside the United States [see Microbiology (12.4)].
7 DRUG INTERACTIONS
7.1 Effect of EGATEN on CYP2C19 Substrates
No specific clinical drug interaction studies have been conducted for triclabendazole. However, in vitro datasuggest the potential for increased plasma concentrations of CYP2C19 substrates with concomitant use oftriclabendazole [see Clinical Pharmacology (12.3)]. The potential elevation in concentrations of concomitantlyused CYP2C19 substrates is expected to be transient based on the short elimination half-life and short treatmentduration of triclabendazole.
For those CYP2C19 substrate drugs that require therapeutic monitoring of systemic drug exposures, if theplasma concentrations of the CYP2C19 substrates are elevated during administration of triclabendazole, recheckthe plasma concentration of the CYP2C19 substrates after cessation of triclabendazole therapy.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on EGATEN use in pregnant women to inform a drug-associated risk of major birthdefects, miscarriage or adverse maternal or fetal outcomes. Reproductive studies in animals (rat and rabbits)have not shown a risk of increased fetal abnormalities with exposure to triclabendazole during organogenesis atdoses approximately 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg based onbody surface area comparison (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population are unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. generalpopulation, the estimated background risk of major birth defects and miscarriage in clinically recognizedpregnancies is 2%-4% and 15%-20%, respectively.
Data
Animal Data
Embryo-fetal developmental toxicity studies revealed no malformations in rats and rabbits at doses up to 200mg/kg/day and 20 mg/kg/day, respectively (approximately 1.6 times and 0.3 times the MRHD based on bodysurface area comparison, respectively). The animals were treated orally during organogenesis, starting on Day 6of the pregnancy until Day 15 in rats and Day 18 in rabbits. Maternal toxicity was noted at doses greater than orequal to 100 mg/kg/day in rats and 10 mg/kg/day in rabbits, which was associated with lower fetus weights anddelayed ossification. These findings were considered indicative of delayed physiological growth that wassecondary to maternal toxicity. No increase in malformation or other abnormalities was observed at any doselevel in either species.
8.2 Lactation
Risk Summary
There are no data on the prese |
