EGATEN (Page 3 of 3)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Mutagenesis

No genotoxic potential was noted for triclabendazole tested in a battery of 6 genotoxicity in vitro and in vivo assays which include a bacterial reverse mutation assay, chromosome aberration assays, and a micronucleus assay.

Impairment of Fertility

No drug-related effects on reproductive performance, mating ratios or fertility indices have been noted in a 2-generation reproductive and developmental toxicity study in rats. The animals were treated with up to 75 ppm triclabendazole via diet, amounting to a mean daily intake of 7.3 mg/kg/day (approximately 0.1 times the MRHD based on body surface area comparison) for a period of 110 days, which included a 12-day mating period beginning on Day 62 of dosing and continuing until the offspring were weaned.

13.2 Animal Toxicology and/or Pharmacology

Dietary administration of triclabendazole at a dose of 39 mg/kg/day (1.1-times the MRHD based on body surface area comparison) was associated with a transient increase in the QT and QTc intervals on weeks 5 and 9 in some dogs in a 13-week study resulting in QT (QTc) intervals of 212-227 (318-338) msec in the 39 mg/kg dose group (adjusted) compared to 190-193 (280-297) msec in controls. At Week 13, no statistically significant differences were noted between the treatment and control groups.

Additionally, when dogs were administered triclabendazole at a single dose of 40 or 100 mg/kg (1.1 or 2.7 times the MRHD based on body surface area comparison), increase in QTc intervals was observed resulting in QTc intervals of 217-247 msec compared to a normal (historical control) of 193-231 msec. However, plasma levels of the sulfone metabolite in dogs (which is thought to mediate QTc prolongation) was about 100-500 times the plasma level of the sulfone metabolite measured in human plasma.

In the 13-week study in beagle dogs, slight anemia accompanied by minimal increases in reticulocyte and nucleated red cell counts were observed at 39 mg/kg/day (1.1 times the MRHD based on body surface area comparison) predominantly at week 9 of dosing.

14 CLINICAL STUDIES

An open label, randomized trial, conducted in Vietnam compared the efficacy of triclabendazole (two 10 mg/kg doses given 12 hours apart with food) to oral artesunate (4 mg/kg, given once daily for 10 days). One hundred patients (age range: 9-74 years) with acute symptomatic fascioliasis were randomized, 50 in each treatment group. At 3 months after treatment, 92% and 76% (difference 16%; 95% CI [1.7, 30.8], p = 0.035) of patients in the triclabendazole and artesunate arms respectively, reported no clinical symptoms.

The clinical development program of triclabendazole for the treatment of fascioliasis included 6 non-randomized, open label studies performed in Cuba, Bolivia, Peru, Chile, and Iran in a total of 245 adult and pediatric patients with stool-confirmed fascioliasis. All studies were similar in design. The studied triclabendazole doses ranged from 5 mg/kg to 20 mg/kg administered on Days 1-3. Cure was defined as absence of Fasciola eggs in the stool based on the Kato-Katz method at Day 60 in patients who were positive at baseline. Across these studies, there was a finding of a dose response. Specifically, the Day 60 cure rate was highest (95.5%; 95% CI [77%, 100%]) for the 20 mg/kg dose, which was given in 2 divided doses, followed by cure rates of 88% (95% CI [64%, 99%]), 80% (95% CI [73%, 86%]), and 50% (95% CI [27%, 73%]) in the 15 mg/kg, 10 mg/kg, and 5 mg/kg dose groups, respectively. The 5 mg/kg, 10 mg/kg, and 15 mg/kg dosing regimens are not approved [see Dosage and Administration (2)]. These rates were significantly higher than that estimated from patients receiving an inadequate, non-triclabendazole treatment in a separate study (22%; 95% CI [9.8, 38.2]).

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

EGATEN (triclabendazole) tablets are supplied as pale red, speckled, capsule shaped, biconvex tablets, with imprint “EG EG” on one side and functionally scored on both sides. Each tablet contains 250 mg of triclabendazole. EGATEN (triclabendazole) tablets are available as:

Blister packs of 4 tablets (NDC 0078-0937-91).

Storage

Store in the original container. Store below 30°C (86°F).

17 PATIENT COUNSELING INFORMATION

Important Administration Instructions

Advise patients that EGATEN should be taken orally with food. The tablets can be swallowed whole or divided in half and taken with water, or crushed and administered with applesauce. The crushed tablet mixed with applesauce is stable for up to 4 hours [see Dosage and Administration (2)].

QT Prolongation

Advise patients with a history of prolongation of the QTc interval or a history of symptoms compatible with a long QT interval or when EGATEN is used in patients who receive drugs that prolong the QT interval that their ECGs will need to be monitored [see Warnings and Precautions (5.1)].

Distributed by:

Novartis Pharmaceuticals Corporation

East Hanover, New Jersey 07936

For more information on EGATEN, call 1-888-669-6682.

© Novartis

T2019-100

PRINCIPAL DISPLAY PANEL

Egaten®

(triclabendazole)
Tablets

250 mg per tablet

NDC 0078-0937-91

Rx only

4 scored tablets

Novartis

PRINCIPAL DISPLAY PANEL
Egaten®
(triclabendazole)
Tablets
250 mg per tablet
NDC 0078-0937-91
Rx only
4 scored tablets
Novartis
(click image for full-size original)
EGATEN
triclabendazole tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0078-0937
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
TRICLABENDAZOLE (TRICLABENDAZOLE) TRICLABENDAZOLE 250 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE MONOHYDRATE
STARCH, CORN
HYMETELLOSE (4150 MPA.S)
MAGNESIUM STEARATE
SILICON DIOXIDE
FERRIC OXIDE RED
Product Characteristics
Color RED (Pale red; Speckled) Score 2 pieces
Shape CAPSULE Size 19mm
Flavor Imprint Code EGEG
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0078-0937-91 4 TABLET in 1 BLISTER PACK None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA208711 02/13/2019
Labeler — Novartis Pharmaceuticals Corporation (002147023)

Revised: 12/2020 Novartis Pharmaceuticals Corporation

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